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.
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The PDF and text below were last updated in March 2013.
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
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 did not reduce risk in women counseled to use it on a daily basis. The tenofovir gel arm was stopped early after interim DSMB review in 2011 found it to be safe but not effective in the study population.
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 2013. One hundred eighty-six men who have sex with men have been 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 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, data from the VOICE trial indicate that many participants did not adhere to a daily gel regimen, highlighting the challenge of developing and delivering a product women can and want to use.
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.) Other options are in early stages of preclinical and clinical development, including vaginal inserts and films.
Dapivirine vaginal ring:
- ASPIRE (MTN 020): Safety and effectiveness trial of dapivirine vaginal ring, inserted once every four weeks, in nearly 3,500 women. The trial began enrolling women at sites across five countries in sub-Saharan Africa in August 2012.
- The Ring Study (IPM 027): Safety and effectiveness trial of dapivirine vaginal ring, inserted once every four weeks, in 1,650 women. The trial began enrolling women at sites across four countries in sub-Saharan Africa in June 2012.
- 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 the second quarter of 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/pxrd.
When are results
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, was launched in 2012. Results from the FACTS 001 trial of 1% tenofovir gel are expected in 2013. Dapivirine ring studies, began enrolling in 2012 should yield results in 2015.
1 CAPRISA 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. More on past trials at www.avac.org/trials/microbicides.