Challenge of AIDS

POPULAR SCIENCE

Khorshed

M.Pavri

• :'V:

Popular Science

CHALLENGE OF AIDS KHORSHED M. PAVRI

NATIONAL BOOK TRUST, INDIA

ISBN 81-237-0175-6 First Edition 1992 (Saka 1905) First Reprint 1994 (Saka 1916) First Revised Edition 1994 (Saka 1916) © Khorshed M. Pavri, 1992

Published by the Director, National Book Trust, India A-5 Green Park, New Delhi 110 016 *

Contents Acknowledgemen ts Foreword

vii ix

1.

The Story of AIDS : Introduction

1

2.

How Does HIV/AIDS Spread?

7

3.

The Virus and the Tests

25

Appendix 1

42

4.

Natural History of AIDS

44

5.

The Enigma of AIDS: HIV versus the Immune System

51

6.

How to Survive though HIV-infected

64

7.

Development of AIDS Vaccine

72

8.

Information, Education and Communication/ 82 Counselling (IEC), and, Legal and Ethical Issues

9.

Appendix 2

103

AIDS versus Us, the People of India

105

10. Conclusion, but not the End of the Story

115

Epilogue I

120

Epilogue II

138

Acknowledgements My sincere thanks go to Mr P.R. Dasgupta, Additional Secretary and Project Director of the National AIDS Control Organisation (NACO), for readily sparing his valuable time and writing the Foreword. I am indebted to the Director General of the Indian Council of Medical Research (ICMR), Dr G.V. Satyavati, for her continued support and encouragement to my writing endeavours. I am also grateful to her for permitting the use of some written and photographic material of the ICMR Centre for AIDS Research and Control (CARC). It is a pleasure to express my appreciation to Dr Jeanette Rodrigues, Dr S.V. Apte, Dr R.R. Gangakhedkar and Miss S. Sengupta for valuable suggestions. I am also very grateful to Dr R.S. Kamat for his helpful suggestions on some aspects of immunology. My profound appreciation to my colleagues, Mrs Veena Kadkol and Mr Sunil More, for their willing help to organise the final manuscript, including many tedious details. I also thank Mrs Neeta Surve for her patient and painstaking typing of several drafts. Finally, I must thank the National Book Trust (NBT) for giving me this opportunity; indeed, this book could not have been a reality without their suggestion that I write one. My temerity in accepting the task owes much to the encouragement received from Ms Manju Gupta, Assistant Editor, NBT, and the guidance from Dr G.P. Phondke, Director of the Publications and Information Directorate.

Vf

I

I: *

Foreword It has been aptly stated that when the history of public health during the last 50 years is recorded by chroniclers, it will indicate a great triumph and a terrible tragedy. The triumph relates to the elimination of small-pox and the tragedy to the holocaust of AIDS. Within a span of 13 years since its emergence in 1981, we have now an estimated number of over 15 million HIV-infected men, women and children all over the world. It has now spread to almost all the countries in the world and made popular a new word in the public health lexicon—'pandemic'. The continued spread of HIV is not only threatening many millions of lives, but is also slowing, and in some cases reversing, progress made in social and economic development. We in India are not immune from this threat. In her eminently readable book called Challenge of AIDS, Dr Khorshed Pavri has unfolded the various facets of this tragic and fascinating phenomenon. She is well known in the scientific circle for her significant contribution to generate enlightened awareness about HIV/AIDS in India. She writes with knowledge, conviction and authority. There is a need to demystify AIDS and talk about it in a dispassionate and non-judgmental way. I think Dr Pavri's book will be a positive step towards that direction. The fact that the revised edition is coming out soon after its initial publication shows that this hope is not misplaced. New Delhi

8 June, 1994

P.R. DASGUPTA

1

THE STORY OF AIDS : INTRODUCTION Tracing the history of AIDS is like unravelling a mystery story. This story also begins with "A long time ago, there existed an agent which came to light only in the 1980s." AIDS—acquired immune deficiency syndrome—is a condition in which the in-built defence systems of the body break down completely. This phenomenon is gradual, but ultimately leads to total depletion of a very important cell component of the immune mechanism. Those affected are thus unable to combat commonly known diseases like pneumonias, diarrhoeas, tuberculosis (TB) and even common colds; ultimately, they die due to one or another of these infections (Fig. 1). Because of the varied nature of these diseases, called 'AIDS associated', 'AIDS related' or 'AIDS indicator diseases' (including cancers), AIDS has been identified as a syndrome rather than a single clinical entity. This means that AIDS patients show several signs1 and symptoms 2 which occur together at the same time. AIDS was recognized for the first time in the USA in 1981. At that time, it was mainly associated with either of the two major indicator diseases : (1) an unusual type of pneumonia caused by a protozoan parasite, Pneumocystis carinii, and (ii) a cancer mainly of the skin called Kaposi's sarcoma, which was rarely seen in people under 60 before the advent of AIDS. These diseases, with various 1 2

Objective evidence of a disease that can be observed by a doctor. Complaints—physical or mental—reported by the patient.

2

.

CHALLENGE OF AIDS

- IMMUNITY IS KNOCKED OUT. - 80DY RESISTANCE IS REDUCED SO THAT EVEN MILD INFECTIONS CANNOT BE OVERCOME : SKIN DISEASES, T.B , PNEUMONIAS, DIARRHOEAS AND EVEN CANCERS FLARE UP-AND ULTIMATELY, THE INEVITABLE END. Fig. 1 : We all have to die some day, but don't die of AIDS due to ignorance.

combinations of other common infections, were first noted in young and active men who had been otherwise quite healthy. All of them shared a sexual lifestyle that was different; they were men who had sex exclusively with men. In other words, these men were homosexuals, colloquially called 'gays'. Since the syndrome was first recognized in them not only in the USA but subsequently in Europe and Australia, it was called gay related immunodeficiency or GRID. A little later, cases of AIDS were identified among drug addicts, especially intravenous drug users (IVDU). Most of those found to be affected with AIDS started dying and thus the peculiar combination of sex and death attracted great attention and gave rise to many myths and misconceptions. Earlier also, civilizations had witnessed devastating

THE STORY OF AIDS : INTRODUCTION

3

global epidemics or pandemics: for example, bubonic plague in the 18th century and the Spanish 'flu' in the 19th century which had globally killed millions of people within a short period. AIDS however appeared to be different. AIDS also killed those affected surely though slowly. But, because of the early stamp of homosexuality and IV drug use among those who died, the patients with AIDS (PWAs) were not called AIDS patients (like cancer patients) but were termed victims. This word implied a kind of helplessness; a feeling that these patients were being sacrificed due to some ritual performed by them or under other such conditions. Perhaps, the word 'victim' was applied to show that these persons were sacrificed because of the 'wrath of God'. Soon enough, however, there came to light another group of AIDS patients who had no peculiar lifestyle or risk behaviour. This group consisted of persons (children and adults) who had received transfusion of blood or blood products. When more and more women got AIDS, it was found that children born of these women developed AIDS. All these persons were also identified as victims, but now, they were qualified as 'innocent' victims so as to discriminate between the 'guilty' ones. It is best to avoid such a negative moralistic approach which imparts a sense of helplessness to patients with AIDS. With the widening of people 'at risk' of contracting AIDS and also involvement of many countries of all the continents, the earlier complacency gave way to panic. Panic, because although it was already recognized by scientists that some infectious agent could be responsible, there was no known measure available for stopping further spread of this yet unidentified agent. Discovery of the Causative Agent The major ingredients in solving a mystery is to find out who are affected, and also, how and why. After this, one

4

.

CHALLENGE OF AIDS

can pin down what caused the event, i.e. the entity responsible for the mysterious event. It was, perhaps, fortunate that AIDS occurred during the initial phase in the economically developed industrialized countries like the USA, France and other countries in western Europe. The much needed infrastructure and expertise already existed in these countries. The result was that several questions pertaining to who were affected, why and how could soon be answered partially, if not fully. After many attempts to incriminate several known agents, scientists realized that the infectious agent mainly responsible for AIDS must be a virus that might be 'new' to science. The syndrome was recognized in 1981, and by 1983, scientists in France discovered the AIDS virus and showed that it was indeed 'new'. In 1984, virologists from the US also published their report revealing a virus to be the causative agent. At first, different names were given to the AIDS virus by the French and the American workers, and there were great differences of opinions and debates regarding the question of priority Box 1 French-US Agreement and Constitution of World AIDS Foundation The World AIDS Foundation (WAF), incorporated under the laws of Switzerland, was established in December 1988. Under the agreement between the Department of Health and Human Services of USA and the Institut Pasteur of France, WAF grants funds for the support of research and education relating to AIDS in the developing world. The money for grants comes from the royalties collected from sales of test-kits for HIV manufactured either within France or USA or employing their respective viral material. Very recently, in July 1994, a new agreement has been made conceding larger amounts to the French side. The WAF receives 25 per cent of the total of a pool of about 80 per cent of the combined royalties.

THE STORY OF AIDS : INTRODUCTION

5

between the two nations. Ultimately, the International Committee on the Nomenclature of Viruses intervened and the name human immunodeficiency virus or HIV was accepted. However, the controversy regarding whose virus was used in the manufacture of diagnostic reagents and such other issues of patent rights have not totally subsided (Box 1). Recognition of AIDS as a new disease does not mean it was entirely a new syndrome. In fact, immunodeficiencies of three types had been recognized earlier (Fig. 2). Genetic or hereditary deficiency is passed on from parents to the newborn in the form of a defective gene. This does not allow the full complement of immune mechanism to function in these persons. The second type is that induced by doctors, in certain circumstances. For example, before transplanting organs such as kidneys, doctors

Fig. 2 : The three types of immunodeficiency.

6

.

CHALLENGE OF AIDS

deliberately induce immunodeficiency so as to prevent the recipients from rejecting the transplants. In addition to the genetic or hereditary one and that induced by doctors, the third or acquired immunodeficiency was also known to exist earlier. Indeed, it was especially recognized in African countries and other tropical, economically developing countries in Asia, including India. These were, however, mostly attributed to old diseases caused by parasites, compounded further by nutritional deficiencies (including malnutrition), all of which are commonly encountered in these countries. AIDS, as identified in 1981 in the USA, was caused by a newly recognized retrovirus called HIV and therefore it was different. The fact that evidence of HIV infection was not obtained much earlier, imparted its own distinction of newness to AIDS. Suggestions and ideas on where the AIDS virus could have originated first have led to a raging controversy including allegations of racism. Hypotheses ranging from absurd to plausible have been put forth indicating probable involvement of retrovirus(es) of animals, particularly monkeys. 3 Among the various attacks and counterattacks, words of wisdom had been spoken by some in an attempt to diffuse the situation. Among the most relevant ones are the words of Kenneth Kuanda, the then President of Zambia, who had already lost one son to AIDS. He stated : "What is more important than knowing where this disease came from is where it is going."

3

See Epilogue I.

17

H O W DOES HIV/AIDS SPREAD? The word epidemic is generally applied to an infectious disease which affects many individuals around the same time at a certain place. The time and the place are the most important determinants. If an epidemic of the same disease is seen almost all over the world, then it becomes a pandemic; for example, the occurrence of pandemic influenza around the world at the same time. AIDS was recognized first in the USA and Africa and subsequently in most industrially developed and developing countries of the world. No country of the world seems to be free of it. AIDS has indeed established a pandemic situation. Epidemiological studies to understand the why and how of the AIDS pandemic are important. A correct understanding of the evolution of an epidemic situation in a particular region is generally expected to help in formulating measures for prevention. Epidemiology has contributed significantly and is currently contributing substantially to the knowledge of HIV and AIDS. As a matter of fact, within the first 18 months—a full year before AIDS virus was recognized as the cause—and, two years before HIV tests became available, epidemiological investigations led to several beneficial public health measures. Those at high risk of AIDS, called risk groups, were recognized; routes of the disease spread were identified and even recommendations were made to reduce risks by behaviour changes. As a first step to determine how an epidemic develops or is evolving, it is crucial to define the disease under

8

.

CHALLENGE OF AIDS

investigation. As defined by the Centres for Disease Control and Prevention (CDC) of the USA: "AIDS is a disabling or life-threatening illness caused by human immunodeficiency virus (HIV) characterized by HIV encephalopathy, HIV wasting syndrome, or certain diseases due to immunodeficiency in a person with laboratory evidence for HIV infection or without certain other (known) causes of immunodeficiency." (These other causes have been mentioned in Ch. 1 & 5). The emphasis was thus placed on associated diseases which help to identify a patient with AIDS. In 1987, the definition was revised by expanding this list and including many more diseases as indicators of AIDS. Within a few years, however, doctors realized that many other infections such as those causing gynaecological problems in women should also be included. In fact, at one point of time or another, infections associated with many different systems of the body are likely to occur. Incubation Period The virus of AIDS, called human immunodeficiency virus (HIV), infects persons but does not produce illness for a

Fig. 3 : Generally about eight to ten years after exposure to AIDS virus, the person may begin to show signs and symptoms of illness and consult a doctor for treatment.

HOW DOES HIV/AIDS SPREAD ?

9

very long time. This time interval between the exposure to virus (HIV infection) and the manifestation of the disease syndrome, i.e. AIDS, is called the incubation period (Fig. 3). HIV-infected persons generally remain overtly healthy during this period although they may harbour

Stages of HIV Infection Infection with HIV

Development of AIDS

Develop

g- 4 : If infected with HIV, 100 people can expect to progress like this over one year. Reproduced from Talking AIDS: A Guide for Community Work by Gill Gardon and Tony Klouda, published by International Planned Parenthood Federation (IPPF), Sept. 1988. Fl

10

.

CHALLENGE OF AIDS

the virus in the blood. They, in fact, act as carriers of HIV and can infect others. The average incubation period is estimated to be around eight to ten years for adults. It is generally much shorter, around 18 to 24 months for children. When we speak of HIV, it would generally mean infection without disease. It is estimated that about 50 per cent of infected adults will develop AIDS within ten years of exposure to HIV. Ultimately, however, majority of the infected adults will progress to AIDS. The ratio between the numbers of HIV-infected persons and AIDS cases gives an idea of when the virus might have been introduced in a country. A high ratio generally indicates an early stage of the epidemic, that is preponderance of HIV-infected persons who have not yet progressed to AIDS (Fig. 4). How HIV Spreads HIV is an infectious disease but is not easily transmitted through the environment, e.g. from air, water, food, etc. Thus it is not a communicable disease like common cold, influenza, measles or polio viruses and other infectious agents. The virus enters the body in three major modes (Fig. 5). The most important mode is having sexual intercourse with an infected person. The virus can be transmitted from men to men, men to women and to a slightly lower extent (two to five times less) from women to men. The virus transmission is facilitated when either partner has other sexually transmitted diseases (STDs). Genital ulcers and other infections such as syphilis could act as co-factors, aiding and abetting the AIDS virus. The second mode is through transfusion of HIV-infected blood or blood products or through infected blood in needles, syringes and other such instruments. These include needles and syringes shared by intravenous drug users and those which might be reused by doctors/ nurses for injections without proper cleaning and

HOW DOES HIV/AIDS SPREAD ?

11

Fig. 5 : The different modes by which the virus enters the body.

sterilization. The third way is the transmission from an infected mother to her newborn. Although HIV has been detected in several body fluids, it is infectious mainly from blood, semen and vaginal secretions (Box 2). For instance, very few virus particles have been detected (even by sensitive techniques) in saliva, tears and breast milk. Since an infant can consume

12

. CHALLENGE OF AIDS

Box 2 How do we get the virus or are exposed to the virus-containing material? •

The virus is present is blood and body fluids such as male and female sexual fluids (i.e. semen and vaginal secretions) which can transmit it to others.

#

It is also present in saliva and tears but transmission from these have not been documented; perhaps, because the virus in not present in sufficient amounts to infect.

about 800 ml to one litre of breast milk per day, there are chances that it might get infected through this route. However, various advantages of breast milk which make an ideal baby food should be weighed against this small chance of transmission. In any event, saliva and tears are not consumed in such large quantities and thus are not considered likely to spread the virus of AIDS. Just as important, or perhaps even more important, is to know how the virus does not spread among people. The fact that HIV cannot enter the body through most of our normal activities are emphasized in Fig. 6. Among these are included hugging, kissing, eating, drinking, swimming, working and travelling together. One question often asked by people is whether AIDS virus can be transmitted through bites of mosquitoes and other insects. Fortunately, experiments by artificially infected mosquitoes showed that unlike the malaria parasite or dengue virus, HIV has neither a life-cycle nor does it multiply in mosquitoes. The doubt that mosquitoes may take blood of an HIV-infected person and may act like a 'flying needle' has also been removed on epidemiological grounds. Studies in a large number of households of PWAs or HIV-infected persons in Africa revealed that transmission to an uninfected person occurred only through sexual partners. Children and other adults in the households

HOW DOES HIV/AIDS SPREAD ?

13

Fig. 6 : You do not get AIDS through most of the normal activities shown above.

remained free of HIV, despite having casual contacts with HIV/AIDS patients and despite the large number of mosquitoes in the environment. Persons at High Risk of Contracting AIDS From the above it should be clear that only certain situations are likely to facilitate the spread of AIDS virus. Most important among these are those with risky lifestyles or risk behaviours, e.g. female prostitutes (nowadays termed commercial sex workers), male homosexuals and, of course, the people who have sex with multiple

14

.

CHALLENGE OF AIDS

partners including strangers, whether male or female. The reason is that whilst even a single sexual encounter with an HIV-infected person may transmit the virus, chances of transmission increase with the frequency of sexual intercourse with many. All the above-mentioned groups of people with a promiscuous lifestyle were called high risk groups, but this term is not applicable to recipients of blood and blood products. In general, therefore, the term high risk situation should be preferred. Scientists from the World Health Organization (WHO), particularly those in the gobal programme on AIDS (GPA), have been active in compiling and disseminating global information. As a part of the programme, they had determined efficiency of different modes of transmission and the percentage of AIDS cases recorded in the world for the respective mode. The data summarized in Table 1 reveal blood transfusion to be the most effective (more than 90 per cent) and sexual intercourse to be much less so. However, the proportion of AIDS cases was much higher for heterosexual transmission because it is a natural everyday event as compared to blood transfusion. Unfortunately, among the recipients of transfusion are highly vulnerable individuals who have to depend on

HOW DOES HIV/AIDS SPREAD ?

15

continued administration of certain blood products throughout their lives. These are people with hereditary diseases such as thalassaemia and haemophilia. Because of the frequent administration of the required blood products, they face a risk situation on receipt of infected blood products. The risk is reduced, if not totally eliminated, if manufacturers follow standard good practices laid down for the manufacture of blood products. Babies of HIVinfected mothers also face a high risk situation. HIV infection is not transmitted to all infants of the infected mothers; it is estimated to be passed to about 20 to 40 per cent of infants. No definitive study has been carried out in India so far, but the number of HIV-infected mothers is increasing. Global Patterns of HIV Infection Epidemiological studies carried out during the early period of AIDS indicated three broad geographical patterns of HIV in the world, as shown in Table 2. India falls into Pattern III countries where the virus was introduced or began to spread much later (almost a decade later) than in the countries of Patterns I and II. Developments which occurred since then indicate that except for this initial delay in spread, India on the whole seems to follow the Pattern II countries. In the earlier stages, it looked as if a particular concentration of AIDS cases occurred among the moneyed, the urbanized 'upward' community. This feature was clear in the Western world where homosexuals were mainly involved. Even in African countries, where the heterosexual mode of spread was most common, this socioeconomic and urban-rural difference had been commented upon. Later, however, minorities and particularly the poor communities with low levels of education were increasingly recognized to be affected in the developed world. In fact, the current trend is stabilization of the

16

.

CHALLENGE OF AIDS

Table 2 Global Patterns of HIV Infection Pattern I:

Extensive spread of HIV began in the late 1970s/early 1980s. Homosexual males and IV drug users have been the predominantly affected populations, but heterosexual transmission is increasing. Western Europe, North America, some areas in South America, Australia, New Zealand.

Pattern II:

Extensive spread of HIV began in the mid-to-late 1970s/ early 1980s. Heterosexual transmission has and continues to predominate. Africa, Caribbean, some areas in South America.

Pattern III:

Introduction a n d / o r extensive spread of HIV did not occur until mid-to-late 1980s. Extensive spread of HIV is now being documented in several countries in SouthEast Asia, but the prevalence of HIV, in most countries classified within this pattern, remains relatively low. Countries in Asia are included in Pattern III, where HIV was introduced late. Although the number of cases of AIDS in India is low (around 215); it is likely to increase very fast in the near future. Asia, the Pacific region (minus Australia and New Zealand), the Middle East, eastern Europe, some rural areas of South America.

spread of HIV/AIDS among the risk groups first to be recognized, with a rapidly rising spread in the latter. In the Pattern II countries, especially in Sub-Saharan Africa, AIDS and HIV infection are increasingly being recognized in remote rural areas also. In the present global context when a commercial soft drink or a bath soap can reach isolated villages, the presence of infectious agents like viruses should not cause any surprise. Evolution of HIV/AIDS Epidemic in India Like most countries in Asia, India is included in the Pattern III distribution of HIV disease. In April 1986, for the first

HOW DOES HIV/AIDS SPREAD ?

17

time, HIV seropositivity was recorded among ten female prostitutes in Tamil Nadu. Important landmarks of AIDS/ Table 3 Important Landmarks of HIV Disease in India Period

Event

April 1986 : May 1986

:

Dec. 1986

:

July 1987

:

July 1987

:

Oct. 1987

:

April 1988 : Jan. 1989 onward

: :

July 1989

:

Jan.-Feb. 1990

:

Jan.-Feb. 1990

:

Jan. 1989 to date July 1992

:

Oct. 1992

:

:

First cluster (ten prostitutes) of HIV seropositives detected in Madras, Tamil Nadu. First patient of final stage disease detected in Bombay, Maharashtra (recipient of unscreened blood transfusion during cardiac surgery in USA). First seropositive male detected from STD clinic in Tamil Nadu. First seropositive blood donor in Vellore, Tamil Nadu (retrospective detection subsequent to the recipient's illness). Also spouse to spouse transmission (the same donor's wife). Detection of a seropositive infant (born to the abovementioned parents). First indigenous case of full-blown HIV disease in an Indian. Evidence of HIV antibodies in indigenously produced blood products. Evidence of exposure to HIV among a high proportion of donors used by commercial manufacturers followed by a government ban on production. Government gazette notification for mandatory screening of blood donors for freedom from HIV antibodies. Recognition of a cluster of seropositives in IV drug users in north-east India. We may also add Important issues concerning hospital practices arising out of an incident of embalming a body of a patient of HIV disease. Emergence of a highly responsible press on the AIDS scene in India. Constitution of the National AIDS Control Organization (NACO); at state levels also. Establishment of the National AIDS Research Institute, Pune by Indian Council of Medical Research (ICMR).

18

.

