Microbicides and Biomedical Prevention at EACS 2013
The first day of the European AIDS Conference last week in Brussels featured a satellite symposium on HIV microbicides and pre-exposure prophylaxis (PrEP), sponsored by the CHAARM (Combined Highly Active Antiretroviral Microbicides) Project and the European AIDS Treatment Group.
Biomedical prevention is one of the most promising areas of HIV research. Large clinical trials have shown that oral Truvada (tenofovir/emtricitabine) and tenofovir vaginal gel can dramatically reduce the risk of HIV infection, but the main challenge for PrEP is the need for a high level of adherence. Researchers hope that new formulations (such as vaginal rings or long-acting injectables) and different administration schedules (like using pills or gels before or after sex rather than every day) might help improve adherence.
The advantages of oral PrEP include familiarity and decades of experience, explained Sheena McCormack from the U.K. Medical Research Centre. Topical products, on the other hand, “get where they need to go,” rapidly achieving high drug levels in genital tissues while lower blood levels lead to less toxicity. Topical products also offer more opportunity for multipurpose use such as combining antiretrovirals and hormonal contraceptives in a single gel or ring.
Biomedical prevention trials now or soon to be underway include a study of oral maraviroc (Selzentry) alone and in combination with tenofovir or emtricitabine and the IPERGAY trial looking at Truvada PrEP taken within 24 hours after unprotected sex. Tenofovir gel—already shown to be effective for vaginal use in the CAPRISA 004 trial—is now being studied for rectal use in the Phase 2 MTN-017 trial, with sites in the U.S., Thailand, South Africa, and Peru.
The DAPIDAR trial is evaluating a gel containing the NNRTI dapivirine. Two trials of dapivirine-containing vaginal rings have enrolled about 75% of their targeted number of women in several countries in Africa. A pair of long-acting injectable antiretrovirals—an extended-release formulation of rilpivirine (TMC278) and GSK1265744—appeared safe in preclinical studies and are now entering Phase 2 trials.
Results from most of these studies, McCormack predicted, should be available by the end of 2015 or early 2016.
Janneke van de Wijgert from the University of Liverpool gave a presentation on the safety challenges of vaginal and rectal microbicides. It is important that products not disrupt the vaginal flora or “microbiota” in ways that discourage friendly bacteria or encourage growth of harmful pathogens. The rectal micro-environment is “much more vulnerable” than the vagina, she explained, in part due to its thinner layer of cells. In both the vagina and rectum, inflammation increases susceptibility to HIV infection.
In an effort to do no harm, microbicide research must take into account a range of interconnected factors, including the presence of other sexually transmitted infections, the role of hormonal contraception, the effects of semen, and traditional practices such as vaginal washing after sex.
Guido Vanham from the Institute of Tropical Medicine in Antwerp reviewed some of the compounds further back in the CHAARM development pipeline. These include CD4 mini-proteins, single-chain antibodies found in llamas, triazine NNRTIs, and LEDGF inhibitors (LEDGINs). These new compounds probably will not be used as single agents, he said, but offer potential for combination approaches.
Finally, Harriet Langanke of the German Sexuality and Health Foundation took a turn away from the science to discuss the marketing of microbicides. To encourage adherence, she said, new products should be “at least as easily available as male condoms” and packaging should be either discreet or sexy—”something you wish to show off, like a smart phone.”
Liz Highleyman is a freelance medical writer and editor-in-chief of HIVandHepatitis.com.