Definition of the Prevention Area
Microbicides are products formulated for individuals to apply topically (vaginally or rectally) to reduce their risk of HIV and possibly other sexually transmitted infections. At present, this approach is experimental, although several broad-spectrum microbicides have been clinically evaluated. Microbicides comprise a subset of approaches to pre-exposure prophylaxis (PrEP); oral approaches to PrEP are addressed in a separate entry.
Epidemiological Justification for the Prevention Area
In generalized epidemics, women are at a disproportionate risk of HIV infection for biological as well as social reasons. Although condoms are highly effective in preventing HIV transmission, it can be difficult for women to negotiate safer sex because the male partner often controls whether a condom is used. Microbicides were initially proposed as a woman-controlled or -initiated prevention method for vaginal application, something a woman could use to protect herself.
The first microbicides studied were broad-spectrum compounds that were expected to inactivate HIV and other microbes by enhancing vaginal pH or by coating cell surfaces, preventing the binding of viruses or the entry of microbes into tissue. None of these approaches proved effective.
However, clinical trial results released in 2010 by the Centre for the AIDS Programme of Research in South Africa (CAPRISA) provided the first proof of concept for microbicide efficacy. This study, CAPRISA 004, found that a topical gel formulation of the antiretroviral drug tenofovir significantly reduced the risk of acquiring HIV and herpes simplex virus 2 (HSV-2) in women who use it regularly around the time of sex. However, in late 2011, the gel arms of another clinical trial evaluating daily use of one percent tenofovir gel were stopped early by the trial's data safety and monitoring board because there was no evidence that the gel was effective in reducing the risk of HIV acquisition. (This trial was also evaluating oral tenofovir and oral Truvada). Further analysis of data from this trial, known as VOICE (Vaginal and Oral Interventions to Control the Epidemic), is needed to explain the discrepancy between the two trial results.
Another trial evaluating vaginal use of one percent tenofovir gel is underway using the same dosing schedule as in CAPRISA 004. This trial, FACTS 001, is being conducted by the Follow-on African Consortium for Tenofovir Studies (FACTS) which expects to have data available in 2014. If FACTS confirms effectiveness of one percent tenofovir gel, additional steps will be needed before it can be licensed and marketed. Two safety and effectiveness trials of a vaginal ring containing dapivirine are scheduled to start in 2012.
Researchers are also evaluating whether these products could be safe and effective when applied rectally, given that anal sex carries an even higher risk of HIV transmission for heterosexuals and men who have sex with men. Developing a rectal microbicide is more challenging because the rectal mucosa is highly susceptible to HIV infection. Also, the colorectal tract has a greater surface area than the vagina, requiring a rectal microbicide to have greater coverage. Trials of a rectal formulation of tenofovir gel are moving forward.
Core Programmatic Components
Further studies are needed to confirm the safety and efficacy of tenofovir gel and other products being developed; it will be several years before this or any other microbicide is marketed. In the meantime, policymakers and program directors need to work closely with the community to put this potential prevention tool to best use. The following key activities will be necessary:
- Support of research to assess how the microbicide might be accepted and used in the local setting. What impact will it have on sexual risk-taking?
- Development of educational materials and campaigns to promote adherence and correct use while helping people understand the potential limitations of products that are only partially effective.
- Buildup of a stable supply chain and strategic distribution plan to ensure access to those who need the microbicide.
- Ensuring access to regular and routine HIV testing, especially rapid point-of-care HIV tests, to reduce the risk that people who are HIV-positive and are unaware of their HIV status will use the product.
- Performing surveillance for adverse events and for detection of any increase in HIV transmission or the possibility of individuals not yet on antiretroviral therapy developing drug resistance.
Current Status of Implementation Experience
While an approved microbicide is not yet available, the clinical trials in Africa and India provide insights into how best to introduce microbicides into communities and fuel hope that women-driven prevention technology might further women's empowerment. For instance, one group in Pune, India, has explored how discussion of microbicides among couples could enhance partner communication about sex.
While the success of the CAPRISA trial is promising, additional work will be necessary to complete the critical next phases of research that could lay the groundwork for large-scale rollout. A number of additional trials over the coming years should deliver further results.