CHALLENGE OF AIDS

HIV in India are presented in Table 3. Although late to begin, within five to six years all the known modes of viral spread have been identified. In early 1990, an explosive epidemic of HIV in north-eastern states of India was recognized among thousands of intravenous drug users. The virus might have started late, but is racing rapidly to create a large-scale epidemic situation, especially in some metropolitan cities of our country. Ours was among the few countries which started surveillance to detect HIV infection at a time when the number of AIDS cases was very low. However, because of complacency and lack of implementation, the cost effective strategy of sero-surveillance followed by education and intervention programmes directed only to those at high risk situation never took off. Yet another landmark, selective introduction of 'mandatory screening' of blood donors, was also carried out too erratically to be meaningful. The latest landmarks are the constitution of the National AIDS Control Organization (NACO) as also the state level boards; and the establishment by the ICMR of the National AIDS Research Institute (NARI) at Pune. AIDS Cases in India A case was reported in May 1986 as shown in Table 3. The source of infection was traced to blood transfusion during a coronary bypass surgery in the USA, prior to the introduction of HIV screening in that country. The second case was associated with a blood product given to a haemophilic patient, again in the USA. This, and the fact that some more cases of AIDS were recognized in foreigners at the time, led to some complacency arising out of a misconception. AIDS was considered as a 'foreign' or 'their' disease, not likely to affect 'us' Indians. Soon, however, AIDS began to be recognized among Indians exposed to risk situations in India. For instance, in January 1990, there were 12 cases in foreigners and 32

HOW DOES HIV/AIDS SPREAD ?

19

amongst Indians; chances of missing AIDS among the former were much less. After more than two years, i.e. in early 1992, only one more case was added to the foreigners' category while the number of AIDS cases in India had more than tripled. What is more worrisome is the fact that an overwhelming majority of AIDS patients have been between 20 to 40 years of age. They are the most productive group, economically and reproductively, a fact which imparts an extraordinary significance to AIDS. The cases of AIDS officially recorded by 1994 are presented in Table 4. Table 4 AIDS Cases in India (data as on 31 August 1994)

Indian Foreigner Total

Male 608 14

Female 195 4

Total 803 18

622

199

821

Probable Sources of Infection in India In India

Abroad

Heterosexual promiscuity Homosexual contact Spouse of AIDS patient/ seropositive person Blood transfusion Blood product infusion Intravenous drug addict

563 9

35 1

20 90 7 64

0 3 1 10

Total

753

50

"Information received from Dr Shiv Lai, Additional Project Director (Tech.), National AIDS Control Organization (NACO), Government of India.

The statewise distribution of the cases is shown in the map in Fig. 7. The official figures may, however, not represent the actual number of cases in different states. For example, the highest number of cases recorded in

20

.

CHALLENGE OF AIDS

Fig. 7 : Statewise distribution of AIDS cases in India (31 August,1994).

HOW DOES HIV/AIDS SPREAD ?

21

Maharashtra could, at least in part, reflect the high level of awareness of AIDS among the concerned medical and public health workers. In contrast, no case being recorded from large states like Bihar and Orissa and only one each from Rajasthan and Andhra Pradesh could also be in part due to the lack of such awareness. Indeed, it is difficult to estimate whether only 5 to 10 per cent of the actual cases are officially recorded or only one to two per cent since AIDS is not a notifiable disease. HIV-infected but Otherwise Healthy Persons By the end of August 1994, a total of 21,15,794 persons were screened and 15,562 (7.35/1,000) were confirmed to be HIV-infected (Table 5). Of these, the largest number was in persons having multiple heterosexual partners. A substantial number of blood donors and IV drug users were also seropositive. However, in the absence of the Table 5 Details of Seropositive Individuals Detected Number of persons screened Number of persons seropositive Seropositivity rate (per thousand)

2115794 15562 7.35

Break-up of Seropositives Category Heterosexually promiscuous Homosexuals Blood donors Dialysis patients Antenatal mothers Recipient of blood/blood product Suspected AIDS cases IV drug users Others Total

Seropositives

% of total

6541 42 2494 130 77 326 782 2036 3134

42.03 0.27 16.02 0.84 0.49 2.09 5.67 13.01 20.13

15562

100.00

22

.

CHALLENGE OF AIDS

total numbers of individuals tested from each category, it is difficult to interpret these data. Homosexuality, especially sodomy being a cognizable offence in India, the extent of men having sex with men is not known. It is generally believed that about four to five per cent of men between 15 to 50 years of age might be homosexual. In actual number, this figure is certainly not insignificant. Limited surveys in Bombay show that about four to five per cent of male homosexuals are HIV infected. Official and unofficial reports point to Bombay, Pune and many districts in Maharashtra to be most affected. The most frightening feature of this epidemic is its imminent occurrence among infants born of HIV-infected mothers. Nearly one per 1,000 females tested in antenatal clinics had been found to be infected. These females came from ordinary, middle-class families in Bombay and were not supposed to have any known risk behaviour. Geographic Distribution and the Spread of HIV According to Dr Shiv Lai from NACO, three major epicentres of HIV infection have been identified in the country. These are Bombay, Madras and Imphal. From Bombay and Madras, the infection is spreading through migrant workers, truck drivers and paid blood donors to many other areas. Multi-partner heterosexual lifestyle is the major culprit in the spread. Imphal, in Manipur is responsible for spreading infection through contaminated needles and syringes which are shared by drug users. The easy availability of a pure form of (white) heroin from the notorious 'golden triangle' through Myanmar (Burma) border is mainly responsible for the spread. The different ways in which infected men can spread the virus are shown in Fig. 8. They are much more likely to spread the infection than infected women, both due to biological differences as well as frequency of and variety

HOW DOES HIV/AIDS SPREAD ?

23

24

.

CHALLENGE OF AIDS

in the modes of transmission. For example, a single infected migrant worker can pass the virus to several prostitutes/call girls, by donating blood (if not screened effectively) and also to his wife in rural area and ultimately to his unborn child. Three Faces of Epidemic In conclusion, there are at least three faces to the epidemic of AIDS. The first is the spread of HIV. It should be emphasized that the epidemic of HIV is evolving in an explosive, almost exponential manner. This means that two HIV-infected persons may lead to four, 16, 256, 65536 and so on. The second epidemic is the development of AIDS and patients presenting to doctors and hospitals with various disease manifestations. Because of the long incubation period, there is a long time interval between the appearance of the first (HIV) and the second (AIDS) faces of the epidemic. There is, however, no doubt of a spurt of AIDS cases in India. At the end of 1992, there were 116 AIDS cases recorded whereas by mid 1994 this number has risen sixfold and more to reach 728. This rise cannot be attributed completely to the greater awareness. Perhaps, the most tragic face is the third one; that of stigmatization and discrimination posing the threat to human rights. This face has also started in our country leading some individuals even to commit suicide. This third face which overlaps the first two epidemics will be discussed later.

35

THE VIRUS AND THE TESTS What are Viruses? Viruses are the tiniest living beings recognized so far. They are too small to be seen under an ordinary microscope. Fig. 9 gives an idea of the comparative smallness of the viruses. They can only be visualized after extremely high magnification, made possible with an electron microscope. Viruses are called filtrable, because they can pass through special filters which are used to keep away small germs, such as bacteria. In contrast to other living organisms including bacteria—commonly called germs—viruses possess only one type of nucleic acid, namely deoxyribo nucleic acid (DNA) or ribonucleic acid (RNA). Normally, the genetic (hereditary) information is passed from DNA (the basic genetic material in a cell) to the RNA, which serves as an intermediate for the manufacture of proteins. Proteins are essential for survival as they are ultimately responsible for all functions performed by a living cell and thus a whole organism. Having only one nucleic acid, viruses have evolved to use the machinery of the host cells which they infect. One can almost say that they hijack certain cellular mechanisms for their own purpose of replication (multiplication). Unable to have a free, independent existence, they are the 'true' parasites at the genetic level. In nature, viruses infect almost all living beings, including plants,

26

.

CHALLENGE OF AIDS

Fig. 9 a : Sizes of some common viruses in comparison with a bacterium and a human red blood cell. Figure shows the preparation of blood smear and procedure to observe the red blood cells under the microscope.

animals, and, even bacteria. They can be propagated in a laboratory only in living intact plants/animals or in the cells grown in tubes or flasks (in vitro cell cultures). The animals or their cells need to be susceptible in order to permit viruses to grow. The cells may be called permissive cells.

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Fig. 9 b : The viruses are indeed so tiny that they cannot even be seen under the highest power of an ordinary microscope. Scientists have invented a special microscope, called electron microscope, for visualizing them.

Retroviruses : HIV belongs to the family Retroviridae which has three sub-families (Table 6); retro means 'back', 'in reverse direction'. It applies to the one backward step taken by all retroviruses. They are all RNA viruses, but are able to convert RNA into DNA, the basic genetic material. They do this with the help of a unique enzyme, called reverse transcriptase, which is RNA-dependent DNA polymerase. In contrast, other RNA virus families make proteins directly from their own RNA, helped by permissive cells. Oncoviruses : Cancer causing viruses constitute the largest sub-family having members affecting all vertebrate species. During 1980-1981, Dr Robert Gallo and colleagues

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Table 6 Retroviruses Oncoviruses or transforming viruses (causing cancer)

Spumaviruses or foamy viruses

Lentiviruses or slow viruses

Rous sarcoma virus (chickens) FeLV (feline leukaemia virus) BLV (bovine leukaemia virus) HTLV-I (human T-leukaemia virus, Type I) HTLV-II (human T-leukaemia virus, Type-II) SFV (simian foamy virus) BSV (bovine syncytial virus) FCFV (feline syncytium-forming virus) HNPCV (human nasopharyngeal carcinoma virus) EIAV (equine infectious anaemia virus) CAEV (caprine arthritis encephalitis virus) Visna/Maedi virus (in sheep) BIV (bovine i m m u n o d e f i c i e n c y virus) FIV (feline immunodeficiency virus) HIV (human immunodeficiency virus) SIV (simian immunodeficiency virus)

from the USA isolated and characterized the first human oncovirus (retrovirus) and named it T cell lymphoma/ leukaemia virus (HTLV). Later, they identified yet another similar virus and called these as HTLV-I and HTLV-II. Spumaviruses : These are not yet associated with diseases of men or animals. They only cause a foamy effect in cell cultures grown in test-tubes. Lentiviruses : These are the classic slow viruses recognized in many animal species. They are highly speciesspecific in nature and are transmissible only to closely

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related species. They have been known to play a prolonged game of hide-and-seek with the immune system of the infected hosts, leading to a slowly developing multisystem disease. Human Immunodeficiency Virus (HIV) and Related Lentiviruses HIV was first discovered by Barre' Sinoussi, Montagnier and colleagues at the Institut Pasteur, Paris, in 1983. It was named lymphadenopathy associated virus (LAV). In 1984, Popovic, Gallo and co-workers established cell lines (cells grown in tubes or flasks) which could be permanently infected with their (at least they thought so at the time) isolate of AIDS virus. Keeping in mind the only known human retroviruses (HTLV-I and HTLV-II), they named the new virus as HTLV-III. For a long time thereafter, the virus of AIDS was identified by a long and rather awkward nomenclature: lymphadenopathy associated virus (LAV)/ human T lymphotropic virus-III (HTLV-III). Controversy about the name was finally settled by the International Committee for Nomenclature of Viruses. The virus was recognized as a lentivirus and was given the name of human immunodeficiency virus (HIV). The virus seems to have emerged from the unknown, but has now made itself known all over the world. There have been many speculations regarding the origin of the virus but nothing definite has yet been established (.Epilogue I). In 1985, a different though related virus, called HIV-2, was isolated in France (obtained in a laboratory) from a Portuguese man suffering from AIDS. The first type, HIV-1 is prevalent in most of the industrialized Western world, including Australia and New Zealand and also in Asia, Americas and central Africa. HIV-2 has been recognized mainly in the countries of western Africa. Recently, however, some serological evidence of the activity of HIV-2 has been recorded in many countries

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including India (especially in the Bombay-Pune region). However, HIV-2 has not yet been isolated from India whilst there have been several records of isolation of HIV-1. Among the related lentiviruses are those isolated from horses, sheep, cattle, cats, and monkeys (Table 6). The ones from monkeys, called simian immunodeficiency viruses

Fig. 10 : HIV-1 VIRION, or virus particle, is a sphere that is roughly 130 to 200 nm across. The particle is covered by a membrane made up of two layers of lipid (fatty) material, that is derived from the outer membrane of the host cell. Studding the membrane are glycoproteins (proteins with sugar chains attached). Each glycoprotein has two components: gp41 spans the membrane, and gpl20 extends beyond it. The membrane-and-protein envelope covers a core made up of proteins designated p24 and p (17) 18. The viral RNA is carried in the core, alongwith several copies of the enzyme reverse transcriptase, which catalyses the assembly of the viral DNA.

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(SlVs), are most closely related to HTV, particularly HIV-2, though they appear to be more distant relatives of HIV1 (Epilogue I). Viral Structure and Morphology The structural model of HIV (Fig. 10) reveals it to be a sphere containing RNA as its genetic material. Morphologically, HIV is classified as lentivirus according to the manner in which they bud from the cell membrane. Highly magnified AIDS virus on a human T-helper cell is shown in Fig. 11. HIV has a very complex genome. It is even more complicated than that of other known retroviruses. The eight to ten genes express structural and regulatory proteins. The former constitute the viral structure. The major internal structural protein has a molecular weight of 24,000

Fig- 11 : Highly magnified HIV-1 on a T-helper cell.

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and is called p24 (Fig. 10). The p l 7 (pl8) core protein covers the internal surface of the envelope. The envelope is a two-layered lipid or fatty coat. The lipid material is derived from the outer membrane of the host cell acquired during the budding process. The envelope proteins have attached sugar chains and are thus called glycoproteins (gp). The knob-like structure is gp 120; the one which sits on the membrane is called the transmembrane glycoprotein identified as gp 41 on the basis of the molecular weights. The main precursor envelope protein is gp 160. Envelope proteins play important role in the initial attachment to the host cell and in other early events. Therefore, most of the vaccines developed against HIV had focused on them. There are, in addition, several regulatory proteins which are produced by the regulatory genes of HIV. Some of these help to enhance HIV production while others regulate it in a negative manner (App. 1). Tests for Laboratory Diagnosis We first go to family physicians or general practitioners (GPs) with complaints of illness. They diagnose the nature of the illness making use of their knowledge and experience. This is called clinical diagnosis on which depends what medicines are prescribed, in what form, etc. Sometimes, doctors resort to laboratory diagnosis in order to determine the nature of illness, especially to differentiate it from other similar illnesses. Laboratory diagnosis is particularly important in detecting diseases with serious health implications or those with long latent period. HIV/AIDS is indeed one such disease and hence the need for laboratory diagnosis. Specific Tests for HIV The one laboratory test to find out if a person suffers

THE VIRUS AND THE TESTS

33

from AIDS is to determine whether the number of a particular type of a cell (CD4 T-helper cell) in the blood falls below the count of 200 cubic mm (Ch. 5). This quantitative test, however, is extremely expensive. In Table 7 are listed specific diagnostic tests for HIV which are available for routine or research use. In general, these tests can be divided in two categories: indirect or serological tests and, the direct or virological tests. When blood is taken out of the body, it has a tendency to clot, i.e. to get coagulated; it leaves behind the watery portion which is called serum. Tests which are carried out on the serum (plural sera) are generally called serological tests. The resulting response of the host (seroresponse) could be termed either to be seropositive or seronegative. Table 7 Diagnostic Tests available for Routine or Research Use Indirect/Serological Methods — Detection of antibodies (EIA and others) — Detection of antibodies in different viral proteins (Western blot, RIPA confirmatory tests) — Detection/measurement of neutralizing antibodies Direct/Virological Methods — Detection of viral antigens (ELISA for p24 core antigen) — Detection of viral RNA and proviral DNA [many tests including polymerase chain reaction (PCR) among them] — Virus cultures (isolation of the causative agent from blood and other tissues/organs)

Serological Markers Various viral proteins described above act as antigens, meaning as foreign to the immune system. Therefore, the host's immune mechanism is activated to produce antibodies to fight these foreign antigens (further details in Ch. 5). Antigens and antibodies circulate in the blood; after

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separating the serum from the cellular portion of the blood, serological tests are carried out to detect their presence. Serological markers according to the time of their appearance are shown in Fig. 12. Within two to four weeks after exposure to HIV, viral particles and/or the major core antigen (p24) could be detected in the blood. During this phase, antibodies are not detectable. This initial phase of HIV infection without detectable antibodies, but with the virus (antigen) transiently present in the blood, is known as the window period. Estimates on the length of time between exposure and seroconversion (from seronegative to seropositive) varies widely; the range is estimated between six weeks to*six months (average, around 45 days).

Fig. 12 : Serological markers in HIV carriers developing AIDS.

An important point should be emphasized in relation to anti-HIV antibodies. In many viral diseases (e.g. poliomyelitis, mumps), the presence of antibodies means immunity or protection against that disease. In contrast, in HIV disease, the detection of specific antibodies (whatever the test method) is taken as the evidence for the presence of the virus of AIDS. Thus, persons with HIV antibodies are not considered immune, but in contrast, as

THE VIRUS AND THE TESTS

35

carriers of HIV. They are able to transmit the virus to others sexually or through their blood or, in the case of pregnant women, to their infants. Antibody tests are generally identified as 'indirect methods' because they detect a product of an immune reaction to the causative agent. Tests to isolate (obtain) and/or detect the causative agent or its products (antigens) are included among the 'direct' methods. Several indirect or antibody tests have been developed and still more are continuously coming out in the market. The first antibody test, called enzyme linked immunosorbant assay (ELISA or EIA), was commercially available in industrialized countries in 1985. These have been employed since then in routine diagnosis, particularly for screening of blood donors. The assay employs an enzyme conjugate which gives a colour signal resulting from the reaction

HIV DIAGNOSTIC TESTS UNLIKE MOST OTHER VIRUSES, IN THE CASE OF HIV

• Presence of antibodies does not mean that the individual is immune. • Antibodies mean that the VIRUS* is likely to be present. Therefore, tests for antibodies are routinely used for diagnosis. The most commonly used is ELISA — ENZYME LINKED • IMMUNOSORBANT ASSAY.

IT IS PERFORMED IN SEVERAL CENTRES DESIGNATED BY THE INDIAN COUNCIL OF MEDICAL RESEARCH (ICMR) AND THE STATE HEALTH DIRECTORATE APPROXIMATE COST IS Rs 40 PER TEST. •Detection of virus/antisen and/or cultivation of HIV in specialised cell Cultures is used for research rather than routine diagnosis.

Fig- 13 : HIV diagnostic tests.

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CHALLENGE OF AIDS

between specifically bound enzyme and a substrate. A photograph of the ELISA plate with some information is reproduced in Fig. 13. Over the last few years, EIA have been developed which use components/reagents vastly improved in quality from those used in the 'first generation' tests. Since ELISA is the most commonly used test in blood banking services, most commercial kits tend to be so sensitive as to pick up even some 'false positive' samples. Interpretation could be difficult, and in several instances, confirmation is needed. Confirmatory Tests Western or (immuno) blot test is the most widely applicable confirmatory test. The name Western does not arise from the geographic (industralised) region. It came about from the scientists' ingenuity, both in developing this new technology and in naming the tests. A man called Southern devised a method to identify DNA fragments; the test was referred to as Southern blotting. Later, some other scientists developed a similar technique but for RNA. Although their names were different, the technique was known as Northern blotting. As it generally happens, soon thereafter an immunoblot to identify various proteins (polypeptides) was described. This came to be known as Western blot. HIV/AIDS has imparted to this last test an extraordinary importance. In Fig. 14, some information on the test is presented. In addition to this, there are other confirmatory tests, but they are much less known. These also require some specialized reagents/equipment and are therefore not very widely accepted. One of these is called immunofluorescence assay (IFA). It uses a specialized dye which fluoresces under a special microscope and can thus point out where viral antigens or antibodies are located. Another good confirmatory test, called radio-immuno (precipitation) assay (RIA or RIPA), is also available. However, it requires

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37

WESTERN BLOT IS A CONFIRMATORY TEST FOR ANTIBODIES DETERMINING HIV PROTEINS

THIS TEST IS PERFORMED ONLY IN 5-6 REFERRAL CENTRES IN INDIA. COST IS APPROXIMATELY Rs 700-800 PER TEST SAMPLE

Fig. 14 : HIV diagnostic confirmatory test.

very specialized facilities to use radioisotopes, which are not commonly available. In countries where laboratories can afford to use the Western blot, it is found to be the confirmatory test of choice. In fact, it has often been called the 'gold standard' and frequently employed for comparative evaluation of

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various newly developed serological tests. Interpretation of Western blot is, however, still debatable especially regarding how many bands and for which particular structural antigens should be considered as positive. Other Simpler and/or Rapid Indirect Tests Diagnostic tests, which can give results in minutes instead of hours, have also been developed and evaluated. Some of these do not even require instrumentation and are therefore very useful in areas where instruments (such as ELISA readers) are not available, or if available, cannot be maintained. Several of the rapid tests have a potential for being used in emergency situations; for example, screening blood for immediate transfusion. One drawback is the high cost of such kits. Tests have been developed based on the principle of antigen-antibody agglutination; one such, namely SERODIA (from Fugirebio Inc., Japan), has been found to be very useful. It takes about a few hours (three to four hours) but requires no1 instrumentation. It is very sensitive and therefore requires an additional test for confirmation. Some commercial houses have produced 'Use Yourself' type of simple kits to be directly used by the end users, as in the case of pregnancy tests. There is, however, a reluctance in the UK and USA to allow this test because it is feared that positive results without any support from doctors and counsellors may lead to undesirable consequences. Among indirect testing is also included a special test applied mainly for research and in vaccine studies. This measures neutralizing (N) antibody in circulation. N antibodies combine with the virus and thus neutralize it to prevent its replication. As mentioned earlier, in HIV infection even N antibodies are not always protective. This is because the AIDS virus is found to change rapidly even within the same person, thus avoiding neutralization.

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By the time antibodies appear for this 'changed' virus, the devious HIV might have modified once again, thus evading neutralization. Quality Control and Interpretation of Serological Tests In view of the medical and particularly social significance of a seropositive result, extreme caution is required in the performance of the various serological tests and their interpretations. The aim should be to obtain accurate results so that a correct interpretation can be made. A 'false positive' result is potentially tragic and should be preventable before conveying to the concerned person. On the other hand, if 'false negative', the infected person may continue to infect others through high risk behaviour. Quality control at every stage of testing should be introduced; similarly, proficiency of those carrying out the test should be checked periodically. Interpretation of ELISA is also very important. Since most kits are made so as not to miss any real positive, these are very sensitive in their reactions. A serum sample which gives a positive indication at first testing is called ELISA reactive. It should be repeated, preferably using a different kit. Only repeatedly reactive sera are considered seropositive. Not only medical and social but even ethical, legal and economical issues are implicated in testing; these aspects including pre-test and post-test counselling are discussed later (Ch. 8). Direct Tests Diagnostic tests dealing with isolation of the virus either from blood or other tissues and organs or detecting the presence of the virus or its products (proteins/antigens) are called direct tests.

