The results of two studies presented last week at the Conference on Retroviruses and Opportunistic Infections (CROI), held in Montreal, signal that there is progress being made on HIV prevention tools designed specifically for women’s use.
One of the studies presented the results of a clinical trial conducted by the Microbicides Trial Network, examining the efficacy of two candidate microbicides – gels, creams, foams, and depositories developed for physical application inside the vagina, to halt sexual transmission of HIV from males to females. The trial, known as HPTN 035, enrolled 3,099 women at sites in South Africa, Malawi, Zambia, Zimbabwe, and the United States, and tested two candidate microbicides: Pro2000 and BufferGel. The study found that women offered PRO2000 gel plus condoms had 30 per cent fewer HIV infections than those offered only condoms or condoms plus a placebo gel. However, the study also found that BufferGel did not reduce the risk of HIV in women.
Though the PRO2000 results were not statistically significant, this is the first time that a microbicide trial has shown “proof of concept,” or proof that the idea of using a product applied to the vagina could work to prevent transmission of HIV. Anna Forbes, Deputy Director of the Global Campaign for Microbicides, expressed hope that these results will improve morale among those who were losing hope that a candidate microbicide trial would yield positive results – thus far, all previous clinical trials have either ended prematurely due to safety concerns, or have not reduced the risk of HIV in women.
“I think that it will encourage funders and researchers and government officials to see that there is reason to believe that the concept of a microbicide may actually work…. The trends in the data certainly suggest that there is a possibility [that a microbicide could prove effective] and this is the first time we’ve even seen that,” Forbes said.
Currently, Pro2000 is being tested in another clinical trial known as MDP 301. This trial has enrolled 9,000 women in Zambia, South Africa, Tanzania, and Uganda, and the results are expected in November of this year.
“The trial is three times larger than the HPTN 035 trial, so we feel that there is a good chance that it will provide us with a much more accurate reading on whether the product is effective or not,” Forbes said.
In another study presented at CROI, researchers Dr. Charles Dobard and Dr. Walid Heneine, both from the U.S. Centres for Disease Control, found that when applied as a gel prior to vaginal simian human immunodeficiency virus (SHIV) exposure, a single antiretroviral drug (tenofovir) was just as effective as two antiretroviral drugs (tenofovir and FTC) in preventing SHIV infection in female macaques; this approach, is called Pre Exposure Prophylaxis (PrEP).
Dobard was quick to mention, however, that results from clinical trials are necessary before it can be determined to what extent, if at all, PrEP is effective in preventing HIV transmission.
“People feel that this particular intervention is promising, but again, these are animal studies and so we are waiting for the studies from the human clinical trials, and that’s going to allow us to really hopefully validate our animal model,” Dobard said.
Forbes agreed that Dobard et al.’s results were promising, but that more research is needed.
“It’s certainly always good news to see positive results in animal trials. I think we’ve all learned the hard way that that doesn’t necessarily translate to positive results in people, but it’s always a step in the right direction,” Forbes said.
Currently, there are a number of clinical trials planned or under way to test the efficacy of antiretroviral-based gels, including one that will test a tenofovir vaginal gel. The results of the first trial are expected in 2010.
Dobard explained that the antiretroviral-based gels may prove more effective than the first-line microbicides such as Pro2000, because they are specific to HIV.
“Tenofovir and FTC – they are inhibitors of reverse transcription of HIV, and their primary mechanism is that they are nucleocide anologues – so they block reverse transcription by basically incorporating analogues that are dead end products, so that it basically shuts down reverse transcription,” Dobard explained.
Pro2000, however, is an entry and fusion inhibitor that binds to a broad spectrum of viruses and bacteria, to prevent them from binding to and infecting healthy cells.
Forbes, for one, is confident that the past week’s announcements are a sign that the development of an effective microbicide is possible.
“We believe very strongly that it is possible to put an HIV prevention tool for women in women’s hands, and the evidence produced this week by HPTN 035 only strengthens our belief in that,” Forbes said.