Johannesburg, South Africa, and Washington, D.C. -- Results announced yesterday from two clinical studies testing pre-exposure prophylaxis (PrEP) showed striking evidence that antiretrovirals -- the drugs used to treat HIV -- can also help prevent HIV when used by heterosexual men and women. In contrast to the effectiveness of PrEP demonstrated last year in men who have sex with men -- these studies provide the first proof that tenofovir disoproxil fumarate (TDF) and Truvada (TDF combined with emtricitabine) used daily can help to reduce HIV infection in heterosexual men and women.
The first of these studies, Partners PrEP sponsored by the University of Washington and funded by the Bill & Melinda Gates Foundation with drugs supplied by Gilead Sciences, enrolled 4,758 serodiscordant couples -- where one partner had HIV and the other did not. The independent Data Safety Monitoring Board (DSMB), in consideration of the findings from sites in Kenya and Uganda noted 62 percent fewer infections in those taking TDF and 73 percent reduction in participants randomised to Truvada, called for a discontinuation of the placebo arm. The protection levels of both drugs were considered to be comparable between men and women in the study and comparable between the two drugs. Good safety and tolerability were reported for both drugs, an important consideration when healthy uninfected individuals would be required to adhere to a daily medication. Importantly, as noted by the researchers, adherence reported in the study based on dispensed drug dosages was extremely high -- more than 97 percent.
In a different study, TDF2, sponsored by the US Centers for Disease and Control and Prevention (CDC) in Botswana enrolled 1,200 sexually active men and women to test the safety and effectiveness of Truvada as prevention. In October 2009, researchers had concluded that they may, in fact, not be able to show the effectiveness of Truvada as HIV prevention given that they were unable to retain the number of participants needed to show an effect. However, having made a concerted effort to bring back many of the participants who had been lost from the study, researchers were able to report efficacy findings in the final analysis. Similar to Partners PrEP, the study found a 62 percent risk reduction of HIV infection in the men and women who took Truvada compared to those in the placebo arm. This study also had high adherence at 84 percent as determined by the pill count.
"This is exactly what we've been waiting for," said Yasmin Halima, director of the Global Campaign for Microbicides, an international civil society organisation advocating for HIV prevention for women. "Highly vulnerable women -- especially those in poor countries have been waiting. Our job now as advocates, is to ensure that these exciting findings, along with other options such as vaginal microbicides, translate into practical options for women to protect themselves from HIV."
"What is thrilling," said Samukeliso Dube, head of Africa programs for the Global Campaign for Microbicides, "is that we are adding to the options available for women. For the first time, we have proof that both a pill and a microbicide work. Let's offer both to women. And let's do it now. We have lost too many women to the epidemic in Africa. We can't wait any longer."
In addition to the challenges of service delivery, the findings from these studies raise critical questions about continuing the use of placebos in ongoing studies testing the same drugs in women. The VOICE trial (Vaginal and Oral Interventions to Control the Epidemic) sponsored by the National Institute of Allergy and Infectious Diseases (NIAID), part of the US National Institutes of Health (NIH), is evaluating the safety and efficacy of TDF and Truvada as oral PrEP in women and uniquely, the study also includes evaluation of the daily use of tenofovir gel as a vaginal microbicide. Following the CAPRISA 004 findings last year that tenofovir gel used before and after sex could help reduce susceptibility to HIV, VOICE is testing the impact of the daily use of tenofovir as a microbicide. The study investigators announced that VOICE's independent DSMB is reviewing the data from these two studies in order to decide how to proceed with the trial.
"VOICE is exceptionally important. It is the only study that compares oral PrEP against vaginal microbicides. "VOICE could teach us not only what worked, but whether women expressed a preference for the oral pill or the vaginal gel," said Halima. The evidence is building that oral PrEP can help protect women from HIV -- begging the question, should we continue to include a placebo control in HIV biomedical prevention trials?"
The Global Campaign for Microbicides remains committed to making available a variety of tools that women in Africa can use to protect themselves from HIV, including microbicides, slow-release vaginal rings, in addition to other prevention options. Ease of access and use, including what fits into a woman's lifestyle, will ultimately determine her preferred choice of prevention.
About the Trials
Pre-exposure prophylaxis (PrEP) is the use of medicine in advance of exposure to something potentially harmful, such as a disease or condition. In the context of HIV, it is the use of anti-retroviral medicine by HIV-negative people before sexual activity or other high-risk behaviours.
Microbicides are being developed as products that could be topically applied by a receptive sex partner either in the vagina or the rectum to reduce risk of becoming HIV infected during sex. Microbicide candidates are being formulated as vaginal gels, suppositories or slow-releasing vaginal rings.