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A m o n g antigen detection, p24, the major core antigen appears first. Antigen detection kits are also based on the same principle as EIA, but they are very expensive. Furthermore, the test is not routinely applicable as the antigen is present only in the very early phase after exposure. As shown in the Fig. 12, HIV antigen again appears in the circulation, coincident with the drop in antibodies to this antigen. This stage coincides with the progression of HIV infection to AIDS. Therefore, p24 antigen testing becomes a useful prognostic 4 marker. This phenomenon, which is regularly seen in patients in Pattern I countries is, however, not significant among patients in (Pattern II) African countries. Its significance yet remains to be determined in India. Isolation of the virus from HIV-infected and AIDS patients is a useful research tool, especially in the development of vaccines. It helps in characterizing and comparing HIV strains obtained from different situations and in different regions. The virus(es) from Africa are genetically different from those in USA. On the other hand, isolates from the IV drug addicts are reported to be different from the virus strains isolated from HIV/AIDS patients who became infected through the sexual route. The latter differences have been noted among the strains isolated from the same region in Thailand. Detection of viral RNA and complementary DNA has mainly been employed for research purposes. A more recently developed test, called polymerase chain reaction (PCR), has the greatest potential not only in research but also for routine use in some special conditions. The test can determine RNA—the genetic material of HIV—and also, the proviral DNA (App. 1). The extracted material from blood or other sources is amplified tremendously so as to yield sufficient amounts which are then identified by using certain 'primers'. 4

A forecast of the course of the disease.

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41

Situation in India In India, ELISA is the most widely used test with Western blot as a confirmatory test. During the early phase of the epidemic, this strategy worked out satisfactorily. However, with the increase in the number of seropositives, the expensive confirmatory test now needs to be performed on a much larger number. Therefore, alternative strategies have been developed on the general principles recommended by the WHO, also keeping in mind our culture and socio-economic conditions. There is an urgent need to develop strategies for the diagnosis of various AIDS associated infections, including opportunistic infections. At present, there are more centres/laboratories to carry out serodiagnosis of HIV/ AIDS as compared to those engaged in diagnosis of viral diseases such as herpes viruses, or for sexually transmitted and parasitic diseases. This situation should be rectified because many of these diseases are not only preventable but curable and, therefore, should be identified and tackled in time.

Appendix 1 Fig. I a and b : depict the life-cycle of HIV within a human cell. The genome of the viral RNA transcribes DNA with the help of the reverse transcriptase. This DNA gets circularized and gets integrated into the host cell DNA in a 'proviral form'. Some of the DNA can also remain in unintegrated form. Later, the proviral DNA makes the required proteins using the cellular machinery of the host (under the viral demands) to form viral particles. Finally, the virus 'buds' through the host cell membrane—picking some cellular component in the process—and emerges as mature HIV which can infect other cells.

Fig. I a : depicts the life-cycle of HIV within a human cell.

APPENDIX 1

43

g- I b : depicts the life-cycle of HIV within a human cell. [Reproduced from Zenda Rosenberg and Anthony Fauci, New Scientist, 125 (1703) p. 51, Feb. 1992],

Fl

4

NATURAL HISTORY OF AIDS The Range of HIV Disease The natural history of an infectious disease concerns with how an organism survives in the infected host, produces the clinical symptomatology and the final outcome. Infection with HIV produces a very varied and wide-ranging clinical picture (spectrum), having at one end a mild 'flu-like' illness and, on the other, what was called as full-blown AIDS. Following the exposure to the virus, events that occur in infected hosts are mild, mostly silent. Stages of progression of HIV infection to full-blown AIDS are presented in Fig. 15.

Fig. 15 : Stages of HIV-related diseases.

Acute HIV Infection : Approximately three to six weeks after exposure to HIV, several individuals develop an acute, 'flu-like' illness. This acute phase may be accompanied with fever, sore throat, joint and muscle pains,

NATURAL HISTORY OF AIDS

45

d other non-specific symptoms. This illness is on the whole so mild that it passes off as unremarkable at the time and certainly not remembered much later. At the end of this phase, the majority of the infected persons develop anti-HIV antibodies which are detectable in the blood. Therefore, this acute phase is also called seroconversion illness. This early-phase mild type of illness (which resembles several other acute viral illnesses) is the main reason why some scientists—especially an American retrovirologist, Prof. Peter Duesberg—have initiated a controversy concerning HIV not being responsible at.all for AIDS. However, the peculiar nature of HIV and, in fact, all retroviruses (reverse transcription), combined with various epidemiological features have convinced most scientists and doctors that HIV is indeed the major culprit although many other (infectious and non-infectious) factors may be aiding and abetting it in provoking the progression to the final stage, namely the full-blown AIDS. These are described in the next chapter. Asymptomatic Stage : Following the acute phase, whether recognized or not, infected persons enter an asymptomatic stage of HIV disease; they remain healthy, with no signs and symptoms of any illness. As mentioned earlier, they are considered to be potential virus carriers, meaning thereby that they are able to infect others via their blood or sexual fluids. Persistent Generalized Lymphadenopathy (PGL) : Some of the HIV-infected persons pass through this stage clearly while others do not. During the stage, infected persons exhibit obvious enlargement (swelling) of glands (lymph nodes) present in the neck and armpits; except for this, the patients may look and feel normal. The swelling of he glands is a defencive response of the infected individuals brought about by their immune mechanisms. Since

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this type of response could also occur in other conditions, it is difficult to diagnose AIDS at this stage also. AIDS Related Complex (ARC) : Infected people during this stage begin to show constitutional (related to the body or mind) signs and symptoms. ARC covers a wide range of the disease. Actually, this stage was considered significant for diagnosis of AIDS mainly at the time when specific laboratory diagnosis was not available. ARC is diagnosed in a person who has a continuous (for three months or longer) low grade fever and who has lost more than ten per cent of the body weight or has persistent diarrhoea; other symptoms could be extreme loss of energy, night sweats, etc. In the developing countries with poor nutrition and a heavy load of other infections, all these signs and symptoms could occur due to some other cause(es). Therefore, diagnosis of HIV/AIDS would still be difficult. Generally, however, a physician will request a specific laboratory diagnosis to be made if there is a suspicion that the patient might have encountered a high risk situation for AIDS. Acquired Immune Deficiency Syndrome (AIDS) : This is the last stage of the HIV disease spectrum. At this stage the infected patients develop one or more disease(s), mostly arising out of opportunistic infections or cancers. Some infectious agents—parasitic, bacterial, viral and fungal— remain silent, unexpressed in the body. They grab the opportunity to inanifest themselves and cause illness when the body's resistance (immune system function) is depressed. They are called opportunistic infections,/diseases. This also applies to some malignant cells kept under control by a strict immune surveillance system. Once the system weakens or fails, the cells take the opportunity and grow as opportunistic cancers. Most of the opportunistic diseases can be overcome

NATURAL HISTORY OF AIDS

47

w j t h intact immune mechanism; however, in tients with AIDS, they become life-threatening because J^e body's defence has markedly declined due to the , „i e tion of a particular type of CD4 positive T-helper cell (a type of lymphocyte) which plays a key role especially in c e l l - m e d i a t e d immunity (Fig. 17 on p. 52). s o n s

It is now established that the HIV disease is a chronic illness; its duration (survival time) depends on many influencing factors including nutritional, other infectious agents, and, of course, on prompt recognition and treatment of opportunistic infections. The average (median) time elapsing from the initial infection to the development of disease is currently estimated to be about ten years. Disease Manifestations Diseases accepted as indicating immune deficiency related to HIV are shown in Fig. 16. Frequently, the first presenting illness, that is the disease which makes patients seek help from doctors, are those of skin and oral cavity. Skin diseases often start with excessive itching and progressively become so severe that they "drive patients almost crazy", as commented by a specialist. Among the various skin manifestations, Kaposi's sarcoma (an opportunistic cancer) is the best known. It is, however, suspected to be caused by yet another sexually transmitted (viral) agent. Among the organs, lung is one of the most affected. Breathing difficulties due to pneumonia, phlegm and blood in the sputum and chest pains are common features. Infection of the gut leading to gastrointestinal symptoms is particularly common in poor environmental conditions. The nervous system is also affected and has a wide range, from dementia (deterioration in mental condition) to AIDS encephalopathy (inflammation of the brain), to abscesses and cancers of the brain. Geographical differences have been noted for several

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VIRAL FUNGAL

AIDS-DEFINING INFECTION

BACTERIAL PARASITIC

TUBERCULOSIS BACTERIAL ORAL HAIRY LEUKOPLAKIA VIRAL SEVERE ATHLETE S FOOT FUNGAL THRUSH (MOUTH & TONGUE) FUNGAL SHINGLES (SKIN) VIRAL BACTERIAL SKIN INFECTION

CD4+ T LYMPHOCYTES PER CUBIC MM

Fig. 16 : Diseases accepted as showing immune deficiency related to HIV.

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49

AIDS-associated illnesses. For instance, the parasite Pneumocystis carinii pneumonia is most frequently seen in patients in the industrialized Western world, while in Africa and other countries of Patterns II and III, bacterial pneumonias are more common. Similarly, tuberculosis associated with HIV is much more common in the countries of Patterns II and III (including India), whereas other member(s) of the same group of bacteria—mycobacteria atypical variety—is most frequent in the countries of Pattern I. A recent report from Rwanda in Africa showed HIV to be highly prevalent among patients visiting skin disease clinics. Diseases had a particularly poor response to treatment. Kaposi's sarcoma (KS)—a cancer of the skin and some internal organs—is most common among male homosexuals, especially in the Pattern I countries. In India, KS has so far been rare, whether associated with AIDS or not. During the first year after recognition of AIDS, most clinical definitions had disregarded disease manifestations in women. Perhaps, it was because men with HIV outnumbered women in the developed countries where most of the definitive studies were made. Now that women have also been affected in large numbers, many investigations have been conducted on women, especially to include gynaecological findings. Several recent studies have shown clear gender differences in the clinical status and organ involvement. For example, more men (53 per cent) suffered from skin diseases than women (32 per cent). In contrast, more wornen (43 per cent) had genito-urinary conditions as compared to men (14 per cent). Scientists feel that many such gender and geographical differences are more likely to reflect differences in the mode of exposure and dosage of the virus, environmental conditions and, of course, the general well-being and immune status of the infected patients.

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Paediatric AIDS : A positive diagnosis of AIDS is particularly difficult in children although many similarities exist between adult and paediatric clinical manifestations. HIVinfected children develop numerous bacterial, parasitic and fungal infections. In countries of Africa and Asia, the struggling economic plight combined with inadequate food and numerous infections further enhance the deadly effect of HIV. AIDS in children can be divided into two patterns of disease progression. Infants who show illness before the first year rapidly progress to death, usually within seven to ten months from the diagnosis of AIDS. Children who show symptoms only after two years or so, develop a disease course more like that seen in adults. In addition to receiving HIV from their infected mothers, children can also get HIV through infected blood or unsterilized/contaminated needles and syringes. Clinical Course and Manifestations with HIV-1 and HIV-2 The clinical picture of patients infected with HIV-1 is similar, though not identical, to that presented by those infected with HIV-2. Many studies record slower and less aggressive course of disease with HIV-2 as compared to HIV-1. According to a study made over a period of six years, persons infected with HIV-2 are ten to 12 times less likely to develop AIDS than persons infected with HIV-1. More recently, it has been shown that HIV-2 is not only less pathogenic than HIV-1, it also spreads much slowly than HIV-1.

61

THE ENIGMA OF AIDS : HIV VERSUS T H E IMMUNE SYSTEM Every healthy living being has an efficient mechanism to protect against a disease which facilitates to develop 'immunity' against that disease. This is achieved with the help Qf an efficient 'immune response' which depends on a coordinated attack of a variety of cell types. In general, it is called the defence mechanism, whereby an army of specialized cells forge a battle against any invader. 'Active immunity' is acquired by an 'infected' individual through his/ her body's own effort (e.g. in response to natural infection or vaccine). In contrast, 'passive immunity' is transferred to an individual in the form of ready-made antibodies collected from persons already immune to that disease. Components of the Immune System Various cellular components implicated in the human immune system are shown in Fig. 17. Bacteria, viruses and various such 'unwelcome' micro-organisms invade the body after overcoming the 'first guards' of the body. These are the skin and mucosal surfaces (mucous membrane is the lining of different cavities of the body open to the exterior, e.g. oral cavity or the mouth). Once the germs have sneaked in, they roam around and attack (infect) their favourite target system, namely, respiratory, gastrointestinal, etc. Macrophages : Within the body, the first encounter of the

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Fig. 17 : Major cellular components of the immune system.

foreign invader is with macrophages and their precursors called monocytes. Macrophages are highly mobile cells which may be termed 'scavengers' because they clean up the system by engulfing the invaders in an attempt to get rid of them. This process of engulfing the particulate

t h e e n i g m a o f aids : hiv v e r s u s t h e immune system

53

invaders is called phagocytosis. Macrophages are very mobile, a property which enables them to reach virtually every corner (tissue) of the body of the infected individual. Lymphocytes : These are white blood cells which play a very important part in the immune system. There are two major groups : the B cells (considered to have originated from the bone marrow), and the T cells which originate from the thymus gland. B Cells : These are lymphocytes which are responsible for the 'humoral' arm of immunity (described below). On encountering antigens, some of the B cells begin to replicate their own kind and then secrete antibodies which circulate in the bloodstream. Other type of B cells are called 'memory' cells. They are so-called because they have been 'primed' to retain the memory of an antigen. The cells remain silent and get''activated' only when they again encounter the particular antigen; they then produce an accelerated (secondary) antibody response. T Cells : During foetal life, 'stem cells'—the original cell type—migrate to the thymus gland. There they pass through certain phases and ultimately emerge as 'mature T cells'. They enter the circulation (blood) and concentrate in the spleen, mucosa and lymph nodes (glands), where they are most likely to encounter foreign invaders (antigens). The T cells constitute the cell-mediated immunity (CMI). There are two major subgroups among the T cells. Those which carry CD4 cell surface protein are called CD4 cells. They are known as helper/inducer T cells (Fig. 17). The second type are those bearing CD8 marker and are termed cytotoxic/suppressor T cells. As these names signify, they perform more than one function. However, these functional distinctions cannot be made on a routine basis but require specialized techniques.

103 . c h a l l e n g e OF aids

Antigen Recognition Both B and T cells are armed with the mechanism to recognize and respond to foreign invaders. There are, however, differences in the way they go about it. The antigen receptor for B cell is the antibody molecule which is anchored in its membrane. It recognizes antigen in a direct way. The T cell antigen receptor is quite distinct from the antibody molecule. It does not recognize the antigen directly. It can bind to a foreign antigen only if the antigen is appropriately processed and presented by cells which are called antigen presenting cells (APC). Yet another complex feature is that the function of T cells is dependent on a specific manner of antigen presentation. In general, the CD4 cells recognize antigens presented in association with the class II histocompatibility antigen (HLA), while the CD8 cells depend on antigen presentation in association with the HLA class I. The HLA antigens are hereditary components of these cells. Antigen Presenting Cells (APC) Cells of monocyte/macrophage lineage, which act as scavengers through phagocytosis, also act as APC. Another cell of the same lineage, called dendritic cell (Fig. 17), resides in the skin, mucosal tissues, lymph nodes and the spleen. The fact that antigens are encountered first and also most (frequently) in these areas, has imparted a very important role as APC to the dendritic cells. B cells also act as APC, particularly efficiently when activated. Other Components In Fig. 17 are also shown NK cells which are lymphocytes known as natural killer cells. As the name suggests, they are potent killers, destroying infected as well as cancerous cells. In contrast to the CD8 positive cytotoxic T lymphocytes (CTL), NK cell function is not governed by

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the APCs or HLA restriction. Thus, together with phagocytic cells (macrophages), the NK cells constitute a very important 'non-specific' arm of the immune system. On the other side are cytokines which are soluble proteins released by various cells. These act as chemical messengers transmitting signals to their particular targets. The two important cytokines produced by the CD4 lymphocytes are interleukin-2 (IL-2) and IL-4. The former is required for the growth of T cells and the latter, both for T and B cells. Cytokines not only perform a variety of functions, but also have an intricate regulatory network of interactions. As depicted in Fig. 17, CD4 T cell is the single most important component of the immune system. In fact, it influences functional capabilities of all other cells of the immune system. With such a complex system, it should be obvious that a proper balance of all the components of the defence mechanism, including the soluble messengers (cytokines), is essential. Maintenance of a coordinated and effective immune response is thus a crucial element in any individual's well-being. That this balance is totally disrupted in AIDS is a tragedy. HIV appears to be the major villain though it is aided and abetted in the task by other agents which are called co-factors. Immune System under Attack of HIV The crucial importance of the CD4 cell in mounting an effective immune response has been described above. This, however, is the very cell that HIV has chosen as its major target. The entire immune system—not only the infected CD4 cells—ultimately come under the attack of HIV. No doubt, during the very early phase of HIV infection, an effective immune response is mounted against HIV since CD4 and various other cells are not much affected. In most acute viral infections, such a response is enough to eliminate the virus from the system. In fact, thereafter, in

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many viral infections, 'memory' cells, which are present when they encounter the antigen again, produce antibodies (secondary) very fast, get rid of the virus and thus maintain the immune status. If this happens with many viruses, why does HIV behave differently? It appears that HIV and other chronic virus diseases establish a very close relationship with certain cells. They hide into these cells so that antibodies circulating in the blood are unable to reach and 'neutralize' the viral effect; HIV can thus establish latency. 5 However, the virus waits for an opportunity to get out and infect other cells. This happens when the virus-carrying cell is 'activated' and starts producing cellular products that the virus can utilize for its own replication. Significantly, the HIV-infected cells get 'activated' when they need to fight other infectious agent(s) which enter the area. In other words, these infections help the virus of AIDS to replicate by using the machinery of the host's activated cells. The three important immune responses of humans to HIV are shown in Fig. 18. As soon as the virus undergoes maturation and 'buds out' of the cell membrane (App. 1), the specific antibodies in the blood attach to the (virus) particles in an effort to eliminate them (neutralizing antibodies). This leads to a see-saw battle between the virus and the antibodies. In excess of antibodies, the virus will be ineffective. In addition to the antibodies, i.e. humoral immune mechanism, the cell-mediated immune arm is very important. HIV can spread from cell to cell without getting into the bloodstream where antibodies can neutralize it. Therefore, CMI has to get into action by alerting the concerned mechanism. As explained in Fig. 18, killing of infected cells takes place by two specific immune mechanisms : namely, cytotoxic T lymphocyte (CTL) killing by CD8-receptor positive T lymphocytes and 5

Hidden, inactive for the time being.

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Antibodies A. Neutralising Antibodies: These bind to HIV and form antigen-antibody complexes— which are destroyed by other immune components. Antigen/antibody complexes

B. Antibody-Dependent Cellular Cytotoxicity (ADCC): Natural killer (NK) cells recognise and destroy antibody-coated HIV-infected cells.

C. Cytotoxic T Lymphocyte Killing: These CD8 receptor-bearing cells are very important in immune system. They recognise and destroy HIV-infected c6lls if antigen is displayed appropriately.

Fig. 18 : Triple defence—three host-defence mechanisms have been demonstrated to act specifically against HIV.

antibody dependent cellular cytotoxicity (ADCC) by the NK cells. The virus, devious as it is, has yet another mechanism for its counter-attack. It changes its antigen— especially the outside envelope antigen—so that the modified one can escape detection by the already formed antibodies. By the time antibodies to the 'changed' antigen

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appear in blood, HIV might have changed once again, thus making its escape from the attack by the humoral immune system. In these circumstances, the role of CMI is crucial against HIV. In addition to the CD4 cells, HIV can also remain hidden in macrophages and dendritic cells. Thus it affects all the cells which are most important, especially in cellmediated immunity. Autoantibodies This then is the intricate attack of the virus of AIDS which, from the beginning, has been posing a challenge to scientists. At first, a simplistic view was taken to explain the virus armament. It was thought that immunity is affected because of the direct effect of HIV on the crucial CD4 cell. This was also the explanation given for the marked depletion of this cell which coincided with the progression of HIV to AIDS. That things were not as simple as believed at first, became obvious when more studies were undertaken. It appeared that there were qualitative changes during the early phase which went unnoticed. Later studies led some scientists to hypothesize that AIDS pathogenesis was not due to a lack of immune response but probably resulted from too much of a (certain kind of) response. It was shown that B cells of the infected individuals produced antibodies not only to the 'non-self' viral proteins but, also to the host's own cellular antigens. Such antibodies to self antigens are called autoantibodies. Antibodies to lymphocytes and even against histocompatibility antigens have been found in AIDS patients. This has been attributed to the similarity in a fragment of HIV envelope antigens (gp 120 and gp 41) with a part of the human HLA. It has been realized that much greater complexity is involved in the immune response to HIV. Not only the disturbance in CD4 functions, but in the functions of antigen presenting cells (macrophages and

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dendritic cells) were noted. Although the virus does not seem to damage these cells directly, the functional ability of these, cells appears to be impaired. Functional Loss of CD8 Cytotoxic Lymphocytes (CTL) Another feature that came to light concerned the CD8 cells called cytotoxic/supressor cells. Using specialized markers, a defect has been found specifically in their killing function. Although there is not much of a quantitative change, i.e. the absolute number of CD8 cells may not be affected, a qualitative change is noted. These CD8 cells lose their capacity to kill the virus-infected cells; instead, the majority of these cells act as 'suppressor' cells, further diminishing the immune response. Marked reduction is also noted in the number of NK cells which perform a very important function of killing cells which are cancerous or are infected with HIV. Cytokines, Growth Factors and Cancers Investigations on the soluble chemical messengers (cytokines) also revealed changes, which could be pathogenic, i.e. disease producing. It has been recently realized that HIV-associated cancers like Kaposi's sarcoma was probably due to chronic activation of the system, and the release of a cytokine that could act as a growth factor. Thus, the cells would keep on growing in an unregulated manner leading to cancers. Similarly, cancers of B cells, called B cell lymphomas have also been attributed to a cytokine that induces an oncogene which is a cancer producing gene. NK cells, which, in normal circumstances kill cancer cells are also depleted and functionally defunct. In brief, perhaps in an oversimplified way, an attempt is made here to explain the extremely complex pathogenetic mechanism(s) of the virus of AIDS.

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Does HIV cause AIDS? Earlier (Ch. 4) a reference was made to Prof. Peter Duesberg, who started a controversy that HIV is not the cause of AIDS. Because of this attitude, he had at first been ignored or ridiculed by several virologists working with HIV. Later, however, it appeared that some other scientists had joined him in this campaign. After several press releases and TV interviews, it was decided to hold an 'Alternative AIDS Conference' in Amsterdam to precede the International Conference on AIDS being held at Amsterdam from 19 July, 1992. Interestingly enough, the press in India also gave more publicity to this event than that generally given to international conferences on AIDS being held every year. Therefore, it is important to briefly describe the outcome of this 'Alternative AIDS Conference' held on 14 May, 1992. According to a report by John Maddox, editor of the weekly Nature (London), it seems that "Duesberg's arguments gained no new ground at the Conference". In fact, Maddox sums it all in his title: 'Rage and Confusion Hide Role of HIV'. However, the controversy continues; pro-Duesberg letters that doubt whether HIV causes AIDS are being published mainly in The Times of London. In contrast Nature has been publishing letters refuting the arguments, and in support of HIV as the causative agent of AIDS. HIV may not be the sole direct cause of AIDS; could it be considered as an opportunistic infection? As stated in the introduction, acquired immunodeficiency-like syndrome has not been uncommon in tropical, economically developing countries of the world. The syndrome might have been attributed to 'old' parasitic diseases, complicated by viral/bacterial/fungal infections, and further compounded by nutritional deficiencies. Since definitive studies on sub-populations of CD4 or CD8 cells were not carried out (even now, these studies are not carried out

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routinely), it is not possible to comment on the nature of immune deficiency. Some of the recent developments lead to an interesting concept. Could it be that some different, retroviral-like agent not yet identified, could have been responsible for this old-fashioned acquired immunodeficiency? At the July, 1992, International Conference on AIDS in Amsterdam, several reports were presented of patients with AIDS but without evidence of HIV infection. One particular report from Dr Sudhir Gupta from USA created quite a wave. This was a report of an HIV negative 66-year old female patient 6 of AIDS, from whom a 'new' type of retrovirus, called by the authors human intracisternal retrovirus, was identified. The same was also recognized in the patient's 38-year old daughter, who had no manifestations of the disease. This is personally important, because, at the 1988 International Conference on AIDS, this author, together with co-workers from the National Institute of Virology (NIV) at Pune, had reported (Abst. No. 1132) identification of intracisternal A particles of a retrovirus in an asymptomatic pregnant prostitute from Tamil Nadu. The prostitute, who was among the first recognized cluster of HIV seropositives (Ch. 2), had become pregnant later. At the time of her delivery, however, she had become HIV seronegative. Because of the difficulty of growing this agent, we have not been able to get it genetically characterized, but there is evidence that it produces p24 antigen. These particles, however, have not been incriminated in any human disease. The condition of 'AIDS minus HIV' was termed idiopathic CD4 + T lymphocytopoenia (ICL). This means loss of CD4 + T lymphocytes due to unknown cause(s). Several meetings were held including the one by the World Health Organization (WHO). Finally, it was decided that no worldwide surveillance was needed in the absence of Deficiencies and impairment in immune mechanisms in the elderly are not uncommon.

