Unmet ethical concerns of the proposed preventive HIV vaccine trials in India

[Guest guest]

Indian Journal of Medical Ethics. Vol 1 303 July-September 2004

http://www.issuesinmedicalethics.org/

VIEWPOINT

Unmet ethical concerns of the proposed preventive

HIV vaccine trials in India

Joe

International Centre for Health Equity Inc, Melbourne, Australia. e-

mail: joe_thomas@...

According to estimates of the National AIDS Control Organisation,

there are 4.58 million people living with HIV/AIDS in India (1). An

effective vaccine is considered to be one of the strategies to deal

with the rapid spread of HIV infection in the country (2). I suggest

that an overemphasis on preventive HIV vaccine research in India

undermines the therapeutic HIV vaccine research needs and violates

the ethical principle of distributive justice. Further, the vaccine

campaign must address the vulnerability of potential trial

participants and limits of regulatory mechanisms.

The choice between preventive and therapeutic vaccine

Preventive HIV vaccines are designed to prevent HIV infection

whereas therapeutic HIV vaccines are designed to boost the immune

response of a person already infected with the virus (3).

The ethical dilemmas of promoting a preventive HIV vaccine over a

therapeutic vaccine in developing countries have been acknowledged

by some commentators (4). Leading proponents of distributive justice

advocate that members of society should have equal resources and the

power to use these resources (5). The selection of research

direction, emphasis of research, choice between preventive and

therapeutic vaccine are not value neutral decisions in the Indian

context. The distribution of public goods, including the products of

scientific discovery, is unequally structured on the lines of caste,

socioeconomic status, geographical location, sex and age.

The majority of people living with HIV infection in India are

unaware of their vulnerability and their HIV status. Many live in

grinding poverty and are deprived of the basic health care

facilities. The urgent needs of these people should take priority on

the research agenda. A preventive HIV vaccine may not bring dramatic

changes in the quality of life of these people.

The results of preliminary trials and other scientific data indicate

that commercial production and distribution of a preventive HIV

vaccine are several decades away (6). The continuing genetic

mutation of the virus could even make a universally effective HIV

vaccine an unrealistic expectation (7).

Some researchers have argued that a preventive vaccine represents

the best long-term hope for HIV/AIDS control (8). I suggest that

even if a universal HIV preventive vaccine becomes available, the

long-term hope for HIV/AIDS prevention is in political commitment,

in programmes that reduce the vulnerability of specific population

groups, and in addressing health inequities nationally and globally.

A biomedical solution will not provide an exclusive long-term

solution (9).

About 90% of HIV transmission among adults is through unprotected

sexual intercourse. Reduction in HIV transmission through sex is

possible through consistent and correct use of condoms. However,

vulnerability to HIV transmission and the ability to identify and

reduce are unequally distributed according to sex and socioeconomic

status (10). A programme for universal HIV prevention vaccination

will face similar obstacles.

HIV prevention strategies must also address structural factors

contributing to the vulnerability of women and marginalised

populations, and social support needs of people living with HIV

infection (11). This proposal may be weakened by unrealistic

expectations created by advocacy for an HIV preventive vaccine in

India.

In this context, one must carefully analyse the ethical implications

of investing only in a preventive HIV vaccine, and weigh the

opportunity costs of not investing in a therapeutic HIV vaccine.

Why therapeutic HIV vaccine research must take precedence in India

Therapeutic HIV vaccines offer greater opportunities to strengthen

the broader response to the epidemic and immediate benefits to

health care delivery systems. A therapeutic vaccine could contribute

to the reduction in burden of disease and enhancing the quality of

life of people living with HIV infection. Advocacy for preventive

vaccines must not compromise the need for a therapeutic HIV vaccine.

Due to the lack of data and experience in dealing with HIV therapy

in resource-poor settings, the Indian generic pharmaceutical

industry's capacity to provide cheaper anti-retroviral (ARV) drugs

is not fully exploited by health care providers. The current

standardised ARV therapy may soon run out of therapeutic options, as

they become less effective on large populations. An aggressive

therapeutic HIV vaccine research programme can offer alternative

solutions.

Testing on vulnerable populations

Careful considerations are to be made in testing an HIV vaccine on

vulnerable populations. It is necessary to ask questions about HIV

preventive vaccine research in developing countries: Are all

individuals equally capable of taking informed decisions

irrespective of their sociocultural context? Are individuals

entirely responsible for the consequences of their `informed

decisions'? Will clinical trial investigators ensure the best

interests of clinical trial participants?

