A study of the use of tenofovir to prevent HIV infection in commercial sex workers has been stopped by the Cambodian government following protests from commercial sex workers.
The study, which was designed to randomise 960 commercial sex workers to take a low dose of tenofovir or a placebo for one year, was attacked at the Fifteenth International AIDS Conference by Cambodian activists who argued that the trial’s provisions for post-study care were inadequate and that prevention counselling was limited in order to increase the chance that infections would occur during the study.
The Cambodian Prime Minister Hun Sen said on August 3rd: "If a trial is needed, please do it on animals, and don't use Cambodians." In a further statement on August 11th Health Minister Nuth Sokhom said that the Prime Minister did not want the study to go ahead because the government was worried about the study’s effects on the human rights of Cambodian people.
No individuals have yet received tenofovir in the Cambodian study. The study is being funded by the US National Institute of Allergy and Infectious Diseases, the University of New South Wales, Australia, and the Bill and Melinda Gates Foundation. Gilead Sciences, manufacturer of tenofovir, is providing its product free of charge.
The study’s rejection by the Cambodian government could presage similar difficulties for large-scale studies in the future.
The dispute also raises questions about the standard of care that should be offered in studies in resource-limited settings.
ACT UP Paris, which was vocal in its criticisms of tenofovir pre-exposure prophylaxis studies during the Bangkok AIDS conference, charges that a very similar tenofovir study being conducted in Cameroon, Nigeria and Ghana is unethical, and that it exposes women to an unnecessary risk of infection. In particular they criticise the standard of HIV prevention counselling being offered within the trial, arguing that one doctor and five counsellors to 400 women is an unacceptably low ratio.
Ethicists have argued that vaccine trials should make the best possible efforts to avoid participants from becoming infected by ensuring that people receive proper counselling on HIV prevention, treatment for sexually transmitted infections and provision of condoms.
The US National Institutes of Allergy and Infectious Diseases argues that participants will benefit from regular exposure to HIV prevention messages and free condoms at their monthly clinic visits, as well as free testing for HIV and hepatitis and free treatment for sexually transmitted infections.
The International AIDS Vaccine Initiative has proposed that five years of antiretroviral treatment should be provided for participants in vaccine trials who become infected, although no international agreement has been reached.
The International AIDS Society recently agreed guidelines with pharmaceutical companies carrying out treatment studies in resource-limited settings that would ensure a minimum of two years treatment according to WHO guidelines.
Participants in the Cambodian study will be referred to the Cambodian National Center for HIV, AIDS, Dermatology and STDs in Phnom Penh if they contract HIV during the study. NIAID could not provide information on the standard of care available to participants who seroconvert, despite repeated requests over 48 hours from aidsmap.com.
Long-term health care to monitor for side effects
Cambodian women also called for a commitment to provide monitoring and treatment for any long-term side effects of the treatment - in effect, health check-ups for the rest of their lives.
Commenting on the Cambodian demand this week, a spokesperson for the National Institute of Allergy and Infectious Diseases, pointed out that offering long-term care over and above what is available to the rest of the community “would constitute an unreasonable inducement to participate and could be considered coercive and unethical.”
Tenofovir has not been tested as monotherapy in HIV-negative individuals before, and extrapolation from any study in HIV-positive individuals is unsafe due to the use of the drug in combination with other antiretroviral agents in HIV-positive people. The only guidance comes from studies in rhesus macaques, which found limited evidence of reduced bone mass and lower body weight in monkeys exposed to the drug in the womb. Reduced bone mass is a theoretical concern in adults too, but has yet to be proved or disproved by long-term studies.
Pregnant or breastfeeding women would not have been permitted to take part in the Cambodian study.