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any epidemic spread and also, the lack of evidence for transmission of any infectious agent. Suspected Co-factors Scientists now believe that although HIV is necessary to cause AIDS, without co-factors it may not be sufficient by itself. As has been explained earlier, HIV remains in a latent state for long periods in certain cells. These are the cells likely to be activated by infectious agents or under other stressful conditions. Among the various cofactors, sexually transmitted diseases (STDs) are known to facilitate transmission and spread of HIV among people at risk. A very long list of agents like viruses, bacteria, parasites or mycoplasma (and/or their products) have all been associated some time or other with HIV as a cofactor responsible for AIDS. At present, each AIDS expert or virologist seems to offer his own 'pet' as a co-factor. For instance, Montagnier banks on mycoplasma (a germ which is neither quite like a bacterium nor like a virus), while Gallo, the virologist from USA, opts for viruses of herpes group and also the human retroviruses. With more work being done in newer areas where cases of AIDS have increased, it seems that we need not look for the

Fig. 19 : The last straw that broke the camel's back.

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one and the same co-factor in all cases of AIDS. As a matter of fact, immune response factors described earlier in this chapter should also be considered important in the pathogenesis (immunopathology) of AIDS. One such important one is the genetic marker, i.e. certain human HLA type(s) which have similarity to some important antigens of the virus of AIDS. Several proteins produced by HIV genes have been shown to have a close relationship with several important cellular components. It is possible that any one or more of these could trigger progression to AIDS. In the final analysis, we may conclude that it is the last straw that breaks the camel's back (Fig. 19). But, does it have to be the same straw in every AIDS case, everywhere and every time?

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H O W TO SURVIVE T H O U G H HIV-INFECTED Imagine a sick bed in a very poor, respectable household. A doctor is examining the patient and then tells the father/mother/son/daughter that the patient's condition is very serious. But, there is still hope for a cure if the patient is given a particular medicine in time. The relative is in trouble as there is no money to spend on such an expensive medicine. Somehow, with difficulties and some added debt, the said medicine is procured. The patient receives a few capsules and is on the way to recovery. A few days more, and the person has fully recovered. This scene, often depicted in our films, could well describe how effective an antibiotic can be. Fevers, pneumonias, many other illnesses caused by bacteria are normally curable when the right kind of antibiotic is taken appropriately. Unfortunately, there is no such magic bullet antiviral for HIV. In fact, in the majority of virus diseases, drugs are used to treat symptoms rather than specific viruses : something for headache, or vomiting and nausea ; even antibiotics to prevent 'secondary' bacterial infections. Many antivirals have been developed and several are used effectively, particularly against influenza and some herpes viruses. However, these are quite expensive and not easily available in India. Anti-HIV Drugs No other infectious disease has attracted greater attention

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of scientists and manufacturers of life-saving drugs than has AIDS. Each year, more drugs and other agents with immunity-boosting properties (immunomodulators) are developed for the first phase of testing. Many are abandoned as being no good, while a few enter a further phase of clinical trials. Some of these are carried still further in larger trials. As with bacteria, some drugs produce resistance in the virus of AIDS and therefore become ineffective. In bacterial diseases, resistance develops especially due to injudicious, improper or incomplete use of antibiotics. The first drug to pass through the US drug control and the one most commonly used in HIV/AIDS is called

Fig. 20 : AZT is not the complete cure for AIDS.

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AZT (zidovudine). It does not cure patients but helps them to live longer. However, it does produce several undesirable side-effects. After a continuous treatment, HIV can also become resistant to AZT. Therefore, despite very heavy expenditure, AZT is not the complete cure for patients with AIDS (Fig. 20). More recently, zidovudine has been shown to be effective in preventing the transmission of the virus from HIV-infected mothers to their infants. However, in the absence of similar (control) trials in the developing world and the heavy cost of medication, it is difficult to predict its impact on the spread of HIV in India. A large number of antiviral agents having different Table 8 Some Anti-HIV Compounds/Agents* Early blockers of HIVcell interaction

Sulphated polysaccharides/polymers (e.g. Dextran sulphate), CD4, especially as immunoconjugates, monoclonal antibodies: peptides

Inhibitors of reverse transcriptase

HAPT derivatives: Acyclovir, AZT, Carbovir, ddl, ddA, ddC Suramin derivatives: Foscarnet, Ribavarin, TIBO derivatives

Viral protease inhibitors (inhibits gag-pol fusion cleavage)

Synthetic peptides

Myristosylation and glycosylation inhibitors

Castanospermine, DNM (deoxynojirimycin)

Immunomodulators

Natural : interferons (especially alpha) Interleukin-2 colony stimulating factors Synthetic : several used (e.g. Pentoxifylline, MIMP)

Miscellaneous, mainly herbal

e.g. Glycerrhizin, Polyxylan, Prunellin, Trichosanthin (TAP 29)

'This list is illustrative and not meant to be exhaustive.

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properties have been developed. These are associated with a particular stage of HIV life-cycle when intervention is possible (Table 8). The use of traditional herbal medicines are encouraged by the World Health Organization (WHO) and some of the remedies provided by China have yielded encouraging results. In India, systematic studies have not been carried out either with the newly established antivirals or with our traditionally known medicines. A practical approach is to combine antivirals with immunomodulators : the former to interfere at an important stage of the HIV life-cycle, and the latter to build up the immune system of the infected individual. Among the latter, CD4 molecule in soluble form—not on cell surface—is introduced in blood circulation. Interferons— substances with some non-specific type of antiviral action—and some cytokines or their antibodies are also being tried. Drugs for Opportunistic Infections On the one side are various difficulties in finding out a miracle cure for HIV/AIDS, while on the other side of the coin are the variety of opportunistic infections which become life-threatening, each of which requires appropriate therapy and management. It seems that for a long time to come, the survival time and comfort of patients will depend greatly on therapies (cures) which are specifically directed against individual opportunistic infection. At least in some developed countries, work on identifying the important opportunistic infections (OI) and developing appropriate strategies for their treatment are being worked out. Attempts to develop newer curative agents have also been taken up. A spin-off will be availability of effective drugs against a large variety of certain fungal and parasitic infections (worms, protozoa and others).

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As described earlier (Ch. 4) the nature and types of OI vary in different regions. Tuberculosis is so far found to be the most frequently associated disease with AIDS in India as in several countries of Africa. WHO has in fact declared tuberculosis (TB) as a global public health emergency. There has been a re-emergence of TB in the USA firstly because of its association with HIV and secondly, due to the emergence of multiple drug resistance shown by the mycobacteria which cause TB. Utmost importance needs to be given to diagnose and treat TB patients with effective drugs rather than wait and attempt to treat them with far more expensive antiviral drugs. Among AIDS-associated enteric (intestinal) infections, severe diarrhoea is caused by bacterial and more particularly parasitic agents. Although these were not common in the industrialized developed countries before the advent of AIDS, a large number of case reports of such AIDS associated diseases have now been published. In contrast, although they might have been prevalent in our country, a parasitic agent like crytosporidium, attributed to causing diarrhoea in AIDS patients is being described in association with AIDS. In contrast, another parasite of the respiratory system, Pneumocystis carinii, seems to be less frequent in the developing countries as compared to the Pattern I countries. Here again, intensive search has not been made to look for this parasite in India. It is essential that we develop our own data bank of these infections by collecting information available on opportunistic infections which occur due to immunosuppression induced by doctors (Fig. 2). It is imperative that a list of these infections and strategies for their treatment and prevention are prepared in time before they overwhelm us. Management of Patients Prevention of the spread of HIV infection and proper

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management of patients with AIDS are the two most powerful tools to fight HIV /AIDS. Prof. V. Ramalingaswamy, the former Director General of the Indian Council of Medical Research (ICMR), has repeatedly stated: "To care for patients with AIDS is a duty To prevent AIDS is a responsibility." It may be emphasized that many disease conditions in AIDS can be treated, and with proper management, PWAs can live as normal a life as possible at least between their illnesses. AIDS should therefore be treated like other chronic diseases and every attempt should be made to improve the quality of life. Avoidance of other infections is a very important intervention because these are the very factors that induce an asymptomatic HIV-infected individual to progressively develop AIDS. This is because, as explained earlier (Ch. 5), HIV is harboured in a special cell (CD4 positive T cell) which plays an important part in the immune system. These are the very cells that get activated to fight infectious agents when they enter the system. The activated cells make cellular products that are appropriated by HIV for its own replication. In other words, precautions should be taken to avoid infections of all important systems. Starting with skin and oral hygiene, infections of respiratory and gastrointestinal systems should be avoided. This means no exposure to people suffering from pneumonias, TB, flu and even common colds and, of course, avoidance of contaminated water and food. Various herpes viruses, syphilis, gonorrhoea, genital ulcers and all such sexually transmitted diseases should strictly be avoided by practising safer sex as discussed in a later chapter. This is an extremely important intervention measure beneficial to the patients as repeated exposure to HIV may accelerate the dormant HIV to AIDS progression. Balanced and adequate diet is absolutely essential as it

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is increasingly being recognized by PWAs intelligent enough to appreciate the need. For instance, Late Arthur Ash, the tennis star who suffered from AIDS—-acquired through blood transfusion—stated that any time he did not feel like eating, he mentally recalled the picture of a totally emaciated AIDS patient (Fig. 1) and thus forced himself to take adequate nutrition to avoid, as long as possible, such an eventuality. Nutritional deficiencies can themselves affect the immune system; and thus, proper nutrition including the use of vitamins is very important.7 Diarrhoeas are of frequent occurrence. Effect of certain drugs could result in nausea and vomiting on the one hand and skin allergy and hypersensitivity, on the other. Diet should be modified during these periods, but adequate nutrition should again be restored once these conditions subside. Avoidance of tobacco, alcohol and other non-prescribed drugs is also essential. These substances add insult to the injury, which has already taken place in AIDS patients. Rest including bed rest during the periods of acute illness (due to other infections including opportunistic infections), and, exercise on a regular basis during the interim periods also help the patients in maintaining a proper mental and physical balance. Stress and strain including mental tension should indeed be avoided. Stress, distress and a variety of psychiatric illnesses are increasingly being associated with immunosuppression. Interdisciplinary collaboration has established psychoneuroimmunology as a new field with emphasis on the elusive mind-body connection. In other words, adoption of positive health practices and a positive approach will go a long way in arresting the progression of HIV to AIDS. 7

For further reading please see 'Dietary Guidelines in HIV Disease' by Dr T.C. Raghuram [CARC Calling 5(1) Jan. Mar., 1992],

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In conclusion, it is essential for the patients' partners, families, relatives, friends, and the community in general to provide all the necessary support to AIDS patients. It is equally important to avoid causing any undue stress through isolation and stigmatization.

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D E V E L O P M E N T OF AIDS VACCINES "Vaccines are an elegant solution to one of the perennial problems of the human race—infectious diseases. The body's own protective mechanisms are primed by specific interventions to thwart the invasion or multiplication of pathogens." —Lewis Thomas Since the days of Jenner, who used a vaccine against smallpox, vaccines have become a powerful tool in the fight against infectious diseases. In the absence of any antibiotic like penicillin—the magic bullet—control of viral diseases through vaccinations is one of the most, if not the most, effective intervention. Having conquered a large number of communicable diseases through environmental improvement, the industrialized world turned their attention to controlling others with vaccines. Environmental measures included safe sewage disposal, plenty of water including safe drinking water, reduction in overcrowding, elimination of disease vectors like flies, mosquitoes and other insects, improvement in nutritional status and overall personal hygiene. Indeed, it should be emphasized that no programme of immunization will be cost-effective if these environmental factors are ignored. Commonly Used Vaccines Smallpox vaccine used as per the global strategy developed by the World Health Organization (WHO) brought

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about a spectacular achievement, namely, global eradication of smallpox. Many childhood diseases like diphtheria, tetanus, polio, measles and mumps have been conquered through effective immunization programmes. All these vaccines have been effective because these agents affect human beings only. They also elicit an immune response which is long lasting and resembles natural infection. In contrast, some infectious agents have properties which make development of vaccines against them very difficult. When Vaccine is not Effective Certain properties that characterize infectious agents are contrary to the generation of effective vaccines. In Table 9 are given four such properties together with their respective examples. Variation in antigen has always been difficult to overcome. Influenza viruses are known to show the antigenic variation, so that every few years the world faces a pandemic due to a 'new' variant. The new variants are also incorporated along with other serotypes in the manufacture of influenza vaccine. On the other side are the common cold viruses (rhinoviruses) which have more than 90 serotypes. This is the main reason why attempts to develop effective vaccine against common Table 9 Viral Properties Contrary to the Generation of Effective Vaccines Property 1) Antigen variation (many serotypes)

2) Maintained in animal(s) in nature 3) Integrates its viral genetic material into the host cell genome 4) Infects crucial cells of the immune system of humans

Virus Influenza virus, c o m m o n cold viruses (rhinoviruses), HIV Influenza, rabies HIV(?) Hepatitis B virus, HIV HIV, other human retroviruses (HTLVs)

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cold have failed so far. HIV, the AIDS virus, is a new addition to this list. In the case of HIV, a greater complexity is involved because antigenic variation has been recorded not only in geographical regions but even in the same individual (Ch. 5). The second property is regarding extra-human source of the virus in nature; again, influenza viruses fit the bill. In nature, there are influenza viruses which infect animals (horses and pigs) and birds, particularly ducks. Given an opportunity, these viruses with different antigenic structures could combine and emerge as a 'new' serotype to cause a pandemic. On the other side is the rabies virus (hydrophobia virus) with dogs as the major host maintaining the chain of transmission. Since human to human transmission of rabies virus is rare, they may be considered only as tangential hosts. In these circumstances, rabies virus needs to be controlled in the natural host (especially dogs) by vaccines so as to reduce or eliminate the chain. In contrast, HIV spreads through a chain of transmissions within humans (Fig. 8). There is neither a need nor definite evidence regarding HIV reservoir in animals. Nevertheless, the fact that the AIDS virus itself might have originated from monkey viruses (Epilogue I) lends some support to the possibility of a potential animal (simian) reservoir. The third property, that of integration of viral genetic material into the host cell genome, has been well recognized for HIV as for the hepatitis B virus. The process of integration has been presented in Appendix 1. The virus can hide in some cells where antibodies cannot reach them (this has already been described in Ch. 5). The last and perhaps the most serious factor interfering in the development of an effective vaccine against HIV is its property of infecting the very cells which are crucial to the smooth running of the immune system. This feature combined with the fact that autoantibodies

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are found in AIDS patients have led some scientists to caution against undue enthusiasm for AIDS vaccine. At the same time, there is determination to overcome all these difficulties. Further complicating these difficulties is an additional one related to anti-HIV antibodies. There is evidence that HIV also induces antibodies that enhance rather than stop the spread of the virus within a system. 'Enhancing' antibodies instead of neutralizing antibodies have been reported in HIV-infected macrophages by several workers; but as yet, no clear information is available regarding its function within the body of infected persons. Viral Vaccine Strategies The major function of a vaccine is to induce/prime the body's own mechanism so that the immune system can put up an effective fight on encountering the same agent. This should include appropriate responses from all the components of the immune system. Most commonly used 'classical' viral vaccines had been of two types. Live virus which was attenuated enough to reduce pathogenicity8 was used effectively as a vaccine against smallpox, yellow fever and poliomyelitis. The underlying principle is not only to have sufficient antigens to provoke immune response but also have the virus multiply within the host so as to give long-lasting immunity. A major concern for using such a vaccine for HIV is the potential danger that it may induce latency and may even 'recombine' with another retrovirus resulting into a pathogenic virus. Although a few scientists are still engaged on the development of 'live' attenuated vaccines, extreme caution has to be applied to such studies. The second type is the 'killed' virus vaccine, wherein 8

Disease producing properties.

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the virus is inactivated. It means that the viral agent can act only as an antigen having lost its ability to replicate. Killed vaccine for poliomyelitis (Salk vaccine) has been used in many countries where poliomyelitis has been effectively controlled. In the early stages of development, due to incomplete inactivation, some residue of live virus remained which had serious implications. Even with the vastly improved technology available now, the possibility of such an occurrence with HIV vaccine has all the serious consequences. However, AIDS vaccines following inactivation by irradiation or some chemicals are still being developed (Table 10). Jonas Salk, the developer of killed polio vaccine, has advocated a strategy of giving killed HIV vaccine to individuals already exposed to HIV but who have not yet developed any illness. The principle behind it is that the long incubation period between infection and the development of clinical AIDS may be due to an immune response to the initial infection which persists with health and wanes with disease. If this response can be boosted, it may be possible to reduce the viral burden, prevent the development of the disease syndrome and also reduce the infectiousness of the virus. In fact, more manufacturers are attracted to develop 'therapeutic' vaccines, that is to say, for treatment of already infected persons, rather than the 'prophylactic' vaccine used for prevention of infection. A recombinant vaccine using the envelope component of HIV-1 seems to have given encouraging results as reported recently. Jonas Salk is now emphasizing that smaller doses which induce a good cell-mediated immune response is likely to be more effective than those given in larger doses to induce antibodies in greater concentration. In view of the abundant precautions needed for AIDS vaccines, most of the approaches have been directed to the use of non-replicating antigens or fragments of HIV considered important in protection. Peptides, i.e. fragments

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Table 10 Types of Candidate HIV Vaccines Vaccine

Type

Live (attenuated) virus

Killed (inactivated) virus

Synthetic peptide (subunit)

Recombinant (subunit)

Micoparticle-based (liposomes and ISCOMs)

Idiotype-based

Vaccine

Components

Although considered risky, research into the use of live, but weakened, HIV is being conducted. Such research is directed to accomplish attenuation: HIV 'deletion mutants', i.e. bits of the genetic m a t e r i a l , r e m o v e d f r o m the total genomic content of HIV are being explored. The genetic material of HIV is destroyed with chemicals (e.g. formalin) or radiation while the structure of the whole virus is left intact. Both irradiated HIV vaccines and chemically inactivated HIV vaccines are in development. Protein components (peptides), more or less identical to HIV antigens, are b i o c h e m i c a l l y s y n t h e s i z e d in the laboratory. HIV antigens are produced by inserting the c o r r e s p o n d i n g g e n e ( s ) into a convenient vector. Vector systems can be used whereby a vector (e.g. vaccinia virus, adenovirus, BCG) displays HIV antigens on its surface. Certain laboratory constructs can maximize antigen presentation. Liposomes— microspheres whose composition closely matches that of cell m e m b r a n e s can enhance the immunogenicity of the antigens they carry, e.g. ISCOMs (immune stimulating complexes). Antibodies (idiotypes) that recognize an HIV antigen, can themselves elicit the production of antibodies (antiidiotype antibodies). When introduced into h u m a n s , a n t i b o d i e s to t h e s e (Contd.)

103

.

CHALLENGE

OF

AIDS

Table 10 (Contd.) Vaccine Type

Virus-like particles (subunit)

Vaccine

Components

anti-idiotypes antibodies will recognize and bind to the anti-idiotype antibodies, but more importantly, they will bind to HIV. Pseudovirions or virus-like particles (VLPs) take advantage of the particle nature of certain self-assembling viral or yeast proteins. Hepatitis B virus particulate and the yeast protein, Ty, are two VLPs in advanced developmental stages.

carrying relevant stretches of amino acids, have been synthesized biochemically; these are non-infectious. Genetic engineering (DNA recombinant) is a sophisticated technique whereby corresponding viral genes are inserted into suitable vectors. These are biologically active carriers of antigens; they can replicate without causing any ill-effects. The 'foreign' antigenic material is expressed and exposed on the surface of the vector, thus activating the immune system of individuals receiving the 'recombinant' material. It is beyond the scope of this book to cover all the vaccine developments. For those interested, some major technical developments have been listed in Table 10. Despite difficulties, enthusiasm to take up the challenge is obvious. Designing and development of effective AIDS vaccine will not only mean one of the most significant scientific/medical achievements of the century, but will also be accompanied with tremendous monetary gains. However, possible litigations and consequences of losing astronomical amounts as compensations have also acted as deterrents in some cases. Certain recent happenings described in the next few pages have further dampened the earlier enthusiasm.

