AIDS vaccine trials in India: Ethical questions

[Guest guest]

AIDS vaccine trials in India: Ethical questions

By Sandhya Srinivasan

The AIDS vaccine trials in India are one step closer to fruition.

Sandhya Srinivasan examines the ethical problems posed by such

trials, particularly in developing countries

On April 16, 2002, the National AIDS Control Organisation (NACO), the

International AIDS Vaccine Initiative (IAVI) and the Indian Council

of Medical Research (ICMR) announced that a year-old collaborative

project to develop an AIDS vaccine for use in India had advanced one

step closer to fruition.

Speakers at a meeting for the press indicated that vaccine

development was proceeding according to schedule; phase I clinical

trials were expected to start in 2003, and an advisory board set up

to address ethical issues concerning the AIDS vaccine trials had just

held its first meeting.

The project kicked off in March 2001 when the ICMR, IAVI and the US

biotechnology firm Therion Biologics signed an agreement to develop

an AIDS vaccine suitable for India. IAVI would fully fund Therion's

development of an AIDS vaccine specific to the HIV (subtype C) common

to India, and would 'accelerate' the process of getting this vaccine

into clinical trials. Therion would produce the vaccine in quantities

sufficient for phase I clinical trials, after which it would transfer

the technology to an Indian vaccine manufacturer which would produce

lots for further trials. If the vaccine cleared all trials, it would

be made available in India at a 'reasonable' cost.

The genetic material to develop the vaccine was collected by

researchers at the National AIDS Research Institute (NARI) in Pune,

cloned and sequenced and then taken to Therion for vaccine

construction.

What exactly is the HIV vaccine?

The preventive vaccine under development is described as a 'modified

vaccinia Ankara (MVA) vaccine'. Genetic material from six HIV genes

(env, pol, gag, rev, nef and tat) from an Indian isolate of subtype C

(accounting for 80 % of infections in India) is inserted in an MVA

viral 'vector' -- or transport mechanism for the HIV DNA. Scientists

say that vaccinia Ankara is a harmless version of a pox virus; it was

also the basis for smallpox vaccines. The vaccine is constructed from

pieces of HIV DNA, which cannot form a whole virus, and so there is

no risk that recipients of the vaccines could become infected with

HIV.

The idea is that when the immune system recognises the HIV genetic

material contained in the vaccine, it will stimulate the production

of cytotoxic T lymphocytes, specific immune cells that kill other

cells infected with HIV. Thus the preventive vaccine would prepare

the immune system to react fast if the person becomes infected with

HIV, and control the virus before it is able to take hold. This

approach is based partly on research to understand how it is that

some people don't get infected with HIV despite repeated exposure to

the virus; it was found that they had naturally high levels of these

HIV-specific 'killer cells', which presumably enable them to resist

infection.

Trials of HIV vaccines are being carried out world-wide, though it

will be many years before a vaccine will reach the market. IAVI-

sponsored research has produced two candidate vaccines currently

under trial in Africa. Glaxo Kline has a protein-based vaccine

poised to enter trials. The Phase III trial by the Bangkok Vaccine

Evaluation Group of VaxGen's gp120 vaccine, in a cohort of 2545

intravenous drug users, is ongoing.

Some activist groups have given a cautious welcome to the

announcement of an HIV vaccine for India. They raise three basic

questions: 1) Will all efficacy be maximised and risks minimised? 2)

Will the programme move carefully to ensure that vulnerable groups

are not exploited, and that human studies are appropriate, done with

fully informed and voluntary consent of participants, and do not harm

them physically or socially? 3) How will vaccine research and

development proceed effectively when preventive programmes are in

chaos, and drug treatment is a luxury for the very, very rich?

Partners of commercial sex workers and intravenous drug users -

people at high risk of getting infected with HIV -- have been

identified for the vaccine trials in Maharashtra, Tamil Nadu and the

North-East.

IAVI is a non-profit organisation founded in 1996 to help develop

preventive HIV vaccines for use throughout the world. According to

its website (www.iavi.org), its work is concentrated in four

areas: " creating global demand for AIDS vaccines through advocacy and

education; accelerating scientific progress; encouraging industrial

involvement in AIDS vaccine development; and assuring global access " .

IAVI's funders include USAID, the World Bank, UNAIDS and various

private foundations.

