From our UNC-Chapel Hill bureau, Stuart Rennie blogs:
Those attending the International AIDS Conference in Bangkok last July may fondly recall the destruction of the Gilead kiosk by members of the Asian Pacific Network of Sex Workers and ACT-UP Paris. Gilead posters were sprayed with fake blood, while passersby were playfully pelted by flying spoonfuls of symbolically red strawberry jam. The colorful and sticky protest was occasioned by Gilead Inc.s testing of its antiretroviral drug Viread as an HIV prevention method for sex workers in Cambodia, Ghana, Nigeria and Cameroon. Since last summer, the Gilead trials has become one of the hottest items in international research ethics.
Viread, or tenofovir, an FDA-approved drug, has been shown to boost immune responses and reduce viral loads in HIV-positive persons. The NIH, CDC and the Bill and Melinda Gates foundation are funding separate trials of Viread on human subjects to determine if the drug is safe and efficient for its use as a prevention pill to block acquisition of the HIV virus. The value of such a pill should be obvious: HIV transmission continues apace, particularly in developing countries, and there is no effective HIV vaccine in sight. Oral HIV prophylaxis would also benefit women, who often have difficulty negotiating condom use. A prevention trial of this nature, however, requires recruitment of study participants who are HIV-negative but at high risk of acquiring the virus. The CDC has funded ($3.5 million) trials in Atlanta and San Francisco among 400 men who have sex with men, scheduled to start this spring. The CDC is also running trials in the high HIV prevalence country of Botswana, and among HIV-negative injection drug users in Thailand. The Gates Foundation is supporting ($6.5. million) randomized, placebo-controlled trials of Viread with 2000 HIV-negative volunteers in Cambodia, Ghana, Cameroon, Nigeria and Malawi. The NIH awarded a $2.1 million grant to the University of California-San Francisco to test Viread on HIV-negative Cambodian women, mostly sex workers. Around the world, at risk HIV-negative persons (gay men, drug users, sex workers, Botswanans) are being recruited into HIV prevention studies on a drug marketed by a major pharmaceutical company and backed by powerful US donors and research institutions.
You dont need a PhD in bioethics from Case Western Reserve University to know an ethical minefield when you see one.
All ethical hands on deck: do the trial participants really know they are not being guaranteed immunity from getting HIV? Are participants given sufficient resources and education about the use of condoms and other preventative means? Are the women, even if educated about prevention, really in a position to negotiate condom use? And what will be provided to those who become HIV-infected during the trial? If weaving an acceptable path through these issues is not difficult enough, keep in mind that the participants are often from non-Western cultures where the understanding of biomedical research may be less than ideal. And note that from a strictly scientific point of view, it is in the researchers interest that (at least some) participants fail to take the recommended precautions and expose themselves to HIV transmission. The study design is an ethical tinderbox waiting for a flame.
Cambodia was the first to combust. Last August, the Cambodian trial of Viread was halted by the Minister of Health, citing safety concerns about the drug. But this was after pressure from the groups such as the Asian Pacific Network of Sex Workers, who were more concerned about compensation for sex workers becoming HIV-positive during the trial. And here is where the gloves came off.
In this corner, the sex workers union demanding 30 to 40 years of medical care for sex workers in the study who acquire HIV. In that corner, Mary Fanning, associate director of clinical research at NIAID, countering that offering such compensation would be tantamount to undue inducement, would invalidate voluntary informed consent, and hence would be, um, unethical. In this corner, ACT-UP Paris claiming that the $3 offered to prospective participants already constitutes unethical inducement, and calling for the immediate termination of Viread trials worldwide until participants were assured of effective HIV prevention education and resources, and received access to adequate treatment and care in event of HIV infection. In that corner, Ward Cates of Family Health International (the North Carolina-based non-profit health organization overseeing the Cambodia and Cameroon trials) arguing that the human rights of study participants were respected, because the care being offered to them was well above the standard of care in Cambodia. Any reasonable sex worker, it seems, would be better off joining the trial than plying her trade outside it (but isnt that, um, undue inducement?). However, opponents point out that we are talking about a country where the government spends $2 per person per year on health care (Asian Development Bank, 2004) and 23% of HIV-positive persons in need of antiretroviral treatment have access to it (WHO, 2005). Exceeding low standards, they argue, is nothing to write home about.
And now there is Cameroon . Anyone on a listserv about AIDS and Africa has been hearing fearful murmurings of unethical goings-on with the Viread trial in Douala, Cameroon for the past months. There was talk of consent forms in French and English for participants who knew neither; participants being told that they were all getting a sure prevention against HIV; no provisions whatsoever being made for those who became HIV positive. The subject line of one memorable post read: Scandal humanitaire au Cameroon!!! TEST FRAUDULENT DE SIDA CONTAMINATION AGGRAVEE, PAUVRES DE NOUS! On the 20th of January, members of ACT-UP Paris demonstrated in front of the Cameroon embassy in Paris, demanding the trial be stopped for reasons similar to those used against the Cambodian study. By the 4th of February, the Ministry of Public Health in Cameroon suspended the study. On state radio, Health Minister Urbain Olanguena Awono stated that his Ministrys audit revealed dysfunctions and certain measures need to be taken the by research team. He did not detail the dysfunctions, or list the measures, a move unlikely to slow down the rumor mills.
A preventive pill against HIV infection would be a powerful weapon in the fight against the AIDS pandemic, but the ethical challenges of designing and implementing a study proving its safety and effectiveness are daunting. But the quest for such a pill is not over. Look out for new installments of the Gilead saga in 2005.
[Stuart Rennie – guest post]