The majority of participants in preventive vaccine trials are to be

recruited from vulnerable populations. They will have to take a

number of unquantified risks—the biological risk of getting infected

with HIV; unknown side- and long-term effects of the vaccine; unmet

treatment needs; social and economic consequences such as loss of

income; loss of existing insurance cover, incidental costs such as

travel, cost of seeking legal and medical advice, disturbance of

domestic life and potential stigma and discrimination.

We need to further discuss the conflict of interest between trial

volunteers who surely want to stay uninfected at all costs, and

researchers `needing' some people to become infected to prove that

those vaccinated are genuinely protected.

Need for data on behavioural and social issues

Discussion on the ethics of a preventive vaccine must be based on

information on people's beliefs about HIV illness and vaccine

efficacy; factors influencing willingness to participate in trials

and their understanding of technical concepts such as placebos and

the double blind methodology. There must be data on issues such as

the meaning of inducement in resource-poor settings; minimum

standards of informed consent processes, counselling procedures and

confidentiality requirements.

Regulatory framework

Commentators have noted that Indian regulatory agencies are weak and

medical councils refuse to act against errant doctors (12). The

Indian Council of Medical Research (ICMR), the key partner in the

Indian HIV vaccine consortium, has so far not been able to punish

those who violate its ethical guidelines. In the absence of a

comprehensive legal framework, how will ICMR demonstrate that it can

enforce its ethical guidelines?

In developed countries, Data and Safety Monitoring Boards are

committees of independent clinical research experts who review data

while a clinical trial is in progress and ensure that participants

are not exposed to undue risk. They are empowered to review data and

may also recommend that a trial be modified or stopped if there are

safety concerns, or if the trial's objectives have been achieved. Is

such close scrutiny possible in India?

Transparency

Investigators are obliged to make a statement on ethical issues

relating to their research and its resolution. There is no evidence

that members of the ethics committees of the vaccine trial have

rigorously analysed the ethical implications of the proposed trials.

In the absence of a detailed clinical trial protocol of the proposed

HIV vaccine trial in India, with details of risk and benefits— and

how they were assessed—the value of community consultations is

reduced to a public relations exercise.

Consultation on the HIV vaccine trial in India should be based on

a `white paper' on the risks and benefits of participating in the

trial and an in-depth debate on the priority and relative merit of a

preventive vaccine versus therapeutic vaccine.

References

1. Sharma S. The world vs. AIDS, 2004. India's growing AIDS

problem. World Press Review 2004;51.

Available from URL: http://www.worldpress.org/article_model.cfm?

article_id=1858 & dont=yes (accessed June 18, 2004).

2. Jayaraman KS. India targets local HIV strain in test of AIDS

vaccine. Nature 2004;427:185.

3. National Institutes of Health. Vaccine glossary, 2000.

Available from URL: http://www.niaid.nih.gov/factsheets/GLOSSARY.htm

(accessed on May 6, 2004).

4. Berkley S. Thorny issues in the ethics of AIDS vaccine

trials. Lancet 2003;362:992.

5. Sen AK. Inequality Reexamined. Oxford: Clarendon Press, 1992.

6. Esparaza J, Bhamarapravati N. Acclerating the development

and future availability of AIDS vaccines. Lancet 2000;355:206–6.

7. C. Policy issues in AIDS vaccine development.

2001.http://hivinsite.ucsf.edu/In Site.jsp?page=kb-08-01-11

(accessed on June 18, 2004).

8. Esparza J, Osmano S. HIV vaccines: a global perspective. WHO-

UNAIDS HIV vaccine Initiative. Geneva: WHO, 2003;183–93.

9. RP, Kalams S. The science of HIV vaccine

development.1998 http://hivinsite.ucsf.edu/nSite? page=kb-02-01-06

10.Loewenson R, Whiteside A. HIV/AIDS implications for poverty

reduction. UNDP Policy Paper, 2001.

11.Bloom DE, Sevilla J. HIV/AIDS and development in Asia and the

Pacific. A lengthening shadow. Asia Pacific Ministerial meeting,

Melbourne, Australia, 2001.

12.Mudur G. Use of antibiotic in contraceptive trial sparks

controversy. BMJ 2004;328:188.

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