Last year marked a promising new chapter in the field of oral and topical antiretroviral (ARV)-based prevention. Results of the Centre for the AIDS Programme of Research in South Africa (CAPRISA) 004 trial showed that a microbicide candidate consisting of a 1% tenofovir gel was able to reduce HIV incidence in a group of South African women by 39%. Several months later, a study (known as iPrEx) of nearly 2,500 men and transgendered women who have sex with men at 11 clinical sites in the US, South Africa, Brazil, Thailand, and Ecuador showed that daily administration of the ARVs emtricitabine (FTC) and tenofovir (TDF) was 44% effective in protecting against HIV infection.
In the next several years, results of ongoing studies will show whether this strategy known as pre-exposure prophylaxis or PrEP is also effective in reducing the risk of HIV transmission among other high risk groups, such as injection drug users or serodiscordant couples.
Today at the 18th Conference on Retroviruses and Opportunistic Infections (CROI) in Boston, both PrEP and post-exposure prophylaxis or PEP (the administration of ARVs directly after HIV exposure to prevent infection) were the subject of several talks.
The US Centers for Disease Control and Prevention (CDC), which has played a major role in the preclinical and clinical testing of PrEP, released new data from non-human primate studies that suggests TDF and FTC are not the only ARVs that may have a role in preventing HIV. CDC researchers Charles Dobard and Walid Heneine presented data showing that the administration of a vaginal gel containing raltegravir, an ARV that blocks the virus’s integrase enzyme, prevented HIV infection in five of six pigtail macaques when applied topically three hours after the animals were exposed to a strain of a simian immunodeficiency virus/HIV hybrid known as SHIVsf162p3. These animals remained uninfected after being exposed to SHIV 20 times, while four animals that received a placebo gel became infected after an average of 10 SHIV exposures.
This is the "first evidence that a vaginal gel can protect monkeys when used as post-exposure prophylaxis," said Heneine. This is also the first time this ARV has been tested in topical prophylaxis, and according to Dobard, these results suggest integrase inhibitors may be useful in both PEP and PrEP.
Because raltegravir was able to protect when applied following SHIV exposure, it also suggests that a raltegravir-based PrEP regimen might be more forgiving if adherence isn't perfect and a woman failed to apply the gel prior to sex.
Craig Hendrix of Johns Hopkins University presented data from a Phase II study comparing oral administration of TDF with topical application of a TDF microbicide gel in sexually active women. This study showed that the concentration of TDF in vaginal tissue was 100-fold greater following topical application. But Hendrix acknowledged that the concentration associated with protective efficacy is unknown so the concentrations from oral administration may also be adequate.
In this study, known as MTN-001, women in Africa reported having an equal preference for the oral and gel administration, whereas women in the US said they were more likely to use the pill form.
Tomorrow there will be several presentations on different aspects of the iPrEx data, as well as results of a mathematical modeling study on the cost effectiveness of implementing PrEP.
-written by Regina McEnery and Kristen Jill Kresge