In a South African microbicide trial known as CAPRISA 004, 1% tenofovir (an antiretroviral) gel reduced HIV-negative women’s risk of acquiring HIV infection by approximately 39 percent overall over 30 months. The trial also found that 1% tenofovir gel reduced the risk of herpes simplex virus type 2 (HSV-2) infection by over 50% among women in the trial who were not infected with HSV-2 at the beginning of the trial.
This landmark trial released earlier this year provided the first evidence that a microbicide can reduce women’s risk of HIV infection when it is vaginal intercourse. However, it did not provide all of the answers needed to introduce use of 1% tenofovir gel as a new HIV prevention strategy.
Dr Zeda Rosenberg, Chief Executive Officer of the International Partnership for Microbicides Research (IPM), said CAPRISA 004, which took place in South Africa, had created a platform for further research into the effectiveness of using tenofovir for prevention.
The much anticipated VOICE (Vaginal and Oral Interventions to Control the Epidemic) trial is currently testing once-daily dosing of 1% tenofovir gel along with two forms of oral pre-exposure prophylaxis (PrEP) in preventing HIV infections among heterosexual people living in Malawi, South Africa, Uganda and Zimbabwe.
VOICE is different from CAPRISA 004 in that it is testing whether inserting tenofovir gel every day reduces the risk of HIV infection for women’as opposed to applying it up to 12 hours before sex and within 12 hours after sex. The results of the VOICE trial are expected in 2012 at the earliest.
A new trial is also being planned by a consortium of leading South African researchers and would take place primarily in South Africa. It is being designed to test the same dosing strategy as CAPRISA 004 in women aged 16 to 30 years old in a variety of settings. It will also seek to establish the safety of the gel in sexually active 16 and 17-year-olds (enrolling women of these ages, who were excluded from CAPRISA 004), and gather more information on 1% tenofovir gel as a tool for preventing HSV-2 infection.
The other proposed trial is being developed by the Microbicides Development Programme and would be conducted in other African countries comparing two different dosing schedules. One dosing schedule would be the CAPRISA 004 dosing regimen, where women following this regimen would be instructed to insert one applicator of gel as close to the time of sex as possible, but no more than 12 hours before, and one applicator within 12 hours after sex, with a maximum of two doses in 24 hours. The other dosing schedule to be tested would be single-use dosing, where women would be instructed to insert a single application of the gel before sex or, failing that, immediately after sex.
A vaginal ring containing the ARV Dapivirine is currently undergoing large safety trials in South Africa and Belgium. A larger efficacy trial involving 3 000 women is planned for September next year.
Rosenberg said a vaginal ring would be advantageous in terms of cost and adherence since it would be active for a longer period while in the woman’s body.
‘Women would insert the ring into their vagina. It would stay there for a month or longer. The ring concept is not new since it is being used successfully in the United States for birth control and hormone replacement. Instead of something they would apply every day, women could just insert the ring once and forget it’s even there,’ she said.
Rosenberg said the HIV research industry drew a lot of hope from the result that came from the iPrEx trial which looked at the effectiveness of using the Truvada, a combination ARV drug. IPrEx showed an average HIV reduction of 43,8 percent in men who have sex with men and a further reduction in those who took the drug more consistently.
‘It’s an addition to the scientific base that ARVs could be used to prevent HIV transmission. We knew that ARVs could prevent mother to child transmission of HIV but now we’ve also learned that it could reduce the chances of men who have sex with men getting HIV,’ she said.
Rosenberg said the political will was there and donors understood the scale of the problem, but that the current economic situation also posed a challenge.