DEVELOPMENT OF AIDS VACCINES

79

The 'Downs' in the Development of AIDS Vaccine Genetic and antigenic variations in HIV-1 have created major problems in vaccine production. Most vaccines used seem to develop adequate levels of antibodies to neutralize the laboratory established strains while they fail to neutralize freshly obtained field isolates. Those advocating the use of a 'cocktail' vaccine—a mixture of several different viral strains—also feel bogged down as they encounter a number of major and minor variations. Experimental animal models are very useful in understanding the various mechanisms and in assessing the safety and the efficacy of vaccines. The life-threatening nature of AIDS compels HIV vaccine developers to use appropriate animal models before undertaking trials in humans. The chimpanzee, though not ideal, is still considered the best model for trials with HIV-1 vaccine. Chimpanzees are not only very expensive, but they are not available in large numbers; hence a search is on for other animal models. Scientists have turned their attention to monkey models using simian immunodeficiency virus. Several groups had reported very encouraging results in such models which also showed protection when the immunized macaque monkeys were challenged with the original wild virus. Because of the high cost of securing and maintaining a large number of monkeys, these workers had not kept all the required experimental controls. Recently, however, a team of scientists from UK included some of these controls and, to everyone's surprise, revealed some startling findings! The 'control' macaque who had been administered 'normal human cell component' without the virus also produced immunity. The sensational item was that two of the four 'controls' were also protected against the challenge ; this was attributed to them developing ten times as much antibody against the normal human T-cell component, even though not

103 . c h a l l e n g e

OF

AIDS

infected with the virus. This challenge which is used to prove the efficacy of a vaccine is a very important step. A vaccine is considered efficacious when all (or the majority) of the immunized animals survive, while all (or the majority) of non-immunized animals (called controls) die of the disease produced by the 'challenge' virus. If, as we had seen earlier, AIDS is indeed an autoimmune disease, the finding of anti-cell antibodies in the monkeys should not be a surprise. Confusion creeps in when one begins to think how and why the monkeys resisted the strong challenge of the virus. The other side of the coin is where developers of AIDS vaccines use the chimpanzee as a model animal, especially for HIV-1 serotype. The difficulty here is to have the right type of the 'challenge' virus (HIV-1.) in sufficiently large stocks so as to standardize the test as is done for testing other viral vaccines. The task was entrusted to a virologist. He started to make a large stock but had many difficulties. Finally, after several months of work, he tried out the stock. To his and co-workers' surprise, it was found that he had not ended up with the virus he started with. What he now had was the virus from Gallo's laboratory which he had used earlier and which had somehow contaminated his stock. Embarrassing indeed for those engaged in the development of the vaccine for AIDS. But also interesting when one traces the history of Gallo's virus to find out that it was 'reportedly contaminated' by the virus strain received by him from Montagnier in Paris. The French were feeling elated, but not for long; it was discovered that even their virus strain was not the one they had started with, but was contaminated by a human immunodeficiency virus which was obtained from a different AIDS patient. All these go to show how quickly a fast growing strain of the AIDS retrovirus can overtake a slow growing one in the laboratory and cause all kinds of confusion. This feature also sounds a warning to all those engaged in virological

DEVELOPMENT OF AIDS VACCINES

81

investigations on AIDS to take abundant precautions against such an eventuality. Yet another obstacle in AIDS vaccine development is the concern about 'enhancing' antibodies (Ch. 5). It would be counterproductive if a vaccine were to induce more of this type of antibodies in the place of neutralizing antibodies. The recent finding that at least a small number of vaccinated volunteers were found to have acquired9 HIV infection has greatly upset scientists engaged in HIV vaccine research. Until all these 'downward' developments are resolved, it is difficult to predict the availability of AIDS vaccine in the near future. Situation in India In our country, where we still have to control diseases which are easily preventable by vaccines, which are cheap and adequately available, it is difficult to envisage the control of AIDS through a specific AIDS vaccine. Perhaps, it would be more important to understand the impact of various 'opportunistic infections' on HIV and AIDS and also attempt to prevent and control some of them, especially TB. In India, medical research at the national level is generally conducted under the auspices of the Indian Council of Medical Research (ICMR). Realizing the need for India to participate in the mainstream AIDS research including vaccine trials, ICMR has set up a separate institute (NARI) at Pune (Table 3). It is expected to carry out basic epidemiological, viral and immunological investigations which would help to conduct trials in future, if and when suitable effective vaccines are available. For the present, the only vaccine which seems to be cost-effective against AIDS is IEC, viz. information, education and communication/counselling. 9

Not via vaccine but through unsafe behaviour.

92

INFORMATION, EDUCATION A N D C O M M U N I C A T I O N COUNSELLING (IEC), AND, LEGAL A N D ETHICAL ISSUES "Knowledge is the most democratic source of power." —Alvin Toffler In his recent book Power Shift, Alvin Toffler (the author of Future Shock) presents an expanded definition of knowledge. He includes data, images, informations as well as attitudes, values and other symbolic products of society— whether 'true', 'approximate' or even 'false'. He states, "All of these are used or manipulated by power-seekers, and always have been. So too are the media for conveying knowledge, the means of communication which in turn, shape the messages that flow through them." Toffler points to the fundamental differences between knowledge and other lesser forces. According to him, as he calls them 'force' (coercion) is finite. There is a limit to how much force can be employed before we destroy what we want to capture or defend. This concept of knowledge is truly applicable to prevention and control of HIV/AIDS. From what we can gather, there could be two policy responses : (1) mandatory (forced?) testing followed by isolation of HIV seropositives ; it was tried in Goa but with poor result and had to be modified ; (2) the second is the integration approach wherein testing is voluntary and follows strict confidentiality. In other words, persons who are HIV-infected are not discriminated against in any way.

iec

83

Perhaps, the first policy might have worked, if we had some premonition (a vision?) of HIV visitation, much before it actually happened. Perhaps, we might have successfully spotted the few virus carriers and isolated (quarantined) them. Perhaps, we might have given proper care without undue discomfort to them or the society. Cuba seems to have followed this with some success. The reality was that we woke up too late. By that time (1985-86), the invisible virus had already created an epidemic situation. Therefore, the isolation approach would not only be unethical but also impractical and most uneconomical. Add to it, the complication of a long, indefinite incubation period and we face an impasse. Isolation for how many and for how long? Who bears the expenses for the increasingly large number of HIV-infected people? The major hurdle would be that it would indeed be counterproductive and as expalined by Toffler, in the long run, would destroy what we wish to defend. In contrast, the second policy approach helps in empowering people of all groups and ages, especially, 13 to 30-year olds, and the marginalized 10 groups, through programmes of information, education and communication/counselling (IEC); this knowledge, as defined by Toffler, is not finite. It does not get used up but, in fact, can generate more. Attitudes and approaches to life or lifestyle differ from one generation to another. This is called the generation gap; similar gaps exist between the rich and the poor. However, the greatest gap exists between the armed and the unarmed, the ignorant and the educated. Appropriate knowledge alone can narrow this gap. Concept of IEC In the last week of January, 1988, a historic, unprecedented meeting took place in London. It was the World Summit 10

Incompletely assimilated and denied full social acceptance and participation by dominant groups in the society.

103 . c h a l l e n g e

of

AIDS

of Ministers of Health from 148 countries alongwith health experts; the first occasion when a single disease syndrome was discussed at that level. From this meeting emerged the London Declaration. One of the statements included in this declaration is most relevant to the IEC concept : "In the absence at present of a vaccine or cure for AIDS, the single most important component of national AIDS programme is information and education." More than five years have passed but the situation remains the same. Five basic elements are important in formulation of IEC programmes for prevention of HIV/AIDS : 1. Accurate information about AIDS, the difference between HIV infection and AIDS, how HIV spreads and also, how it does not. There should then be specific information targeted to identified groups as to how HIV/AIDS can be prevented. 2. Scientific information in clear, unambiguous terms (preferably in local language) on human sexuality, especially to eliminate myths and misconceptions (Epilogue II). 3. Information to enable enjoyment, at the same time, control sexual and reproductive behaviour and practices so as to prevent STDs including AIDS, in accordance with prevailing cultural and social values and ethics. 4. Sensitivity to develop a positive, sympathetic and non-judgemental attitude to HIV-infected persons and PWAs (relevant to counsellors). 5. Appreciation of individual human rights and an ability to sustain a balanced view of individual rights versus protection of the public. Target Groups and Modules for IEC In CARC Calling of Jan.-March, 1990, Dr Indira Kapoor, the then Director, Government of India, Family Welfare and Research Centre in Bombay, presented a very useful

— Doctors (including G.P.s and family . physicians. — Nurses. — Dentists. — Lab. technicians. — Paramedical workers. — Traditional healers. — Traditional dais and midwives.

1

Type of groups (professional groups/keytrainers: medical, paramedical and non-medical)

The main objectives can be: 1. To have in-depth orientation on cause, spread and prevention of AIDS and related diseases. 2. To develop positive attitude towards HIV/ AIDS patients, so as to ensure their proper care. 3. To understand psychosocial aspects of human sexuality. 4. To sensitize and educate clinicians to the effectiveness and benefits of counselling.

2

Objectives (specific objectives will depend on the role in the field of AIDS preventive education as each discipline is a separate one and has specific job responsibility) 4

Persons/groups responsible—trained key-trainers from

Methods of training

5

General (for all) — Medical college • Lecture/discussion 1. Skills to handle HIV faculty. with video films, + v e / A I D S cases with — Hospital and clinic filmstrips and slides. compassion, care and administrators. • Seminars/workshops. understanding. — Private practitioners • Case history 2. Understand the and family physicians, discussion. psycho-social aspects — Staff of other • In-service orientation in counselling AIDS training institutes, training with skill patients. e.g. nursing and demonstration for 3. Types of sexual social science institutes, specific objectives. behaviour. — Any committed volun- • Special manuals on 4. Range of normality in tary agency/workers. AIDS and HIV. sexual behaviour. — Paramedical and non5. Psychological aspects medical health workers. of abnormal sexual — Medical and social behaviour. science staff of blood 6. Guidelines on safer banks. sex. (Contd.)

3

Stress on (content; details of groups would differ from one discipline to another)

Group 1: Professional Groups

Table 11. a

01

oo

jg <~>

Objectives

1. Advantages of happy married life and its positive effects as role modelling for adolescents and teenagers in the family. 2. Regular and correct use of condoms. 3. Advantages of a monogamous relationship. 4. Dangers of selfmedication, treatment by quacks, treatment with spurious drugs. 5. Dangers of casual sexual encounters. 6. Motivate for sex education to younger groups. 7. Importance of selected antenatal blood tests in pregnant mothers.

Stress on (for effective prevention, parents must be reached before and after they become parents)

Group 2.1: General Population

Table 11. b

-Welfare agencies. -Mahila Mandals. -Govt, agencies. -Responsible citizens. - Religious organizations. -Counselling agencies and centres. -Social clubs. -Health and welfare organization. -Family physicians and general practitioners.

of education

• Mass media, TV, radio, newspaper, films, etc. • Public lectures. • Informative discussions and talks in small groups with relevant audiovisuals. • Small informative booklets and leaflets. • Posters for awareness. • Individual guidance with audio-visual aids.

Methods

Medical and social science staff of factories and industries. Medical and social science staff in Dept. of Tourism. Medical and social science staff in hotels.

Persons/groups responsible—trained key-trainers from

7. Issues of confidentia- — 5. To be able to act as a lity. successful key-trainer for providing preventive 8. Blood transfusion only AIDS education to other in absolute need. — groups. 9. Pre-and post-test counselling. 6. Ability to discuss sexual Medical & Paramedical — matters in a frank and Group unembarrassed manner. 1. Recognise clinical 7. To develop non-judgesymptoms. mental attitudes. 2. Take sensible 8. To impart complete precautions when treatand full knowledge ting AIDS patients. about use and advantages of sex 3. To follow proper education in prevention sterilization procedures of venereal diseases when giving injections. /STDs. 4. Prevention of accidental spread—self and others. 9. To have basic skills in Non-Medical communication and 1. Promotion of counselling counselling. skills. 10. To understand the fact 2. Greater awareness of that prevention is a how behaviours are public health problem changed. and needs multi-pronged attack by all disciplines 3. Rehabilitation of and at all levels. patients. 4. Dealing with the uninfected spouse.

-Young population, 1. To provide full knowledge about STDs including AIDS, couples. its spread, prevention and -Parent groups. type of morbidity. -Community groups. -Religious leaders. 2. Change the attitude of social stigma attached to STDs. 3. To understand the dangers of promiscuity in sexual life. 4. To increase knowledge about safer sex and use of condoms. 5. To demand use of sterile needles, syringes when receiving injection a n d / o r blood transfusion. 6. To avoid tattooing and scarification, if instruments not properly sterilized. 7. To understand and appreciate the need for sex education for younger population. 8. To understand the necessity of regular health check-ups with investigations.

Type of groups (adult population)

-Committed voluntary workers. -Youth leaders. -Religious leaders. -Others.

- Teachers.

— Social workers.

Table 11. a (Contd.)

vi

co

w n

O Tl > 5

in

rr1 tZn o

X >

n

o aso

Objectives

1. Advantages of happy married life and its positive effects as role modelling for adolescents and teenagers in the family. 2. Regular and correct use of condoms. 3. Advantages of a monogamous relationship. 4. Dangers of selfmedication, treatment by quacks, treatment with spurious drugs. 5. Dangers of casual sexual encounters. 6. Motivate for sex education to younger groups. 7. Importance of selected antenatal blood tests in pregnant mothers.

Stress on (for effective prevention, parents must be reached before and after they become parents)

Group 2.1: General Population

Table 11. b

-Welfare agencies. -Mahila Mandals. -Govt, agencies. -Responsible citizens. - Religious organizations. -Counselling agencies and centres. -Social clubs. -Health and welfare organization. -Family physicians and general practitioners.

of education

• Mass media, TV, radio, newspaper, films, etc. • Public lectures. • Informative discussions and talks in small groups with relevant audiovisuals. • Small informative booklets and leaflets. • Posters for awareness. • Individual guidance with audio-visual aids.

Methods

Medical and social science staff of factories and industries. Medical and social science staff in Dept. of Tourism. Medical and social science staff in hotels.

Persons/groups responsible—trained key-trainers from

7. Issues of confidentia- — 5. To be able to act as a lity. successful key-trainer for providing preventive 8. Blood transfusion only AIDS education to other in absolute need. — groups. 9. Pre-and post-test counselling. 6. Ability to discuss sexual Medical & Paramedical — matters in a frank and Group unembarrassed manner. 1. Recognise clinical 7. To develop non-judgesymptoms. mental attitudes. 2. Take sensible 8. To impart complete precautions when treatand full knowledge ting AIDS patients. about use and advantages of sex 3. To follow proper education in prevention sterilization procedures of venereal diseases when giving injections. /STDs. 4. Prevention of accidental spread—self and others. 9. To have basic skills in Non-Medical communication and 1. Promotion of counselling counselling. skills. 10. To understand the fact 2. Greater awareness of that prevention is a how behaviours are public health problem changed. and needs multi-pronged attack by all disciplines 3. Rehabilitation of and at all levels. patients. 4. Dealing with the uninfected spouse.

-Young population, 1. To provide full knowledge about STDs including AIDS, couples. its spread, prevention and -Parent groups. type of morbidity. -Community groups. -Religious leaders. 2. Change the attitude of social stigma attached to STDs. 3. To understand the dangers of promiscuity in sexual life. 4. To increase knowledge about safer sex and use of condoms. 5. To demand use of sterile needles, syringes when receiving injection a n d / o r blood transfusion. 6. To avoid tattooing and scarification, if instruments not properly sterilized. 7. To understand and appreciate the need for sex education for younger population. 8. To understand the necessity of regular health check-ups with investigations.

Type of groups (adult population)

-Committed voluntary workers. -Youth leaders. -Religious leaders. -Others.

- Teachers.

— Social workers.

Table 11. a (Contd.)

vi

co

w n

O Tl > 5

in

rr1 tZn o

X >

n

o aso

1

Adolescents. Teenagers. Young adults. Young engaged couples. — Out-of-school youth in urban slums.

3

Table 11. c (Contd.)

1. To encourage a sense of personal responsibility rather than fear. 2. Acceptance of sex as good, healthy and necessary aspect of life. 3. Responsibilities of marriage and parenthood. 4. Suggestions and guidance in accepted social and moral codes. 5. Reinforce the existing safe behaviour of Indian youth (avoid pre-marital sex, have monogamy in marriage, no intimate behaviour with strangers and unknown people, etc.). 6. Dangers of indiscriminate sexual activity and casual affairs.

5. To help young people to face 7. What behaviour does and solve problems, if any. and what does not cause 6. To help them to approach STDs and AIDS virus marriage with knowledge, infection. understanding and with 8. Avoidance of risk certain values. behaviours. 7. To appreciate the value 9. Homosexuality, of committed relationship prostitution, drug with one individual. addiction, etc. Role in 8. To help young people to spread of STDs and achieve satisfying, lasting AIDS. and responsible interpersonal relationship. 9. To make them realise the importance of pre-marital consultation and medical examination, including HIV testing, for few (high risk). 10. To demand use of sterile needles, syringes, when receiving injection and/or blood transfusion. 11. To avoid tattooing and any scarification, if instrument not properly sterilized.

2

1. To remove ignorance, fear, superstition and unwholesome ideas about reproduction and to replace them with accurate information. 2. To help young people during the period of puberty to understand the changes—physical and emotional—which are taking place within them. 3. To provide scientific information on human reproduction that is both precise and clear. 4. To fully understand cause, spread and prevention of STDs including AIDS and current thinking about the disease syndrome.

4

Teachers. Social workers. Youth leaders. Trained peer groups. Yuvak Kendra members. Voluntary workers. National social service volunteers. Parents. Family doctors. Youth clubs members for out-of-school youths in slums. Staff of urban health post.

4

3

2

1 — — — —

Persons/groups responsible—trained key-trainers from

Stress on

Objectives

Type of groups

Group 2.2 : Young Population

Table 11. c

5

of education

5

(Contd.)

• Question-answer and quiz sessions. • Individual counselling and guidance. • Group discussion with audio-visual aids. • Well made films with scientific information. • Role-plays. • Guided lecture/ discussion with audio-visual aids. • Special manuals on AIDS with diagrams.

Method

Z

o m O Tl > 3

n > rr rr:

oo

00

1

Adolescents. Teenagers. Young adults. Young engaged couples. — Out-of-school youth in urban slums.

3

Table 11. c (Contd.)

1. To encourage a sense of personal responsibility rather than fear. 2. Acceptance of sex as good, healthy and necessary aspect of life. 3. Responsibilities of marriage and parenthood. 4. Suggestions and guidance in accepted social and moral codes. 5. Reinforce the existing safe behaviour of Indian youth (avoid pre-marital sex, have monogamy in marriage, no intimate behaviour with strangers and unknown people, etc.). 6. Dangers of indiscriminate sexual activity and casual affairs.

5. To help young people to face 7. What behaviour does and solve problems, if any. and what does not cause 6. To help them to approach STDs and AIDS virus marriage with knowledge, infection. understanding and with 8. Avoidance of risk certain values. behaviours. 7. To appreciate the value 9. Homosexuality, of committed relationship prostitution, drug with one individual. addiction, etc. Role in 8. To help young people to spread of STDs and achieve satisfying, lasting AIDS. and responsible interpersonal relationship. 9. To make them realise the importance of pre-marital consultation and medical examination, including HIV testing, for few (high risk). 10. To demand use of sterile needles, syringes, when receiving injection and/or blood transfusion. 11. To avoid tattooing and any scarification, if instrument not properly sterilized.

2

1. To remove ignorance, fear, superstition and unwholesome ideas about reproduction and to replace them with accurate information. 2. To help young people during the period of puberty to understand the changes—physical and emotional—which are taking place within them. 3. To provide scientific information on human reproduction that is both precise and clear. 4. To fully understand cause, spread and prevention of STDs including AIDS and current thinking about the disease syndrome.

4

Teachers. Social workers. Youth leaders. Trained peer groups. Yuvak Kendra members. Voluntary workers. National social service volunteers. Parents. Family doctors. Youth clubs members for out-of-school youths in slums. Staff of urban health post.

4

3

2

1 — — — —

Persons/groups responsible—trained key-trainers from

Stress on

Objectives

Type of groups

Group 2.2 : Young Population

Table 11. c

5

of education

5

(Contd.)

• Question-answer and quiz sessions. • Individual counselling and guidance. • Group discussion with audio-visual aids. • Well made films with scientific information. • Role-plays. • Guided lecture/ discussion with audio-visual aids. • Special manuals on AIDS with diagrams.

Method

Z

o m O Tl > 3

n > rr rr:

oo

00

of groups

-Prostitutes and their clients. -Patients of STD clinics. -Homosexual and bi-sexual men. -Addictive drug users. - J a i l inmates. - Haemophilics and thalassaemic patients. -Tourists and tourist industry. -Sailors, seamen and maritime workers. -Others: frequent travellers, diplomats from high risk areas, etc. -Professional blood donors.

Type

-Women of childbearing age. -Pregnant and lactating mothers.

Type of groups

-Antenatal, post-natal and well-baby clinic staff. -Medical and paramedical staff. -Trained dais. - Multi-purpose workers. -Voluntary health workers. -Urban health post staff. -Private practitioners.

Persons/groups responsible—trained key-trainers from

Each group would need to be exposed to specific problems of the group. 1. Personal habits and hygiene. 2. Menstrual hygiene and disposal of soiled material and articles. 3. Use of condoms. 4. Responsibility of an infected partner towards the spouse. 5. Guidelines for safer sex. 6. Pre and post-test counselling.

Stress on

—Voluntary workers. — Social organizations. — Self-help groups. — Municipal health organization. — STD clinic staff. — Special voluntary organizations for specific groups. — Peer group counselling. — Urban health post staff. — Local private practitioners.

Persons/groups responsible—trained key-trainers from

Group 3: High-Risk Behaviour Group

1. To understand fully cause, spread and prevention of AIDS related diseases. 2. To increase knowledge about safer sex. 3. To demand use of condoms at each sexual exposure. 4. To be able to appreciate the importance of change in behaviour. 5. To avoid having many sexual partners. 6. To appreciate the safety and importance of safe sexual activity with spouse. 7. To maintain good personal and menstrual (in females) hygiene.

Objectives

1. Training women in usefulness of motivating partner to use condoms. 2. Importance of selected antenatal blood check-ups.

1. All the objectives listed under general population groups. 2. Additional information related to "motherchild dyad" transmission. 3. Knowledge about methods of infection, prevention and use of condoms.

Table 11. e

Stress on

Objectives

G r o u p 2.3: Vulnerable Groups

Table 11. d

of education

of education

• Individual guidance with audio-visual aids. • Small group (five to ten individuals) guided discussion with audio-visual aids. » Demonstration of condom use and its disposal after use. > Information handouts. • Lecture/discussion with films, filmstrips. • Slide shows. 1 Dramas.

Method

> At antenatal, post-natal and wellbaby clinics. > Group discussion with audio-visual aids. > Individual guidance with audio-visual aids. > Lecture/discussion with TV and video films. > Talks with slide shows.

Method

of groups

-Prostitutes and their clients. -Patients of STD clinics. -Homosexual and bi-sexual men. -Addictive drug users. - J a i l inmates. - Haemophilics and thalassaemic patients. -Tourists and tourist industry. -Sailors, seamen and maritime workers. -Others: frequent travellers, diplomats from high risk areas, etc. -Professional blood donors.

Type

-Women of childbearing age. -Pregnant and lactating mothers.

Type of groups

-Antenatal, post-natal and well-baby clinic staff. -Medical and paramedical staff. -Trained dais. - Multi-purpose workers. -Voluntary health workers. -Urban health post staff. -Private practitioners.

Persons/groups responsible—trained key-trainers from

Each group would need to be exposed to specific problems of the group. 1. Personal habits and hygiene. 2. Menstrual hygiene and disposal of soiled material and articles. 3. Use of condoms. 4. Responsibility of an infected partner towards the spouse. 5. Guidelines for safer sex. 6. Pre and post-test counselling.

Stress on

—Voluntary workers. — Social organizations. — Self-help groups. — Municipal health organization. — STD clinic staff. — Special voluntary organizations for specific groups. — Peer group counselling. — Urban health post staff. — Local private practitioners.

Persons/groups responsible—trained key-trainers from

Group 3: High-Risk Behaviour Group

1. To understand fully cause, spread and prevention of AIDS related diseases. 2. To increase knowledge about safer sex. 3. To demand use of condoms at each sexual exposure. 4. To be able to appreciate the importance of change in behaviour. 5. To avoid having many sexual partners. 6. To appreciate the safety and importance of safe sexual activity with spouse. 7. To maintain good personal and menstrual (in females) hygiene.

Objectives

1. Training women in usefulness of motivating partner to use condoms. 2. Importance of selected antenatal blood check-ups.

1. All the objectives listed under general population groups. 2. Additional information related to "motherchild dyad" transmission. 3. Knowledge about methods of infection, prevention and use of condoms.

