Last week, UNAIDS announced that at least 56 countries have stable or declining incidence of HIV/AIDS. Yet on World AIDS Day this week, there are still two new infections for every person put on antiretroviral therapy. However, a series of promising new scientific results in prevention, including three breakthrough trials in just 16 months, offer the first glimmer of hope that we may finally be able to achieve the "three zeros" -- zero new infections, zero stigma/discrimination and zero AIDS deaths.
Start with male circumcision, which studies in Kenya, South Africa, and Uganda have shown to reduce HIV acquisition by up to 60%. Funders such as the U.S. government, The Bill & Melinda Gates Foundation and several African countries are seizing on these findings -- and WHO's and UNAIDS' conclusion that "the efficacy of male circumcision ... has now been proven beyond reasonable doubt" -- to promote male circumcision actively as part of overall prevention efforts.
Meanwhile, last year's release of the RV144 trial in Thailand, which provided the first evidence of the effectiveness of any vaccine in preventing HIV infection, and the discovery of new broadly neutralizing antibodies have renewed hope in the promise of HIV vaccines in the 21st century.
But perhaps the greatest excitement centers on Pre-Exposure Prophylaxis (PrEP), involving preventive use of antiretroviral drugs already proven in HIV/AIDS treatment. PrEP offers women in particular a prevention strategy for dealing with partners who refuse or are unable to use condoms or whose faithfulness is in question.
The scene was electric in Vienna, Austria, last July when the Centre for the AIDS Programme of Research in South Africa (CAPRISA) - with FHI and CONRAD as collaborating partners - announced that a form of topical PrEP, a vaginal gel containing the antiretroviral agent tenofovir, had been shown to reduce acquisition of HIV infection in women by 39% and of herpes by 51%. An even greater rate of protection -- up to 54% -- was recorded among women able to adhere to the trial regimen.
This CAPRISA 004 trial was the first to show a statistically significant result through use of topical gels -- and subsequent mathematical modeling suggests that tenofovir gel could prevent 1.3 million HIV infections and 800,000 deaths over two decades in South Africa alone.
Next year, the International Partnership for Microbicides will initiate two trials to test another form of topical PrEP, a vaginal ring containing a new antiretroviral drug, dapivirine. In addition, CONRAD recently obtained funding from the U.S. Agency for International Development (USAID) to develop rings containing tenofovir and a contraceptive.
Oral PrEP is also being investigated. Last week, initial results from the IPrEx trial, led by the University of California at San Francisco with funding from the U.S. National Institutes for Health (NIH) and the Gates Foundation, indicated that a once-daily oral dose of Truvada® (tenofovir/emtricitabine) is 44% effective in preventing HIV infection in high-risk men who have sex with men (MSM). As in CAPRISA 004, men who best adhered to the regimen achieved even higher levels of protection.
Results are expected in 2012 from the FEM PrEP trial oral prep trial led by FHI and funded by USAID testing Truvada and in 2013 from the Partners PreEP trial of Truvada and Viread, led by the University of Washington with funding from Gates. The VOICE (Vaginal and Oral Interventions to Control the Epidemic) trial funded by NIH, brings the topical/oral PrEP field together by comparing the effectiveness and practicality of both Viread and Truvada pills and tenofovir gel.
All in all, HIV prevention is on a roll. But major scientific and practical challenges lie ahead. Further PrEP studies are required to validate effectiveness, establish dosage, determine long-term safety, assess impact on sexual behavior and evaluate any effect on HIV drug resistance. But in these days of economic challenges, lack of money for trials is already threatening to slow follow-up research on the CAPRISA 004 and IPrEx successes.
Other practical issues need to be addressed as well once these products are ready for the market. Cultural, marketing and logistical barriers must be overcome to increase demand and, since avoiding development of drug resistance requires PrEP to be used only by people known to be free of HIV, we will need to expand access to education and testing and implement protocols to avoid sharing and theft of prophylactic treatments.
Because the science is so promising, we urge everyone -- from scientists to policymakers to the public -- to use World AIDS Day, Dec. 1 as a catalyst to build on these advances by mobilizing communities to embrace HIV prevention as a social norm and advocate for the funding required for the next round of research. Much work remains to be done, but by building support for these critical next steps, we can also build hope for a future World AIDS Day free of AIDS.
See the Global Health Council Position Paper on HIV/AIDS.