This section provides basic information on microbicides, one of the options being tested now as part of the effort to identify additional tools to reduce the risk of HIV transmission.

You can also download this page as a microbicide fact sheet (PDF) in English, French, Portuguese, Spanish and Thai.

Text below and English PDF last updated January 2012. Other PDF's last updated in February 2011.

What is a microbicide?
The term microbicide refers to substances being studied that could be used in the vagina and/or rectum to reduce the risk of HIV transmission during sex. Microbicides could come in a number of forms, including creams, gels, films, slow-release vaginal rings, enemas and suppositories that could be used vaginally or rectally.

What are the most recent developments in the microbicides field?¹
The most advanced candidate—and the only candidate to show efficacy to date—is 1% tenofovir gel, a topical formulation of the antiretroviral drug, tenofovir. Key developments related to this candidate are described below. For more information on the full microbicide pipeline see www.avac.org/trials/microbicides.

One trial to date has shown evidence that a microbicide—1% tenofovir gel—reduces HIV risk in women:

• The CAPRISA 004 trial in 889 South African women found that 1% tenofovir gel reduced women’s risk of HIV infection via vaginal sex by 39 percent overall. Women in the trial were counseled to use the gel within 12 hours before and after sex, a regimen known as BAT-24. There is a proposed open-label study (where all participants are offered the product being tested and there is no placebo) of 1% tenofovir gel, called CAPRISA 008. This study would look at effective ways to deliver the gel in communities where the CAPRISA 004 trial took place.

One trial to date has shown that 1% tenofovir gel does not reduce HIV risk in women:

• The VOICE trial, which was designed to test both oral (pill form) and topical (gel form) ARV-based prevention found that 1% tenofovir gel did not reduce risk in women counseled to use the gel on a daily basis. The trial halted the gel arm after an independent data and safety monitoring board found equivalent rates of HIV infection in active and placebo gel recipients.

One trial of 1% tenofovir gel is ongoing in women:

• FACTS 001 is a large-scale trial of tenofovir gel in South African women, which began enrolling in October 2011. The trial is testing the same BAT-24 dosing strategy evaluated in CAPRISA 004. FACTS 001 results are expected in 2014.

One trial of a rectal formulation of 1% tenofovir gel is planned:

• MTN 017 is the first-ever Phase II trial of a rectal microbicide candidate, a rectal formulation of 1% tenofovir. It is scheduled to begin in the second quarter of 2012. Over 200 MSM will be enrolled at sites in Peru, South Africa, Thailand and the United States.

What is happening now?
The field is looking to the results of FACTS 001 and the analysis of the VOICE trial to learn more about how 1% tenofovir gel can be used as an HIV prevention tool. At the same time, many steps are underway to prepare for potential introduction of 1% tenofovir gel if it does prove effective. 1% tenofovir gel is a novel product. Unlike oral PrEP, which involves a product already in use for HIV treatment, the gel has never been manufactured at large scale (to meet needs outside of a clinical trial). Additionally, little is known about the types of programs that will be best-suited to deliver the gel to women. No other topical HIV prevention strategy has been brought to market. It is thus important to identify which organization or structure will assume leadership and final decision making in driving forward 1% tenofovir gel development. This strategy should include project timelines for all clinical regulatory, commercial and policy activities to provide a realistic sense of timing, funding and effort. This includes confirming the cost of goods (and the potential for cost reductions) and the timelines, for 1% tenofovir gel with its current applicator as well as developing implementation research strategies and budgets in key areas, such as service delivery, provider training and marketing. There are still questions about 1% tenofovir gel, but if the product does move into wider use and the field waits to develop implementation plans until all of these questions are addressed, it will be too late.

What is in the pipeline for microbicides of the future?
New delivery strategies
The majority of microbicide candidates in testing today are formulated with antiretroviral (ARVs) drugs and many current and past microbicide products have been gels. For the first time, a vaginal ring will be tested in large-scale microbicide safety and effectiveness trials for HIV prevention. The slow-release ring is manufactured with dapivirine, which is an ARV that was initially developed for use as treatment but when its developer, Tibotec Pharmaceuticals, decided they would not pursue it further for treatment, other scientists thought it might work as a microbicide for prevention. Tibotec granted the International Partnership for Microbicides (IPM) a license to use the drug in the development of a microbicide. (In addition to the ring study, dapivirine is also being tested in vaginal gel form.)

• Dapivirine vaginal ring:
• ASPIRE (MTN 020): Planned safety and effectiveness trial of dapivirine vaginal ring, inserted once every four weeks, in nearly 3,500 women to be enrolled at sites across five countries in sub-Saharan Africa.
• The Ring Study (IPM 027): Planned safety and effectiveness trial of dapivirine vaginal ring, inserted once every four weeks, in 1,650 women to be enrolled at sites across four countries in sub-Saharan Africa.
• MTN 013/IPM 026: Phase I safety study in women who are randomly assigned to use either a vaginal ring containing two ARV drugs (dapivirine and maraviroc), a ring containing maraviroc alone, a ring that contains dapivirine alone, or a ring with no active drug, inserted once every four weeks. This is the first ARV combination vaginal ring to enter clinical trials. Results are expected in early 2013.

New mechanisms of action
There is also research into non-ARV-based candidate microbicides, like those that may act as a physical barrier at the mucosal lining of the vagina or rectum. Most of these trials are in the earlier stages, details of which can be found at www.avac.org/trials/microbicides.

When are results expected?
CAPRISA 008, a planned follow-on study to CAPRISA 004, which would evaluate the effectiveness of distributing 1% tenofovir gel in communities where CAPRISA 004 took place, is planned to start in 2012. In 2013, the complete data set from the VOICE trial is expected, which should shed some light on why 1% tenofovir gel was not effective at reducing risk for women in that study. Results from the FACTS 001 trial of 1% tenofovir gel are expected in 2013. Dapivirine ring studies, planned to begin in 2012 should yield results in 2015.

Priorities for 2012
AVAC’s Playbook 2012 sets out top strategic goals and priorities in HIV prevention for ourselves—and for the world. Here’s what we have to say about microbicides. For more, visit www.avac.org/playbook.

¹CAPRISA 004 is the first (and so far only) safety and effectiveness trial to show that a microbicide could be effective at reducing risk, but there have been a number of microbicide effectiveness trials of various products, none of which were effective at reducing risk—for more on past trials visit www.avac.org/trials/microbicides.