Table 11. e

Stress on

Objectives

G r o u p 2.3: Vulnerable Groups

Table 11. d

of education

of education

• Individual guidance with audio-visual aids. • Small group (five to ten individuals) guided discussion with audio-visual aids. » Demonstration of condom use and its disposal after use. > Information handouts. • Lecture/discussion with films, filmstrips. • Slide shows. 1 Dramas.

Method

> At antenatal, post-natal and wellbaby clinics. > Group discussion with audio-visual aids. > Individual guidance with audio-visual aids. > Lecture/discussion with TV and video films. > Talks with slide shows.

Method

Objectives

1. To understand fully cause, spread and prevention of A I D S / H I V for safety of close contacts. 2. Practice sexual abstinence or use of condom at each sexual exposure. 3. To avoid pregnancy. 4. To practice daily relaxation. 5. To maintain balanced and wholesome diet. 6. To avoid and take precaution against opportunistic infections. 7. To maintain proper personal and menstrual (in females) hygiene. 8. To resolve immediate concerns—personal, social, financial and familial.

Type of groups

— Prostitutes. — STD clinic patients. — Professional blood donors. — Frequent blood transfusion users, e.g. haemophilics, etc. — IV drug users. —Jail inmates. — Spouses of AIDS patients. — Others.

1. The dangers of repeated infections. 2. Counselling concern of getting full-blown AIDS. 3. Concerns of disfigurement and death. 4. Family concerns about finances, children, etc. 5. Personal and practical support from the community and health services. 6. Safe sexual practices, or sexual abstinence. 7. Disposal of soiled material and articles (pads, syringes, used condoms, etc.). 8. Relaxation exercises. 9. Meditation with specific groups. 10. Problem-solving and crisis management.

Stress on

Family doctors. Health educators. AIDS counsellors. Trained peer groups. Self-help groups. Voluntary workers. Community groups. Parent/family groups. Self-help support groups by the families of the HIV +ves. — Urban health post staff. — Local private practitioners. — Peer groups.

— — — — — — — — —

of education

• Individual counselling with one-to-one approach. • Group counselling with audio-visual aids. • Peer group counselling with aids. • Films on video and TV. • Slide shows. • Role-plays.

Persons/groups responsible Method —trained key-trainers from

Group 4: H I V Positive and AIDS Patients

Table 11. f

I EC

93

outline regarding education and counselling for AIDS prevention. Four major target groups were identified and modules were proposed for each group separately. These are not only informative but extremely useful in the present context. Therefore, they are reproduced in Tables 11 a,b,c,d,e and f. What is Counselling Since the beginning, mankind has practised counselling in one form or the other. Parents, teachers and peers have been natural counsellors. Professional counsellors came about to fulfil a special need of some groups of people.There are student counsellors or marriage counsellors and the like. Advent of AIDS gave an extraordinary significance to the concept of counselling. Counselling is a process that can help people to understand and deal with problems and to communicate better with those with w h o m they are emotionally involved. In counselling, people—not related to one another — m e e t to resolve a crisis, solve a problem or make decisions involving very personal and intimate matters and behaviour. It can motivate people to change their behaviour patterns and teaches them to deal with fear and/or anxiety. Pre-test counselling is used to ensure that individuals desiring or consenting to be tested for HIV infection are well informed and aware of the technical, social, legal, ethical and economic implications of testing. Post-test counselling (preferably to include seronegatives and 'at risk' groups also) is designed to : • • • •

assist 'clients' to accept and act upon information on their health status propose realistic action adapted to different risk situations and circumstances provide support at times of crises encourage a change in behaviour for prevention or control of spread of infection

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The Government of India and some state governments are contemplating training a large number of counsellors, especially for STD, AIDS and related health problems. As a service, it is hoped that this will be a sustainable programme. It is essential that people requiring counselling are ensured of continued access to the counsellors and consistent support from the health and social system. The most important point concerns time. Counsellors should be able to spare sufficient time not only to talk but also to listen, so as to facilitate problem solving. Thus, training alone will not help unless the trained are continuously available. Legal, Ethical Issues and Dilemmas In general terms, law is expected to ensure social justice to protect society while ensuring order, support for fundamental human rights and, at the same time, preserve and protect the public good. Ethics on the other hand is a series of guidelines derived for a specific group to ensure their correct and good behaviour in respect of their profession or workplace. It is related to colleagues and other persons that they come in contact with during the performance of their (professional/workplace) duties and activities. Since an element of good versus bad is involved, ethics is associated with morality. Thus, an action may be perfectly legal and yet be considered immoral by a certain group of people. Ethics, in very simple terms, is a moral code of conduct. It might seem that overall, 'medical ethics' conveys that it is the power conferred to cure and control. It is desirable to replace the word 'power' with the word 'knowledge'. All medical, paramedical, technical, nursing and other staff providing health care are called health care workers (HCWs). According to Dr Eustace J. D'souza, Executive Director, F.I.A.M.C., Bio-medical Ethics

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Centre, Bombay, every HCW should follow three primary ethics : • • •

The ethic of LOVE The ethic of TRUTH The ethic of DO NO HARM

To heal the sick, alleviate suffering, promote health and prevent the spread of the disease are components of the first. HCWs should maintain strict confidentiality regarding patients' illnesses and information imparted in confidence during consultancy. At the same time, they should respect patients' rights and give the correct information about their health status. The 'do no harm' ethic is obviously important. It should also include taking all sensible safety precautions to prevent the spread of infection. A basic concept is developed in HIV prevention, that is called universal precaution. It is neither practical nor ethical to test every single patient for HIV. Blood and sexual fluids are the major vehicles carrying the virus. Therefore, the best policy for HCWs is to handle every single blood specimen (sexual fluids, if handled) with care and precautions as if it were infectious. This means that a habit needs to be inculcated ;o as to control the spread of the virus. Patients' rights were mentioned earlier. They also have obligations. A very important ethic for them is 'do no harm'. They should not perform any negligent act that can spread HIV/AIDS to others. In fact, Section 269 of the Indian Penal Code has a provision for negligent act likely to spread infection of disease dangerous to life. This is punishable with imprisonment extending to six months, a fine or both. This Section was provided during the British rule to protect against plague, cholera, etc. It is understood that this was also implemented. There is also a Section 270 which mentions "malignant act likely to spread infection of disease dangerous to life" with imprisonment of two years or a fine or with both.

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down under the Drugs and Cosmetics Act. This is a punitive legislation meant to punish those who commit the offences. Formulated with an intention of cleaning up blood banking and transfusion services, these it is hoped, do not prove counterproductive by discouraging even some conscientious blood banks. United Nations Development Programme (UNDP), Division of Regional Bureau for Asia and the Pacific had in 1993 held intercountry consultation on 'Law, Ethics & HIV.' Advocates, those connected with teaching of law and judiciary, participated in this consultation. All countries of the region including India were represented; proceedings of this consultation have been published by the UNDP. In the final analysis, a major consideration for laws should be that they should, in actual practice fulfil the function that is intended. In this instance, it should be to control the spread of HIV and AIDS. It is interesting to note that the concluding 'statement of belief' endorsed by the participants of legal profession was not much different from what might have been endorsed by other groups concerned with socio-cultural and ethical issues related to HIV/AIDS (Appendix 2). Dilemmas arise in blood banks, and hospital/medical practices. In blood banks, the ethics regarding disclosure of HIV status to the respective blood donors is, as a rule, not followed. The reason is that a single ELISA reactive blood unit is discarded without confirmation. In view of this somewhat incomplete testing (with the main objective of safety of recipients in mind), no donor is informed for the fear that the result might be 'false positive' and may create unnecessary panic in a truly uninfected individual. If, however, the person is in fact infected, but is not informed, he/she may continue unsafe sexual practices and may add to the chain of transmission. 'To tell or not to tell' is indeed a dilemma. If a patient refuses to inform his/her spouse of his/her HIV-seropositive status, should the doctor do so, thus breaking 'confidentiality'

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The three basic tenets of ethics should also be applicable to patients' spouses, family members, community and the society. There is a need for provision for anti-discrimination. No person should be discriminated in education, employment, housing, travel or any community services or benefits on the ground of his or her HIV positive status. Here, too, dissemination of information and imparting correct knowledge may be more beneficial than a legislative measure alone which is implemented infrequently. The one legislative measure urgently needing enforcement concerns mandatory screening of all blood donors for HIV and hepatitis B virus, irrespective of whether they belong to the category of professional/paid or voluntary donors. This introduces an ethical issue regarding 'informed consent' of these donors. It should not be difficult to ensure that every donor is made aware that HIV screening will be done routinely before the blood can be accepted for transfusion. The condition for compulsory testing should be incorporated while giving licences to all blood banks including the vast number of small, private ones. There should be appropriate and, if necessary, separate legislation regarding manufacture of blood products including mandatory testing of their paid donors. At the same time, technical recommendations made by the national authority should be scientifically and technically sound and equivalent to the international standards. There is also a need to encourage and support manufacture of indigenous products of good standard quality. Many of these are required continuously for the survival of patients suffering from blood disorders, such as haemophilia and thalassaemia. Very recently, Directorate of Health Services, Government of Maharashtra has formulated and publicized a legal framework for regulations of use of the whole blood. The advertisement mentions offences and penalties as laid

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or, should he remain silent and thus place the other partner at risk? Yet another dilemma in hospital emergency services confront doctors. After large-scale accidents or due to emergency requirements to treat severe bleeding (during delivery or some surgery), unexpectedly large number of blood units may be required. A situation may arise leaving no time for screening of blood donors. Should a doctor give unscreened blood with a potential danger to the recipient, or should he play safe and refrain from transfusion of unscreened blood? What order of priority should doctors allot between requirements of those who are HIVinfected and those who are not? Another dilemma concerns advice that needs to be given to HIV-infected women who have become pregnant. Knowing that in general, the virus is passed only to about 25 per cent of babies born of infected mothers, is the doctor justified in advising medical termination of the pregnancy? Many such dilemmas will increasingly face our doctors who will have to play God. Socio-Economic Issues : Fundamentally, AIDS should be viewed as a crisis in public health which has some important human rights dimensions. Viewed thus, it brings out a commonality with other public health problems, many of which are precipitated under low socio-economic conditions. Indeed, the poor and the ignorant are powerless; they are the ones who encounter various physical and social risk factors. This aspect has been well depicted by Wallerstein (Box 3). To these people, stigma and social exclusion are neither new nor linked with AIDS alone. They undergo a variety of infectious diseases and suffer from nutritional deficiencies. Their fight is not for human rights but, for their very survival. It is a matter of supreme indifference to them whether they die of AIDS, TB, gastroenteritis or pneumonias. Poverty and ignorance are significant factors which aid and abet HIV and AIDS.

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Box 3 Physical and Social Risk Factors

Living in poverty L o w in hierarchy High demand Psychological Physical L o w control Perceived :

External locus learned helplessness

Actual :

No decision making Lack of e c o n o m i c / political power

Chronic stress Lack of social support Lack of resources

Wallerstein N., 'Powerlessness, Empowerment, and Health : Implications for Health Promotion Programs,' Am. ]., Health Promotion, 6(3) : 197-205, 1992.

The poor are even denied compensation for negligence against hospitals/doctors as was recently decided by the Consumer Court. The reason given was that the treatment given was free of cost (Box 4). Whether poor or not, women are extremely vulnerable because of their powerlessness to influence their husbands' sexual behaviour. One may almost say that marriage itself can become a risk factor for some women. They lack the decision-making powers about the use of condoms as protection against AIDS or for other contraceptives.

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Box 4 HIV Woman Treated Free Loses Compensation Suit A woman went in for corrective heart surgery in Wanless Hospital which is a charitable hospital. After the operation, her blood pressure dropped and more blood was given to her. The first three units of blood were HIV tested but due to the grave emergency of her situation, the fourth unit of blood given to her was not HIV tested. This fourth unit of blood resulted in her getting infected with HIV since blood was found to have HIV virus. The HIV-infected woman passed on the infection to her child. Consequently, she filed-for compensation of Rs 10 lakhs in the Consumer Court. The Consumer Court held that since the case concerned a charitable hospital and she was treated free of cost, she could not be paid compensation for negligence. The implication one draws from this ruling is that charitable organisations can perform grave acts of negligence with impunity as they will not be liable under Consumer Protection Act, 1986. The only remedy available to the affected person would be to file a suit under the law of torts for negligence—The Lawyers, June 1994, p. 30.

It is now increasingly being recognized that amongst the important risk factors, the pride of place (dubious) should be given to socio-economic factors and the lack of sexual/reproductive decision-making for women. Strategies to improve these conditions will include long-term measures. However, these are crucial in reducing the spread of HIV and should be undertaken immediately. There is a potential for appropriate legal reforms. It is generally believed that law in any form is an important expression of social and cultural values. It can therefore be used to change these values. A beginning seems to have been mad^ in this direction, as recently the Supreme Court struck down Section 309 of the Indian Penal Code and decided that an attempted suicide should no more be considered a crime. The court felt that suicide was not against religion, morality or public policy and had no

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harmful effect on the society. This judgement has drawn comments from a variety of persons. Among them, a statement by Dr Eustace D'souza is reproduced here: "They certainly embarked on a landmark departure from tradition, entering a new and social dimension for concern for the emotionally burdened individuals where penal actions only added insult to injury." (Times of India, Sunday Review, 17 July, 1994). The other side of the coin of economy is the effect of AIDS on economic conditions of an individual, family, society and ultimately, the nation itself. The fact that this disease syndrome affects the most productive segment of society (age 15 to 35), is debilitating and ultimately fatal makes it a potent threat to the country's economic growth and development. Mr P.R. Dasgupta, the chief of NACO had earlier presented a tragic scenario of the economic impact of HIV/AIDS. 1 1 Cultural Impact12 : Our culture is something that surrounds us and is a part of us. It is linked with this land on which we have been living over thousands of years. It has a past, a glorious one of which we are proud. But it also has a present, and what we do now, will determine the future. Attempts have been made to link our cultural heritage with the fight against AIDS. In this context, use of scriptures and spiritualism would be most apt. For example, our Bhagavad Gita represents a classic case of one-to-one counselling. A battle is raging not only outside but is also reflected in Arjuna's mental condition. Krishna, the counsellor, takes time off in the midst of the battle(s). He explains to Arjuna the whole philosophy of life. He listens to Arjuna's 11

12

Further reading : CARC Calling 6(1) : 30, 1993 for Mr Dasgupta's speech. Further reading : AIDS Prevention : The Socio-Cultural Context by Dr Purnima Mane and Ms Shubhada A. Maitra, 1992, published by Tata Institute of Social Sciences, Bombay.

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queries, appreciates his anxieties and also the stand taken by Arjuna. He answers, he explains, but, ultimately Krishna leaves it to Arjuna to do exactly what he chooses to do. Indeed, there is a subtle though profound message in it for us. It teaches man to consider alternatives, to appreciate that each action has a reaction and, then to choose the good, which is realized by a conscious personal effort. In this connection, let us recall what our Prime Minister P.V. Narasimha Rao, the then Minister of Human Resources Development, Health and Family Welfare, said at the 40th Health Assembly (WHO) in Geneva: "The indigenous traditions of almost all countries have always contained a common reservoir of wisdom which prescribes as well as prohibits certain human actions and behaviour for common as well as individual well-being. A large part of this wisdom concerns public health. The revival, amplification and strengthening of this traditional wisdom is becoming more and more essential with every passing day."

Appendix 2

UNDP Intercountry Consultation on Law, Ethics and HIV Statement of Belief13 —

We believe that every individual has a right to dignity, health and life. Public health and the interests of the community in the context of the HIV epidemic depend upon respect for individual rights and recognition of the worth of each member of our societies.

—

We acknowledge that we are all likely to be affected by the HIV epidemic.

—

We believe that the law must promote an environment that enables, encourages and sustains voluntary behaviour change and the care and support of those affected. This requires the empowerment of individuals and communities to protect themselves against HIV, and that people living with HIV remain integrated within society and free from all forms of discrimination.

—

We affirm that it is the responsibility of each individual, community and nation to take up this cause through existing means of advocacy and by creating new ones. We must express and act upon a concern for ourselves and others.

—

We recognize that the subordinate position of women within their families and communities makes them

13

This statement was drafted and endorsed by the participants at the 'UNDP Intercountry Consultation on Law, Ethics, and HIV', held in Cebu, Philippines, 3-6 May, 1993.

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particularly susceptible to HIV infection. Social structures, laws and practices, as well as values and attitudes, must change to improve the status of women. —

We believe that the development of effective responses to the HIV epidemic requires, above all, the active participation of people affected by the epidemic, as well as the building of partnerships amongst communities, governments and the legal, health and other professions.

10

AIDS V E R S U S US, T H E PEOPLE OF INDIA 40. ajnas ca sraddadhanas ca sam'sayatma vina'syati na yam loko sti na paro na sukham sam'sayatmana 40. "But the man who is ignorant, who has no faith, who is of a doubting nature, perishes. For the doubting soul, there is neither this world nor the world beyond nor any happiness. We must have a positive basis for life; an unwavering faith which stands the test of life." —S. Radhakrishnan, on Bhagavad Gita Statistics such as one million, 2.5 million or even ten million persons in India being HIV-infected by 1995 may not disturb us much at present. As yet, we have personally not come across patients with AIDS. We do not realize what pains they have, what mental and physical sufferings they undergo before they end up looking like skin and bones. Many of us have seen or heard about cancer patients. They also have pains and often suffer much, ultimately to die. But cancer does not spread like AIDS which is caused by an infectious agent, the dreaded HIV. Just suppose one million persons have already been HIV-infected in India. Extrapolated to an approximate population of around 860 million, it would be (approximately) one person infected in every 1,000. Would this signify that anywhere in the country, if 1,000 persons from any group, community or society were to meet, there

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would be one HIV-infected person? No, it does not, because statistics rely on the law of averages. Take for instance, a crowd of 1,000 intravenous drug users in Imphal, Manipur. The number of HIV-infected in this group in this region will not be one per thousand but 400-500 for every thousand. Another example would be female commercial sex workers (prostitutes) in Bombay's 'red light' area. Here again, there might be around 300 HIV-infected persons for every 1,000 present. A crowd of say men frequenting STD clinics would also show up nearly 100200 HIV-infected persons for every 1,000. So what do these figures signify? Why are they necessary? Not actual figures but 'trends', as to the changing patterns in an area, are essential. They guide us to take intervention measures appropriate for that particular group in a particular region. Otherwise, these statistics are used mainly by media; they may be useful for politicians. For example, for population control, speaking of adding 'an Australia' to it every year would be impressive, although it does not tell us which region or which groups are most responsible for this phenomenon. In the absence of such definitive 'qualitative epidemiological data', it is difficult to plan appropriate intervention strategies targeted to the groups/communities, etc. who need them most. On the same 'Australia' analogy we may state that in the Bombay 'red light' area, even at the most conservative estimate (see Box 5), one man is infected every seven to eight minutes, it becomes more meaningful. Still more so if we show how each of these men are responsible in further extending the chain of HIV transmission (Fig. 8). The targets where maximum efforts are needed for intervention, i.e. breaking the chain of transmission, become clear—IV drug users in north-eastern India, female CSWs and, more particularly, men visiting them in Bombay and other parts of Maharashtra, as also others indicated through 'qualitative epidemiology', for example professional blood donors.

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Box 5 Estimate of HIV Infection Among Male Clientele of Female CSWs in 'Red Light' Area, Bombay (a conservative estimate) •

Two years ago, we had considered 60,000 CSWs of whom 25 per cent were estimated to be HIV infected. Current data indicate the total of 80,000 of whom 50 per cent is estimated to be HIV infected.

: The number of HIV infected CSWs would be 40,000

•

Each female on an average has six clients

: There would be 2,40,000 clients.

•

Not all these males would be uninfected; assuming 15 per cent of the male client to be already infected

: There would be 2,04,000 uninfected males.

•

If only 0.1 per cent of these 2,04,000 males aquired HIV infection

: There would be 204 infected every day. : There would be eight to nine males infected.

• Thus every hour OR

One male acquires new HIV infection seven to eight minutes.

For all of them, knowledge, even with its wide definition, is not enough. They need further support. Greatest attention needs to be paid to 15 to 35-year old men who create high risk situations. However, since it is easier, much of the current work of IEC is directed to commercial female sex workers. Indeed, what is most needed in this area is to empower women in various decision making. This should be included in long-term measures along with programmes to change lifestyle and behaviour patterns through knowledge, and IEC, where 'C' in the form of counselling should be stressed. For the present, fire-fighting measures will have to be continued in a much more accelerated, expanded way. These should include

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adequate provision of condoms and accurate information regarding their appropriate usage (Epilogue II), supply of bleach for cleaning and decontaminating needles and syringes may be a more practical, cost-effective alternative to the distribution of sterilized needles and syringes to all intravenous drug users. No emphasis can be enough to point out that these measures are short term, and may not be sustainable. In absence of any long-term planning, these are not cost-effective; ultimately, they become mere gestures. AIDS and Us What matters to us most is one single issue. How can we and our loved ones remain free of the wretched virus? In other words, how can I ensure, as long as it is in my hands, to continue to be excluded from that average of one (or more) of HIV-infected persons in every 1,000? You have read the previous chapters and are aware of many facts and features about AIDS and the virus. Be sure to remember how it spreads, and of course, how it does not. This way, we can concentrate on avoiding only those modes which are likely to convey HIV to us. Sexual mode is the most important, since it is the most frequent as compared to transfusion of infected blood or use of contaminated syringes and needles or reproduction (a major presumption is that you and I are not IV drug users). We know how the virus is acquired sexually, how it is helped further if we have other STDs. By now, we should know how to avoid it ; the risk, of course, is not in enjoying sex, it is in having it with an HIV-infected partner. A single intercourse with an infected partner may pass on the virus, but the probability increases with increasing intercourse. By having multiple partners, i.e. being promiscuous, we face a high risk situation. But if rome of us are unable to control this despite the risk, the

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DESPITE THE PLEASURE

109

THE CHOICE IS YOURS: BE SAFE AND HAPPY

AIDS IS A KILLER BEST PROTECTION IS A FAITHFUL MONOGAMOUS RELATIONSHIP

IT ALSO KEEPS YOUR MARRIAGE SAFE

PROTECT YOURSELF FROM AIDS

M A K E SENSIBLE A N D RESPONSIBLE S E X U A L DECISIONS

"AIDS? No Chancel I use a CONDOM

(HiAMVCM

^

vou AND^FMTNERS IN PREVENTION

,

avoid sex outside marriage

V

Fig. 21 : Some ways of ensuring that you do not get AIDS.