Boston, USA-based Therion Biologics Corporation is essentially in the

development of therapeutic vaccines for cancer, according to Mark

Chataway of IAVI. According to Therion's website, it is also

developing preventive AIDS vaccines in a programme supported entirely

by the United States National Institutes of Health. It has four such

candidate vaccines in development, one of which is in Phase I

clinical trials.

IAVI and the Indian government have committed themselves to ensuring

that AIDS vaccine clinical trials in India will be conduced with

community participation and adequate infrastructure, and after

addressing the ethical issues concerning clinical trials. The

government says the process will be transparent and it will ensure

that participants' consent is voluntary and informed. It says that

meetings planned with the various stakeholders are meant to solicit

their support to expedite vaccine research.

The April 16 announcement raises a number of issues that merit

informed public discussion. A few of them are mentioned below:

AIDS vaccine trials pose a number of ethical problems, particularly

in countries like India where a higher estimated incidence of HIV

(than for example in the US) permits smaller sample sizes and faster

results. They are conducted on groups whose vulnerability is the very

reason they are at higher risk of HIV.

These trials depend on healthy participants getting exposed to the

virus due to their behaviour; a significantly higher incidence of HIV

in the control group is needed to prove the vaccine's efficacy.

Researchers experience a conflict of interests: between this

technical requirement and their obligation to provide preventive

advice on safer sex and injecting practices, as well as condoms and

clean needles or bleach.

Researchers will also have to ensure that participants truly

understand that the experimental vaccine is not proven effective, and

they should presume that it offers no protection. Further,

participants will not know if they have received the experimental

vaccine or a placebo which offers no protection at all.

What will the standard of care be for participants who become sero-

positive during the AIDS vaccine trial? The Helsinki Declaration

requires that participants in a trial be provided the best known

prophylactic and therapeutic care. Will the government commit to

providing the highest possible standard of treatment - life-long

triple anti-retroviral therapy -- as available to research

participants in the developed world?

None of the vaccines under development are expected to have 100 per

cent efficacy. In fact, a vaccine of just 50 per cent efficacy may be

considered acceptable for a country with a high prevalence of HIV,

because of the number of infections it could reduce. Before trials

begin, we will need to know more about the estimated efficacy of the

vaccine currently poised for trials in India. Second, given the

controversies on HIV figures in India, we will need to know by what

calculation it was considered acceptable. Finally, how will the

programme ensure that vaccinated people truly understand the limits

of protection?

Ensuring availability: The NACO-ICMR-IAVI venture envisages that once

a vaccine is developed and clears Phase I clinical trials, Therion

would transfer the technology to an Indian pharmaceutical for further

production and trials. The licensed vaccine would be sold in this

region at 'manufacturing cost (excluding all development costs) plus

a small margin'. This may still be unaffordable to the majority of

people at risk of HIV. The programme needs to tell us exactly how it

will make any AIDS vaccine available to the poorest of the poor, who

would need it the most.

Drug trials in India: Informed consent is not taken

There is no comprehensive information on drug trials - or medical

research of any kind - in India. It is believed that most drug trials

are done in public hospitals, and on poor patients. Over-stretched

researchers in government hospitals are effectively bribed with the

offer of equipment like computers, and some stipends to pay for extra

staff, notes Dr Yash Lokhandwala, cardiologist at Hinduja Hospital,

Mumbai. Ethics committees are usually controlled by the hospital

dean, says Dr Sunil Pandya, neurosurgeon at Jaslok Hospital, Mumbai,

so when a project bringing in a lot of money is presented to the

ethics committee, it will get cleared. Informed consent is not taken;

most doctors believe - incorreclty -- it's just not possible to take

informed consent of the illiterate. It has been established that

patients in public hospitals when approached to participate in

research believe that if they refused, they would be denied the care

for which they came.

Government authorities such as the Indian Council for Medical

Research can control only the research that they fund. So when a

US 'entrepreneur' got to test out a vaccine for the Bovine

Immunodeficiency Virus (BIV) on people with HIV in Mumbai, through a

local support group, it was only when the patients' families filed a

criminal case that one of the doctors concerned (I H Gilada) was

arrested. At the same time, some ICMR institutions don't have

functioning ethics committees. Unfortunately, even those with

functioning ethics committees cannot guarantee that the committee has

screened the proposal properly, let alone monitored the research once

it starts.

http://infochangeindia.org/fetaures27.jsp

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