About Microbicides Fact Sheet

Fact Sheet - About Microbicides

Fast Facts

What Will it Take to Discover a Safe and Effective Microbicide?

Testing many products is necessary before finding even one microbicide that will be safe and effective against HIV and also easy and acceptable to use. Different products work in different ways and/or in how they’re used. One approach may suit some people but not others. Individual needs and preferences can also change, which is why a range of products is needed. A handful of candidate microbicides are in various stages of clinical study; additional compounds are in early stages of development.

Drug development is a long and arduous process, often taking up to 20 years for a product to be approved for general use. Thousands of potential compounds may be considered during drug discovery but only the most promising are subjected to rigorous laboratory and animal studies, and fewer still make it to trials with people.

Clinical trials are carried out in several phases under the oversight of regulatory and research authorities and according to strict ethical and scientific guidelines. Phase I trials are designed to evaluate safety in a small number of people and for short periods, say, one to two weeks. If results of a Phase I study suggest the product is safe, investigation may progress to a Phase II trial to track its safety in more people over longer periods of time. Phase IIb and III trials are much larger studies that are designed to determine a product’s effectiveness, as well as to gather more safety information. They can take years to conduct, and their results weigh heavily in a regulatory agency’s decision whether to approve the product for widespread use.

Vaginal Microbicides

An Overview

The idea for a microbicide-like product was first proposed about 25 years ago by reproductive health specialists and advocates who recognized the need for female-controlled HIV prevention methods. One of the first products considered was the spermicide nonoxynol-9, but clinical trials found it neither safe nor effective against HIV. Trials of other so-called first generation microbicides also yielded disappointing results. These included products that were meant to strengthen natural defenses in the vagina or create a barrier to protect target cells. Researchers now are evaluating microbicide products that incorporate ARV drugs, including ARVs commonly used in HIV treatment.

The most studied ARV-based microbicide is tenofovir gel, which was found safe and effective in reducing HIV risk in women who used it before and after vaginal sex in a study called CAPRISA 004 but not effective in another study known as VOICE, which was designed to evaluate its daily use (as well as daily use of either the oral ARV tablet tenofovir or Truvada®). Tenofovir gel continues to be evaluated in an ongoing Phase III trial, FACTS 001, testing the same regimen as CAPRISA 004 – before and after sex. Depending on the outcome of FACTS 001, CONRAD, as co-licensee of the product, may seek regulatory approval of tenofovir gel.

As an alternative to vaginal gels, researchers are evaluating other formulations, including paper-thin quick-dissolve vaginal films that after insertion would melt away and disperse active drug to protect cells in the vagina. Films are in the early phases of clinical testing. Vaginal rings, flexible products that fit comfortably inside the vagina and provide sustained delivery of drugs over a period of time, are being tested in both early phase studies and Phase III trials. Vaginal ring products are already used in many countries to deliver hormonal contraception. For HIV prevention, the dapivirine ring is the first vaginal ring – and the first HIV-prevention product intended for monthly use – to enter efficacy testing. As sister studies, ASPIRE, which is being conducted by the Microbicide Trials Network (MTN), and The Ring Study, being led by the International Partnership for Microbicides (IPM), are designed to provide the strength of evidence to support potential licensure of the dapivirine vaginal ring for preventing HIV in women. IPM, which developed the dapivirine ring, is the regulatory sponsor and license holder of the product.

Vaginal rings containing both an ARV and a contraceptive are also being developed that would potentially provide women both HIV protection and contraception in a single product. Phase I trials could begin in 2014.

Clinical Trials Snapshot

Tenofovir Gel

Vaginal Rings

Rectal Microbicides

An Overview

Although the majority of microbicide research has focused on products to prevent HIV through vaginal sex, anal sex is common among men who have sex with men (MSM) and practiced by women around the world. According to some estimates, the risk of infection through anal sex is 20 times greater than vaginal sex because the rectal lining, the mucosa, is thinner and much more fragile than the lining of the vagina.

An important first step to the development of rectal microbicides has been evaluating the rectal safety of microbicides originally formulated as vaginal gels, in particular, tenofovir gel. An early study found that the vaginal formulation of tenofovir gel caused gastrointestinal side effects when used in the rectum, so researchers tested a reformulated version of the gel with less glycerin in a follow-up study called MTN-007. That study found the reduced glycerin gel safe, acceptable and better tolerated than the vaginal gel when used in the rectum.

MTN researchers are currently conducting MTN-017, the first Phase II trial of a rectal microbicide, to test whether the reduced glycerin formulation of tenofovir gel is safe and acceptable among MSM and transgender women in Peru, South Africa, Thailand and the United States, including Puerto Rico. In another trial called MTN-014, being conducted among women in the United States, researchers are examining drug absorption patterns in both rectal and vaginal tissue when the gel is applied either vaginally or rectally.

Research teams are also focusing on products developed specifically for use in the rectum. Two ongoing studies, part of the Combination HIV Antiretroviral Rectal Microbicide (CHARM) Program, are testing a microbicide gel containing the ARVs tenofovir and maraviroc to find out whether the combination product is safe and acceptable as a rectal microbicide. Another study, Project Gel, is assessing rectal microbicide safety and acceptability in young men who have sex with men.

Clinical Trials Snapshot

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More information about microbicides and other HIV prevention approaches is available from AVAC:Global Advocacy for HIV Prevention http://www.avac.org/, and International Rectal Microbicide Advocacy http://www.rectalmicrobicides.org/.

The Microbicide Trials Network (MTN) is an HIV/AIDS clinical trials network established in 2006 by the National Institute of Allergy and Infectious Diseases with co-funding from the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Institute of Mental Health, all components of the U.S. National Institutes of Health. Based at Magee-Womens Research Institute and the University of Pittsburgh, the MTN brings together international investigators and community and industry partners whose work is focused on the development and rigorous evaluation of promising microbicides – products applied inside the vagina or rectum that are intended to prevent the sexual transmission of HIV – from the earliest phases of clinical study to large-scale trials that support potential licensure of these products for widespread use. More information about the MTN is available at www.mtnstopshiv.org.

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