%

-t

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only recourse is to use condoms any time, every time, anywhere and everywhere during sexual intercourse, unless, you have only one faithful uninfected partner, who in turn, is faithful to you. Use of alcohol and drugs which may lead to a rash, risky behaviour should be avoided. The sure way of selfpreservation is to make the correct choice of a partner; if you still choose to be promiscuous, be wise and use condoms; in Fig. 21 are shown some of these alternatives. Female condoms are being tried in some countries including Thailand. But, they are not freely available yet. Therefore, only men will have to remember or will have to be reminded that condom sense is commonsense. Transfusion-associated transmission, i.e. through blood/ blood products is another important point. It is common knowledge that we do not acquire HIV if we donate blood at reliable blood banks. Always insist on checking if they are using new disposable or properly sterilized equipment for collecting your precious blood. Remember, screening for HIV will be done on your blood unit as also on all others. As per Fig. 22 and 23, you can get HIV/AIDS on receiving transfusion of infected blood, if the blood is not screened. Even when screened there is a possibility that the donor might be in 'window period' (Ch. 3). This danger exists with the so-called professional donors at high risk situation. This should be avoided by not using blood from such professional donors. How could it be done ? Remember the saying 'if you can't lick them, join them'; not to sell blood, but as a voluntary donor. Indeed, safety measures begin with a safe donor, only then come safe practices. There is no doubt at all that voluntary donor's blood is safer (not entirely safe unless screened). Instead of forcing blood banks to buy blood, form a habit to donate blood at least once, if not twice a year. If some doubt arises regarding the HIV status, a visit to the State

aids v e r s u s us, t h e people o f i n d i a

BLOOD TRANSFUSION (receiving

Blood

transfusion

blood)

can

become

111

BLOOD DONATION (giving t>looci) You

do

not

3et

AIDS

by

hazardous 'IF:

donating

• Blood has not been screened for HIV antibodies • Blood has b e e n p u r c h a s e d from professional b l o o d sellers

b l o o d banks, w h i c h use aseptic

*

blood

to

reputed

techniques

and

needles

transfusion

&

disposable sets.

D O N A T E B L O O D VOLUNTARILY: M A K E IT A HABIT. * Y O U D O N ' T K N O W W H E N Y O U W I L L N E E D IT. * CHECK THAT B L O O D IS NOT OBTAINED F R O M P R O F E S S I O N A L B L O O D SELLERS.

Fig. 22 & 23 : Show that H I V / A I D S can be contracted through trans fusion of infected blood.

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Surveillance Centre or a call on a referral laboratory could be arranged. In such circumstances (of a doubt), the only way is that of 'self-denial'; don't make the supreme gift of your blood. In the absence of any reasonable doubt, we need to donate this life-giving fluid freely; it also comes free to us. Patients of haemophilia or thalassaemia who require continuous treatment with blood products should, through their doctors, ensure that these are produced as per the standards laid down for their safety. HIV can also be transmitted through contaminated needles or syringes or other skin-piercing implements used for tattooing, acupuncture, etc. We will avoid sharing needles for drug abuse, but how to avoid the others? Insist always that disposable/sterilized syringes and needles are used by the health care providers. In India, rag-picking and reusing discarded material is a common practice. What if a disposable needle used on an HIV-infected person is reused without decontamination and sterilization? Although this is unlikely, it could occur if needles used for intravenous injections (direct contact with blood), were to be reused. Why take a chance on a false sense of security? Therefore, whenever visiting doctors, dentists, etc., check if proper care is taken for cleaning, sterilizing and discarding of all instruments. HIV is quite fragile outside the body; it gets easily killed by heat. Boiling for 15 minutes is a sure way to kill it. If boiled properly, the virus is destroyed in a minute or two. From intact skin, we can wash it off with soap and water. In dry state outside the body, it does not last long. In liquid state it may remain viable for a few days, but if any blood or sexual fluid is treated with ordinary bleach, it is sufficient to kill the virus within an hour or so. Therefore, routine precautions of washing, cleaning, boiling or heat under pressure (pressure cookers, autoclaves) are sufficient to destroy the virus. Health care workers in hospitals are also being provided the required

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knowledge on biosafety measures as shown in the module 11a. in Ch. 8. The virus can pass from an infected mother to the child, during pregnancy and childbirth. In our country with rapid heterosexual spread, more women will be infected, thus placing unborn children at high risk situations even before they are born. One advice could be to use condoms all the time and avoid birth. It has to be decided by the couple. What is known is that one in every three HIV-infected women could pass the virus on to

Fig. 24 : Several do's and don'ts to avoid contracting HIV/AIDS.

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infants. This could be higher in Pattern II and III countries and lower among mothers from the Pattern I countries. If a child is born, breast-feeding is recommended irrespective of HIV status of the baby. This is because of numerous advantages of breast-feeding as described (Epilogue II). To conclude, several do's and don'ts shown in Fig. 24 should enable us to avoid HIV/AIDS. Figs. 1, 2, 3, 5, 6, 13, 14, 20, 21, 22, 23 and 24 are reproduced from the exhibition panel prepared by the ICMR Centre for AIDS Research and Control (CARC), Bombay.

10

CONCLUSION, BUT NOT T H E END OF THE STORY "The history of AIDS is telling us something very important about the disease in the modern world. The tragedy of AIDS will be greater if we fail to heed the global lesson." —Dr Jonathan Mann The story of AIDS, a new disease of the modern world, is telling us many things and not only of a medical entity. It tells us about social, ethical, legal, economic, psychological and spiritual issues as well. Like environment, it teaches us to think globally but act locally. This tragic tale is trying to teach us—perhaps, not too successfully— to think not of us and them, the HIV-infected, but of all of us. It has opened up channels of more effective communication between government and non-governmental agencies like no other disease did. AIDS has created panic and degrading discrimination on the one hand, and on the other, it has brought to light heroic support and understanding from partners/spouses, families, friends and entire communities. In fact, this support has been one silver lining among the ominous clouds surrounding PWAs. The role of community as a pivot had been appreciated so that the WHO had declared the World AIDS Day for 1992 as AIDS: A Community Commitment. The World AIDS Day is observed every year on 1st December (Box 6). In 1991, the theme was 'Sharing the Challenge'.

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Box 6 December 1—World AIDS Day* World day to world brings

AIDS Day is not a day of statistics and numbers but a realize that each person infected or ill is a person with a of family and friends around them. World AIDS Day us a little closer to our humanity—in a world with AIDS.

It is not too early to start thinking about World AIDS Day, 1994, which has been designated the International Year of the Family. As AIDS represents an increasingly heavy burden for millions of families around the world, the World Health Organization (WHO) is proposing to link World AIDS Day with all the other activities which will be undertaken worldwide for the Year of the Family. World AIDS Day is being observed on 1 December since 1988. This year it will be the Seventh World AIDS Day. World AIDS Day

Year

Theme

First Second Third Fourth Fifth Sixth Seventh

1988 1989 1990 1991 1992 1993 1994

Global mobilization against AIDS AIDS & youth Women & AIDS Sharing the challenge AIDS—a community commitment Time to act AIDS & the family

*N.C. Jain : CARC Calling, 7(2) : 61, 1994.

People all over the world participated in many events. Partnerships of all kinds were formed globally to fight the common enemy—AIDS. 1 December, 1994 will be marked 'AIDS and the Family'. This will include personal relationships and social 'families' of every kind, as well as more traditional family units. On the technical side, rapid strides have been made in a variety of biomedical and biotechnological areas. Due to the vision of some scientists, development of strategies for effective application of technological advances have

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almost kept pace with the technological advances. Many have been in the race for monetary gains, but, a number is driven by determination to solve the enigma of AIDS. Tracing its history will guide humanity to tackle other emerging epidemics of future. In his inaugural speech at the First National Conference on AIDS in Bombay on 28-29 March, 1992 jointly held by the Society for Prevention of AIDS (SPA) and the Directorate of Health Services of Maharashtra, Prof. V. Ramalingaswamy stated : "Finally, we must turn the prospects of a disaster into an exceptional opportunity; an opportunity for human-centred developments, including improvement ofwornen's status in health; an opportunity for ushering in a new era of focus on human lifestyle and human behaviour as a key not only for AIDS control, but also for the future of man; an opportunity to link AIDS control strategy to the broader framework of health delivery services with a wide ranging impact on a variety of them, such as revamping of the sagging STD control programme, safe blood transfusion and streamlining infection control in hospitals; and, above all, an opportunity to counter discrimination and social ostracism against AIDS and to elevate human kind to new levels of feeling and consciousness." There are public health problems in addition to STDs which have a profound effect on AIDS. Nutritional deficiencies and tuberculosis among them have a close interr action with HIV/AIDS. Therefore, these should be tackled on a priority basis, using lessons learnt from the global fight with AIDS. The most important message is to use appropriate measures targeted to groups needing intervention. In this context, what we have learnt from AIDS should be termed as 'spin-offs', that is, we should get secondary benefits by attempting control measures for other problems also (Box 7). It will be appropriate to conclude this story by quoting Gandhiji : "I am hard-hearted enough to let the sick die, if you can tell me how to prevent others from falling sick."

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And yet, as Ramalingaswamy stated : "Gandhiji had nursed with his bare hands the weeping sores of a patient, Purchori Shastri, who was suffering from lepromatous leprosy." This is the concept of prevention on the one hand and caring (for patients) on the other. This is the story of AIDS. It is telling us to take care so that all those who died of AIDS did not die in vain. Box 7 To remain free of AIDS, you need to understand it. This need may turn into a habit, encouraging one to seek information abut other commoner communicable diseases in India. This should lead to a greater participation by the people, particularly students, in public health programmes. We may call it a 'spin-off' from the global interest and impact of AIDS. Indeed, there may be other 'spin-offs' if only we put this general, global scare in a proper national perspective. •

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Open, frank communication about risky or safe sexual behaviour will go a long way in preventing not only AIDS, but also, other sexually transmitted diseases (STDa). Condoms, used to prevent AIDS from the potentially risky sexual behaviour, will also help the much needed family planning programme. Lessons learned from AIDS control and intervention strategies for those at AIDS high risk situation will help formulate programmes for family planning, nutrition intervention, T.B. control, etc. The fear of contracting AIDS through contaminated needles and syringes will help in reducing the much greater frequent transmission of agents like hepatitis B virus and pyogenic bacteria, if doctors and medical and public health authorities: —avoid the use of unnecessary injections/blood transfusions; —introduce autoclaves or pressure-cookers in hospitals and dispensaries; and —encourage production, usage and safe discard of disposable syringes and needles at an affordable price (Contd.)

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A stricter enforcement of screening of donors and of good manufacturing practices—as recommended by the WHO— in all commercial concerns engaged in the manufacture of blood products and blood-based diagnostic reagents will improve the overall safety of the products. Stopping the use of professional blood donors, many of whom sell their blood for their livelihood, will eliminate also the hazard of contracting viral hepatitis which is transmitted much more frequently as compared to AIDS. The correct type of communication targeted to the most appropriate group—young, healthy adults, particularly students—seeking voluntary blood donation may keep our blood supply healthy and freely flowing, thus eliminating the need for professional blood donors.

Epilogue I The Origin of AIDS : How Did HIV Evolve? [Professor of Biology (PB) in conversation with the author] PB:

Since the beginning, several suggestions are made that a disease very similar to AIDS had been described in the Ayurveda system of our traditional medicine. Woidd you agree with this? KP: I can neither agree nor disagree as I have no knowledge of Ayurveda. It seems quite possible but only as a conjecture. You see, AIDS constitutes a yariety of clinical signs and symptoms and has a wide range of the so-called AIDS-indicator diseases and also opportunistic infections and cancers. Hence, nothing definite could be said one way or another. PB: By signs you mean objective evidence that can be observed by a physician. I also know symptoms are various complaints—physical or mental—reported by the patient. What are opportunistic infections? KP: There are various micro-organisms that reside within our bddies without causing any harm as long as our natural defence mechanism and immune system function normally. They start causing diseases only when our defence is down. They are called opportunistic infections. In the old days, diagnostic technology to recognize various opportunistic or other infections was non-existent. In these circumstances, it would indeed be difficult even for an expert in Ayurveda to assess

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whether AIDS or a very similar disease was truly described in the Ayurveda. What diagnostic technology were you referring to and based on that, how old would you consider AIDS? First, the question of technology. I presume you are not yet talking of the virus but only of AIDS. Recently, the Centre for Disease Control and Prevention (CDC) has added a new dimension to the definition of AIDS, viz. an accurate counting of a particular cell type—CD4 positive helper T cell. If these cells are less than 200/cu mm 14 in an individual, then he/she is considered to be a patient with AIDS. In countries like India, even now, it is difficult to fulfil this criterion because this particular technology is very expensive, and other methods are much less accurate. Even in industrialized countries including USA, this definition is not always applied to find out cases of AIDS. In these circumstances, specific tests for HIV are performed. Then I re-frame my question to apply to the earliest cases of HIV caused AIDS, what you may call HIV/AIDS. There are two commonly applied technologies. The first is serological testing using ELISA, Western blot or some other assays which could be performed on sera/plasma collected long time ago but which were stored under proper conditions. The other is a newer technology called the polymerase chain reaction (PCR) that first amplifies and then detects nucleic acid components specific for certain HIV genes. Using this technique, the presence of the virus could be determined in tissues or sections stored over long periods. Now to answer your question regarding the earliest cases of AIDS. Retrospective investigations have been carried out on stored sera and other material which were collected from different countries. Mind

Cubic millimetre.

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you, these were collected for an entirely different purpose; but if available in good quantity and quality they yield very useful information. For example, in sera from Africa—collected to study viral haemorrhagic fevers at the CDC—a sample taken in 1959 from Zaire contained HIV-1 antibodies. AIDS was also suspected in a seaman and his family from Norway in 1960s who died in 1976. Therefore, the earliest case was still considered to be from Africa, until 1990, when the information about a seaman from Manchester, England was published. This patient had died in 1959 with an unexplained immunodeficiency and with some typical opportunistic infections. He was confirmed to have suffered from HIV/AIDS as determined by the PCR technique. There was no evidence that this man had been to Africa. Thus, it would seem that AIDS as we recognize it now might have occurred in Africa and also in Europe around the same time. Based on this scanty information, one may assume that AIDS could have started in the 40s. Of course, we cannot categorically say there were no cases of AIDS earlier because they might have occurred in a scattered way here and there—what we call sporadic cases and therefore, might have gone unrecognized. PB: Okay. Let's turn to the virus now. Tell us something about how and where the virus could have originated. In other words, how did HIV start causing this disease called AIDS? KP: This may seem like 'fools rushing in where angels fear to tread'. But then, I will be in exalted company as several eminent scientists have preceded me. In fact, there had been raging controversies; allegations were made about racism on the one hand, and biological warfare on the other. Remember, those were the Cold War days before glasnost. A former Astronomer Royal postulated that the virus came from outer

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space. There had also been a suggestion about the alleged used in some African countries of monkey blood for sexual stimulation. The male blood for males and the female monkey blood for females, inoculated directly in the pubic area, in the thighs and back was supposed to have transmitted the monkey virus. So, I can also take up your challenge. First of all, something about these viruses which belong to the family of retroviruses. In Table 6 are mentioned related viruses called lenti or slow viruses; so called because they take a long time before they manifest themselves as a clinical entity. An important characteristic of Antiviruses has been their species specificity; this means that the cat virus is likely to cause disease only in cats and the sheep and horse viruses only in sheep and horses respectively. An interesting exception is the simian or monkey virus (SIV) which seems to be able to infect men also. PB: Do you mean to say we can get viruses from monkeys? KP: There is nothing new in that. As you know, we can get rabies virus from dogs, cats and even monkeys. Similarly some herpes viruses from monkeys can also infect us. These are just a few examples; the unusual part is that these lentiviruses can cross the species barrier. I personally feel this crossing over might not be as uncommon as is thought at present. HIV should be further divided into at least two broad serotypes and, as we shall see later, in still further groupings. HIV-1 is the virus most frequently encountered and causes epidemics all over the world (called pandemic) whilst, HIV-2 is found mainly in West Africa and to a much less extent in some other countries. Incidentally, in India, serological evidence for HIV-2 has been provided in the western and in southern regions although the virus has not yet been isolated.

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A unique property of all retroviruses is the possession of an enzyme which is called reverse transcriptase (RT). It helps these ribonucleic acid (RNA) containing viruses to make DNA (Appendix 1). Generally, a regular copying of DNA into DNA occurs, but when RNA directed DNA synthesis takes place, it leads to several mistakes which often go uncorrected. Hence, mutation (genetic alterations) occur in retroviruses in a 'fast-forward' mode. 15 Not only viruses collected from different areas or at different times show variation, even the strains from the same individual may also exhibit genetic variation (e.g. the isolate from blood and brain). Therefore, specialized genetic studies are carried out to differentiate viral isolates. Anyway, among the various immunodeficiency viruses there seems to be a closer relationship between the SIVs and the HIV; this is particularly so for HIV-2 which as a rule is closer to monkey viruses than to HIV-1. PB: I know that we evolved from simians, especially from apes. Did HIV also evolve from some simian virus? KP: Interestingly, there is supportive evidence that simian immunodeficiency virus(es) or SIV could get into humans. There is a record of a laboratory worker who poked his finger with a needle while working with a simian immunodeficiency virus and developed antibodies to the virus. There seems to be no further information and possibly the simian virus did not persist. On the other hand, there is evidence of isolation from a Liberian agricultural worker of an HIV-2 virus which is much more closely related to SIV, than to other HIV-2 strains. Simian viruses have been obtained from captive monkeys used for laboratory experiments and 13

'Viral Quasispecies', by Dr Manfred Eigen, is recommended as further reading, Scientific American, p. 32-39, July, 1993.

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also from feral (wild-caught) monkeys. Of special interest to us in India was the isolation from a rhesus (Macaca mulatto) called SIV M A C Later, however, no antibodies could be detected in wild-caught monkeys and it was considered that these animals might have got infected from some other monkeys kept in the cage. It was thought that the virus might have been transmitted from sooty mangabeys since this species is found to be infected in the wild. How do you think that could have happened; not sexually? I guess it could have occurred during some fighting among these captive monkeys. They might have scratched and drawn blood or some accident leading to bleeding might have occurred. Anyway, African green monkeys (AGM) captured in Kenya and Ethiopia had also yielded a retrovirus termed SIV AGM . These monkeys and also wild mandrills from Gabon showed no illness themselves but did carry the virus in the wild also. Incidentally, this is the kind of relationship viruses must like the best as they can survive at least as long as the infected animals live. The longer they live, the better for the virus. In contrast, the Asian monkeys (macaques) seem to suffer from an illness similar to AIDS in humans. Consequently they provide a very useful experimental animal model for HIV/AIDS (Advances in Immunology 52:425-474, 1992). Was there any repercussion of this monkey finding? Yes; with the recognition that the African green monkeys are (potential) virus carriers there emerged a hypothesis connecting the origin of HIV/AIDS with the use of polio vaccine. This vaccine for polio viruses had been derived from the primary kidney cultures of AGMs. The hypothesis seems plausible and also received some support. However, the argument against this hypothesis—polio virus vaccine being

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contaminated with some SIV retrovirus—is that hundreds of millions of people (mostly children) vaccinated throughout the world have remained free from AIDS. An alternative suggestion was made about the possible use of live polio virus vaccine by adult male homosexuals in much larger doses than routinely used. Supposedly in 1974, a doctor in the US had suggested it might give protection against recurrent herpes virus infection commonly affecting the 'gay' males. This was also strongly refuted later. Among all the monkey business, I personally find the virus(es) from sooty mangabeys SIV S M to be a potential ancestral candidate, at least for HIV-2. Quite a handsome looking animal (Fig. 25) which may partly be the reason why some people keep these as pets. The sooty mangabeys live in the coastal forest

Fig. 25 : A sooty mangabey.

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belt of West Africa, the areas where HIV-2 is also prevalent. If you are interested in all this monkey business, you should read Myra McClure's article (New Scientist 126:54-57,1990). Unlike the rhesus virus, the sooty mangabey virus (SIV SM ) seems to infect the animals in nature although both the virus and the host seem to live in some harmony. Wild mandrills from Gabon were also found to be infected with the virus called SIV M N D . From the phylogenetic tree, some workers have considered this virus as a possible ancestor of SIV and HIV. PB: What about HIV-1? Have they found any close relative among all the monkey viruses? KP: Well, if you're asking about the missing link for HIV1, no such link has yet been established for HIV-1 from monkeys, whether from Asia or Africa. But, among the African apes, the closest to the missing link has been a virus isolated from a chimpanzee called SIV C P Z . Two wild-born chimps, again from Gabon in central Africa, very near Cameroon, were found to be positive for antibodies to HIV-1; the chimp virus was isolated from one of them. The question still remains whether this one could possibly be an ancestor of HIV-1 or whether both the viruses might have evolved separately but in parallel without crossing the species barrier. As it often happens, no sooner was the chimp connection revealed that some scientists forwarded a suggestion: that the virus and thus AIDS might have entered the human population via direct inoculation of blood containing a malaria parasite from infected chimpanzees (and also, some sooty mangabeys) into human prisoner volunteers. Supposing one of these animals harboured a retrovirus similar to HIV-1 (chimp SIV CPZ ) or HIV-2 (sooty mangabey SIV), it might be the seeding of what we now know as

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HIV causing AIDS in human. In an interesting presentation, Charles Gilks proposed this hypothesis. He traced the experiments carried out in 1939 and also in 1954-55. A reply was given which states that such blood was used only in attempting mosquito transmission studies and not for human inoculation. This hypothesis seems quite possible to me. Why would you totally disregard it? Such a hypothesis could linger only as an interesting possibility. The time lapse of 40 to 50 years also seems right but it would be difficult to obtain any evidence one way or the other. Come to think of it, almost any hypothesis, however convincing it may appear, will probably remain untested and therefore, unconfirmed. Having said that, let us rush, and take a leap in the past and examine what could have happened. After all, research on how a virus could have originated and how the seemingly new disease syndrome emerged on the global scene might help in understanding other such emerging public health problems. Indeed, AIDS is a disease of civilization, resulting from certain changes in human behavioural patterns. Who knows other pathogens could also show up through large-scale changes in lifestyles of people. It does not necessarily have to be a sexually transmitted disease, you know. Yes, I understand. I have also read something on the origin of AIDS. Apparently, it was not only an evolution of a virus into the one with a difference, but also, a change in human behaviour that precipitated the AIDS pandemic. True, indeed! In the ultimate analysis, human behavioural factors might have ignited a slow smouldering into a raging fire. Rapid urbanization, breakdown of old family systems and values, sexual promiscuity, emancipation of gays (no more fear of the law at least in the Western world), rapid air and

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other modes of travel, massive use of blood transfusions (especially in African countries), unscrupulous trade in blood/blood products, and selling of organs, indulgence in self-injectable psychedelic drugs— all must have participated in fanning the fire. At the same time, the virus must have been good and ready to spread into humans. The combination of these events demonstrated how lethal this tiny bit of RNA, wrapped up in a rapidly changing coat (envelope) has turned out to be! There are two hypotheses generally forwarded to explain the origin of the virus of AIDS. The most favoured one is based on cross-species transmission from non-human primates. We already discussed that this is a possibility as SIV seems to infect humans. Studies on genetic relatedness and/or scrutiny of phylogenetic trees using computer analysis also confirm the possibility of such a transmission. Mind.you, this sort of transmission could be a rare phenomenon : in fact, it might have occurred at one point of time. That is to say that the chimp virus evolving into HIV-1 and the SIV from sooty mangabeys or mandrills into HIV-2, could have been a single-time affair. The other possibility considered is that the virus might have been pre-existent in humans. But, it might have had an extremely low prevalence or low virulence or both. Even if it caused AIDS, it might have occurred sporadically, i.e. scattered here and there or even in some isolated populations. So now, you have the two possibilities; which one do you prefer? PB: Both are attractive and also seem possible. What do the virological sleuths say about this? What about you? Have you exercised those grey cells of yours to unravel the mystery? KP: I agree with you that either could be possible. But,

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I would like to combine these two to explain how HIVs could have originated. Not a compromise, I hope. No, but something different, and original. Sprout away! As you yourself said, these hypotheses are unlikely ever to get tested and therefore, anything goes as long as we have some fun also. I negative that. After all, a hypothesis is to be based on a solid foundation of scientific facts. It should also explain all that has happened earlier and/or presented scientifically and should not be contrary to any established features and facts. If you agree, I will go ahead. So far, almost all studies seem to have been made on HIV strains (both HIV-1 and HIV-2) and the simian strains which are complete viruses. This means they have almost the full complement of the different genes. Of course, various isolates may show varying divergence in one or more of these genes. Based on such studies, Dr Gerald Myers, the famous figure behind the sequencing data-base project at Los Alamos National Laboratory (USA) has recognized at least five distinct families. Myers and associates have apparently formulated a geneological tree based on the core (gag) and envelope (env) genes to show close relatives. I have not read this paper but had only came across a report about it in Science (256:966, 1992). According to this report, the following five groupings were made of HIV-1 16 : • Viral strains from the the US and Europe • Brazilian and Zairian strains • Zambian 17 and Somalian strains • Taiwanese strains and • Strains from Uganda, the Ivory Coast and Kenya. Steve Sternberg, who

Various groups are labelled as A, B, C, etc. HIV-1 strains from Bombay (three isolates) and Goa (one isolate) were found to form a cluster with these and the South African strain.

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Map 1 SUB-SAHARAN AFRICA Mauritania

Sudan

Sierra Leone' Guinea Bissau

Liberia

Ivory Coast

Ethiopia

Nigeria Cameroon"

African

Namibia .(S.W. Africa)

Mozambique Botswana

South Africa

wrote the report, stated that Myers found HIV isolates from Gabon to fit into all the five groups and thus suggested that Gabon could be considered as the epicentre or the source of AIDS in the world. Sternberg then emphasized—almost mischievously— this particular issue and thus rekindled and played up the old accusations of racism. He also questioned the finding on epidemiological grounds since Gabon, an equatorial country on the Atlantic coast of Africa, would seem an unlikely place for the epidemic to have started. "It has one of the lowest AIDS infection rates among African nations with about 1.8 per cent of its 1.2 million population infected with the virus. It is bordered on the north by Guinea and Cameroon with

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Map 2 WEST AFRICA (SUB-SAHARAN)

infection rates of less than 5 per cent. But to the east, Gabon is bordered by the Congo, which has an infection rate of 7.9 per cent," he stated (see maps). PB: I know well what mischief such reporting can create. This is what I call mixing science with politics. Unfortunately, it happens all the time. KP: Well, Dr Myers wrote a letter refuting some of it. He concluded : "Where AIDS arose, as distinct from when and how, is irrelevant to medical science and should not

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Map 3 CENTRAL AFRICA (SUB-SAHARAN)

bring any criticism to any country," (Science 256:1502, 1992). But I am still going to bring in this where, strictly, on a scientific basis. The where could then explain the how part. Interestingly, highly divergent isolates of HIV-1 and HIV-2 seem to have been recorded mainly from these low prevalence countries in the west and the central Africa. This is the map of Sub-Saharan Africa (Map 1); this second map (Map 2) shows the countries in West Africa. Gabon is in central Africa, and slightly north is Cameroon (Map 3). Perhaps, now it will be easier to follow the isolation pattern of the highly divergent, and less infectious strains of HIV-1 and HIV-2. Remember, we spoke of Liberia in West Africa from where an isolate, much closer to SIV SM (i.e. sooty mangabey) was isolated. The authors concluded by emphasizing the need to target viruses from wild monkeys,

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and humans living in remote areas of Africa in a search for the origins of HIVs, and events leading to the recent epidemic spread of AIDS. Take Ghana, also in West Africa; yet another HIV-2 called HIV-2 ALT (for old) was reported from Ghana. This strain is so divergent that it stands out separately. The authors tend to believe the second hypothesis that the disease and the virus(es) are 'an old invention' of nature and, the crossing over to the pandemic state may be due to an association of social facts, technico-medical upheavals and viral variations. Naturally, their emphasis is on the virus isolated by them, the HIV-2 ALT. Coming to central Africa, where HIV-1 seems to be prevalent, divergent though complete human viruses resembling HIV-1 are those reported from Cameroon. The first one is called HIV1, ANT-70; it is found to be closer to the chimpanzee virus rather than to other human strains of HIV-1. Strange but an interesting feature of this virus strain is that it may also have some overlap with SIV from Gabon mandrill. Furthermore, antigenic evidence of the presence of ANT-70 like virus has been' recorded not only in Cameroon but also in Gabon. The other Cameroonian virus (MVP-5180) is very recently reported and has created quite a ripple among those responsible for blood transfusion services. You see, it is so very divergent that antibodies to the virus (called HIV-1 subtype 0) could be missed by the routinely used serological tests. PB: Anyway, so far, you have only shown that either the monkey-man or man alone hypothesis could explain the origin. Then why invoke a combination hypothesis? KP: True that either phenomenon could and might have occurred some 50 or more years ago. But should we not trace it to when it could have really begun? PB: Okay, so let's go as far back as possible in the evolutionary history.

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KP: That's what I intend to do. In fact, just recently, a report has been published which traces the possible evolution of retroviruses. Remember we spoke of RT— reverse transcriptase with a unique role? This new finding suggests a plasmid for RT, Oh, I know, a plasmid is a free moving closed circular DNA with some genes which may benefit these microorganisms. So, they found the RT progenitor in the genetic material of—you will never guess this—a fungus! This fungus grows on decayed vegetation. The missing link entities were found in the mitochondria which produce the energy of the cell. In their turn, mitochondria are believed to have evolved from some ancient bacteria. This is reported to have occurred a billion years ago. Gradually, these elements could have evolved into retroelements or what are called retrotransposons. These are endogenous elements that remain totally hidden (integrated) within cells. They could also be passed to the offspring hereditarily. Humans are known to harbour such silent particles that could remain dormant over centuries. PB: Could these he like the so-called IAPs you often talk and have written about it also in Ch. 5? KP: Do I sense some sarcasm in your tone? Never mind; when we first reported isolation of an IAP-like agent from a pregnant woman from southern India (presented in IVth International Conference on AIDS, Stockholm, Abstract No. 1132, p. 145, 1988) only mouse, other rodents and some monkey IAPs were recognized. Later, however, two more reports of human intracisternal A particles have been published. Indeed, IAPs have been considered to be a family of retrotransposons. But, let me not start on this topic now as I might go on and on . . . Consider some human population(s) harbouring such retro-elements. They might be living scattered

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at different places and not necessarily in Africa. Maybe, centuries go by before such elements finally encounter some exogenous [from outside] virus(es). For example, say chimpanzee virus. Initially, nothing happens, but gradually these IAPs acquire some required genetic material from this exogenous chimp virus. Now, a recombinant of a virus with envelope and the full complement of regulatory genes emerges; in fact, the first emergence of HIV-1. A similar event but with another simian virus, say sooty mangabey or a mandrill and you have HIV-2. PB: Now I see the African connection because of African monkeys and apes. But why consider the countries with low prevalence like Gabon or Cameroon? Makes no sense to me. KP: Mind you, I can build a hypothesis only on what I know of the available information. It is likely that I might be unaware of several publications relevant to the subject. Recently, aberrant HIV-1 strains have been isolated from Cameroon as we saw earlier. Refresh you mind by taking another peep at the map. Gabon and Cameroon are neighbours (Map 1). There was also antigenic evidence of the presence of at least one aberrant strain in Gabon. Thus, aberrant but complete HIV-l-like virus(es) have been circulating in these countries, perhaps, without causing much of the disease AIDS. Coming to Gabon, evidence was provided in 1989 of a highly defective HIV-1 strain isolated from a healthy Gabonese pregnant woman. Not only in this woman, but in several others, atypical serological pattern was observed in Western blot tests. Antibodies only to the p24/p25 Gag protein were detected. This type of result is generally disregarded as negative, or, considered as indeterminate. Because they were not uncommon in Gabon, the authors had set their aim on isolation of an incomplete type of HIV-1. Perhaps, the presence

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of such virus-like particles might in fact be protecting those persons harbouring them and hence, the low prevalence of AIDS ; who knows? Such incomplete or defective virus(es) could be just one step behind the evolution to the aberrant though complete HIV types. Defective particles might be circulating in Cameroonian population also. Thus, till the time something new gets published, I opt for Gabon and/or neighbours like Cameroon where it could actually have begun. HIV-2 also could have originated from these areas (neighbouring West Africa), although in this case, a recombinant might emerge with a virus such as the one from sooty mangabeys or wild mandrills. Incidentally, HIV-2 is not only much less pathogenic, it is also shown to be spreading much slower. So there you have my hypothesis! PB: Indeed, quod erat demonstrandum or, Q.E.D. KP: Not quite, my friend, there is no proof. But, you must admit I did use my grey cells.

Epilogue II Demystification of a Dozen Myths, Misconceptions and Teasers "Falsehood flies and truth comes limping after; so that when men come to be undeceived, it is too late; the jest is over and the tale has had its effect." —Jonathan Swift (1667-1745) Myths 1. AIDS affects only foreigners (later modified) and, prostitutes, gays and those who abuse drugs by injecting themselves. Ans. There have now been 728 patients of AIDS officially recorded in India while the number of foreigners with AIDS remains in the twenties. In fact, NACO no longer reports AIDS in foreigners separately. While it is true that prostitutes, gays and intravenous drug abusers may be more vulnerable to HIV infection, they are not the only ones to be infected. This myth was blown to pieces in 1988 itself as can be seen from the following: This is the story of the very first well-known indigenous case, a school teacher in Tamil Nadu. He was given transfusion of blood at a hospital in Vellore (Tamil Nadu) for excessive haematemesis. His immune mechanism was probably depressed because of treatment with certain drugs, and he soon became very ill and was admitted to a hospital in Madras. On suspicion, his blood was tested for 18

Vomiting of blood due to haemorrhage of gastric ulcers.

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AIDS virus infection and he was found to be confirmed seropositive. He died but not before undergoing indignities and discriminatory Press publicity. This led to retrospective tracing of the donor whose blood was given to this patient. The donor turned out to be be a young Indian male who was not a paid or a professional donor. He had donated blood for his wife who was admitted to this hospital for delivery. However, the wife did not require blood and so later, it was given to the school teacher. The donor had no history of exposure to the virus abroad. Inquiries revealed him to be a promiscuous heterosexual; he was found to be seropositive for AIDS virus infection when tested later. His wife and the young child also tested positive. Later, the man committed suicide. Epidemiological features of this case vividly demonstrate the three major modes of transmission of AIDS: • First and the most important is the sexual transmission. The blood donor, who had heterosexual, unprotected intercourse with multiple partners had got infected sexually, probably through contact with some infected prostitutes in Tamil Nadu. He had not yet developed symptoms but had passed on the infection to his wife, also through sexual contact. • Second is transmission through blood and/or blood products, or, through contaminated unsterilized needles and syringes. The heterosexual male was accepted as a 'replacement' donor and his blood was transfused to the patient who really needed blood. However, since the recipient was immunosuppressed, he was highly susceptible. His vulnerability resulted in his getting AIDS and succumbing to it more rapidly than the donor and his family. • Third is perinatal transmission, i.e. from mother to her offspring. The wife of the 'promiscuous' heterosexual male became pregnant and unknowingly infected her child. Where did the infected prostitutes pick up their virus infection? Practically no contact tracing has been

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attempted, but an intelligent guess would be a long chain of sexual transmission beginning some time in the early 1980s. There is no information whether the prostitutes used injectable drugs as in some other countries. However, another possible (interlinked) mode of transmission could be through contaminated, unsterilized or improperly sterilized needles and syringes which might have been used for medical injections given to them in STD clinics. The fact is that tragedy struck two families but it was found out too late! At least now, we can learn how to prevent AIDS from this story which is full of 'if s'. • The donor might have remained free of AIDS infection if he were not having sex with multiple partners. He should have had sex only with his wife in a healthy and a safe way. • The wife might not have been infected if the husband had consistently and correctly used a fresh condom every time he had sex with his wife or with other partners. • The child would have escaped the sword hanging over his head if the mother was not infected. • The infected blood would not have been accepted if the concerned blood bank in the hospital had established routine screening for HIV infection. • Perhaps, the school teacher might have had a longer life if he were not immunosuppressed and hence highly vulnerable. The school teacher had indeed been a teacher even in death. His most important lesson to us is AIDS IS PREVENTABLE IF WE MODIFY OUR BEHAVIOUR. 2. If AIDS is transmitted through blood, why not through mosquito bites? Ans. This doubt seems to disturb many people while others, who are not exposed to mosquitoes feel rather complacent. Why mosquitoes do not act as 'flying needles' transmitting the virus has already been explained in Ch. 2. A

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comment made by Dr Jonathan Mann, who was the Director of the Global Programme on AIDS (GPA) of WHO in 1987 is revealing : "It would be a tragedy, would it not if people started putting up mosquito netting, in order to prevent infection, instead of using condoms. It is not the putting up of the mosquito netting but what you do under the mosquito netting that counts." No doubt you may prevent getting malaria by using mosquito nets but not AIDS. 3. AIDS means death, and if any type of sexual intercourse leads to AIDS then, 'sex' also means death. Ans. Sooner or later, patients with AIDS die and so the first part is true. But the second part is not, because HIV, the virus of AIDS could be contracted only if a partner is infected with the virus. In Fig. 21 (Ch. 9) are presented several alternatives for safer 19 sex including abstinence or avoidance of premarital sex. Indeed, a strictly monogamous sexual relationship between two faithful and uninfected partners is safe as long as both have not had sex with others in the past and continue to remain faithful. Such a relationship is hazard-free penetrative sex whether it is heterosexual or homosexual; vaginal, oral or rectal. Risk is involved in having penetrative sex with an infected partner; the question is if sex is enjoyed with multiple partners [whether with commercial sex workers (CSW) or others] how to ensure they are all free of HIV infection? A more practical alternative is to use a condom 20 consistently, and correctly, whether your partner is a CSW or a friend. Of course, where there is life, there is an element of risk (Box 8); but why take undue risks? We teach our 19

20

'Safer' is used instead of safe to indicate that measures recommended may nof be foolproof. The idea is to be as safe as possible and 'safer' Uian with practices followed in the pre-AIDS era. For correct usage of condoms, read CARC Calling 3(4) : 16, 1990, 4(4) : 21, 1991, 6(4) : 10,36, 1993 and 7(2) : 1994.

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Box 8 Risks To laugh is to risk appearing the fool; to weep is to risk appearing sentimental; To reach out for another is to risk involvement; To expose feelings is to risk exposing your true self; To place your ideas, your dreams before the crowds is to risk loss; To love is to risk not being loved in return. To live is to risk dying. To hope is to risk despair; to try at all is to risk failure. But risk we must. Because the greatest hazard to life is to risk nothing: The man who risks nothing does nothing . . . has nothing . . . is nothing . . . He may avoid suffering . . . but he simply cannot learn, feel, change, grow, love or live. Chained by his certitudes, he is a slave. He has forfeited freedom. Only the person who risks can be called A FREE MAN. Anon

children how to cross streets to protect themselves from traffic accidents; also, to avoid strangers, etc. Should we not teach them about protective sex also? After all, safer sex is smarter sex. 4. Sex education for the young is not good as it encourages them to indulge in early or increased sexual activity. Ans. This is not true as has been shown by a review made by the WHO Global Programme on AIDS of studies on the effects of sex education in schools. Some 35 studies were included and the conclusion from the majority was that the education imparted, showed neither an increase nor decrease in the levels of sexual activity. Ten studies showed an increase in the adoption of safer

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sexual practices in sexually active youth. In fact, Dr Prakash Kothari, Head of Sexual Medicine at the Seth G.S. Medical College and K.E.M. Hospital, Bombay strongly recommends that sex education should be started for adolescents which should also tackle the rampantly prevailing myths and misconceptions. 21 5. Masturbation is harmful. It leads to impotence, even insanity. Ans. Most sexologists and other experts strongly refute this. In fact, in post-AIDS era, masturbation has been recommended as one of the safest alternatives among non-penetrative sexual modes. Dr Kothari states: "Masturbation is beneficial as it trains the individual's neurological system to respond to various types of stimuli. It also provides a pleasurable safety valve or outlet for the release of sexual tension, thus reducing the incidence of sexual crimes, unwanted pregnancies and sexually transmitted diseases including AIDS." Misconceptions 6. We can get HIV and AIDS by donating blood. Ans. This is not at all true as long as blood is donated at blood banks which follow all standard safety procedures and good practices. Even then, we can assure ourselves that a new disposable or properly sterilized set of equipment is employed for collection. Remember that a good standard blood bank has the same noble motive as that of an unpaid altruistic blood donor: namely, blood should always be a life-saving fluid and not a forerunner of death either to the donor or the recipient. 7. Soap and water can kill HIV, the AIDS virus. Ans. Not true, because ordinary soap and water do not 21

Further reading: CARC Calling, 6(No. 4), p. 4, Oct.-Dec., 1993.

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kill the virus. However, washing hands with soap and water is indeed the first line of defence as it dilutes out or washes off the contaminant. In order to kill HIV as also the hepatitis virus, one needs to use chlorine releasing compounds such as bleaching powder or sodium hypochlorite. Blood-stained clothes of AIDS patients or blood spills on table tops, floors, etc. should be covered with 2 per cent solution for 30 minutes before they are cleaned (with soap and water) or wiped. [For details see chart in CARC Calling, 7(1), 1994]. 8. Condoms are not required for protection against AIDS if other contraceptive measures are followed. Ans. This is incorrect because among all contraceptive measures, condoms alone are protective against HIV and other infections. Therefore, while pregnancy is prevented with pills or intrauterine device (IUD), these measures are unable to protect against infection. The same is true with procedures like 'vasectomy' for males and 'tubectomy' for females which are important measures for pregnancy prevention although they fail to prevent HIV and other infections. 9. Circumcision in men is unhealthy as it removes a shield against irritants. Ans. On the contrary, uncircumcised men are at increased risk for a number of STDs (sexually transmitted diseases). Uncircumcised homosexual or heterosexual males have been shown to have a greater risk of HIV infection. As a matter of fact, a recommendation made by the Centres for Disease Control and Prevention of the USA is to put on the condom after pulling the foreskin back. The foreskin or the glans penis of uncircumcised men are thought to be more susceptible to trauma with development of micro abrasions during vaginal or rectal intercourse compared with that of circumcised man. Because of the folds of the skin in the glans penis the chance of harbouring

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any sexually transmitted organisms is greater in uncircumcised men. Therefore, penile hygiene including cleaning of the glans penis is an important aspect of preventing STDs in uncircumcised men. Teasers 10 . In the Third World countries, like India, breast-feeding by HIV-infected mothers is recommended whereas in most developed countries, it is discouraged. Ans. In Ch. 2 it was mentioned that there are chances that breast-milk can infect babies of HIV-infected mothers. This chance is substantial among women who become infected during the breast-feeding period but is lower among women infected before the time of delivery, especially if HIV infection has not progressed to AIDS. In the absence of this information, the chance of passing the HIV infection through mother's milk should always be considered. The experts who recommend breast-feeding are guided by a comparison of HIV transmission rates of breast-fed babies versus the risk to child survival by bottle-feeding. Breast-milk contains substances which protect the baby from many infections and also provides good nutrition. Contrast this with bottle-feeding. It may introduce harmful germs which may lead to many serious diseases. Babies will suffer from malnutrition and may die of gastroenteritis and dehydration. Therefore, when it is difficult or not possible to provide safe and nutritious top-feed, breastfeeding is strongly recommended. This depends on mother's knowledge to follow hygienic principles and the ability to afford good nutritious and safe substitutes for breastmilk. Essentially therefore, the recommendation considers levels of education and socio-economic status of HIVinfected mothers and not their geographic location such as the developed or the developing world.

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11. Confusion about HIV/AIDS spreading through razors in barber shops and hairdressing/beauty salons. Ans. Piercing instruments including razors, ear piercing, tattooing equipment may scratch or cut the skin and may lead to slight bleeding. Therefore, they pose a potential risk of transmitting blood-borne infections. Hepatitis B virus (HBV) has at least once been reported to be transmitted through sharing of razors. HBV is far more (40120 times) infectious than HIV. However small, there exists a potential risk of transmission of HIV through blood contaminated instruments like razors, scissors and clippers used by roadside barbers. This could occur because the same blade/instrument might be reused again and again without even washing, let aside sterilizing them. HIV may survive in dried blood for several days and hence, the possibility of transmission. In contrast, barber shops and salons, which follow hygienic practices of cleaning and sterilization would have eliminated even this small chance of transmission. Places of pilgrimage like Tirupati where a large number of people get their hair removed (sacrifice and for performance of last rites) also have great potential if blood-stained instruments (clipper, razor, etc.) are reused without sterilization. Obviously, some operational research is needed to determine appropriate intervention methodology to prevent such transmissions. 12. Voluntary testing for HIV is frequently advocated as if it is beneficial to those who volunteer for the same. Ans. Voluntary testing is not advocated for those who go abroad or those who are just curious. It is, however, recommended for those who suspect themselves to be at some risk due to a particular sexual lifestyle or situation (e.g. emergency blood transfusion or such). The person is (or should be) counselled whether found positive or negative.

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Naturally, a major part of the advice to HIV-infected persons concerns measures to prevent the spread of HIV to others. These include practising safer sex, never to donate blood, to avoid other infections, etc. All these measures are beneficial to the HIV-infected persons also in delaying the progression to AIDS. Wearing condoms consistently and correctly not only prevents HIV passage to partners but also reinfection of the already HIV-infected person. It is now known that among several factors helping progression of HIV disease to AIDS is the load (amount) of HIV within the body. Thus, avoiding a further dose of HIV (from unprotected, penetrative sex with infected partners) might be beneficial the same way as avoiding other infections and stress and having appropriately adequate nutrition. In other words, AIDS should be treated as a chronic disease like diabetes. After ascertaining one's diabetic status, the attempt is to learn to live with it by following several do's and don'ts. The same principle applies to HIV in order to meet the challenge of AIDS.

The Challenge of AIDS is written to impart knowledge about AIDS and a realisation of the challenge that the human immunodeficiency virus (HIV) poses to us. The book briefly covers different aspects ranging from the origin of HIV and AIDS to the most recent developments in vaccine. AIDS research has attracted some of the finest brains among doctors and scientists of the world; and yet, an effective cure eludes us. Progress in vaccine development seems to take two steps forward, but one-and-a-half steps backward. In these circumstances, prevention is the only goal. The book provides the necessary knowledge, but it cannot supply the weapon to fight the challenge of HIV/ AIDS. Indeed, that weapon—a mind prepared to apply the knowledge—rests with the reader. 'i Dr Khorshed M. Pavri, former Director of the National Institute of Virology (NIV) at Pune, is involved with research on viral diseases and is a member of the WHO expert panel on viral diseases. Since 1986, she has been initiating studies on AIDS and HIV, including isolation of the virus. At present, she is working as the Project Director for the Bombay-based ICMR Centre for AIDS Research and Control (CARC). She is also the editor of the quarterly journal, CARC Calling. Dr Pavri has been active in AIDS prevention programmes undertaken by governmental and non-governmental organizations (NGOs) and is one of the founder-members of the Society for Prevention of AIDS (SPA) in Bombay.

NATIONAL BOOK TRUST, INDIA