Microbicides

Introduction

I. 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.

II. 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.

III. 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:

IV. 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.

What we know

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Putting it into practice

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Tools and Curricula

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Learn more

HIV/AIDS: Microbicides

United States Agency for International Development. (2011).

This webpage provides information on U.S. Agency for International Development (USAID) activities related to microbicides, including the agenda, presentations, and meeting report of the high-level Microbicides Stakeholders Meeting in late 2010. Readers can find information on the agency's financial support for microbicides development, their stance on the results of the Centre for the AIDS Programme of Research in South Africa 004 trial, partnerships for microbicide support and development, as well as current USAID activities on microbicides research and development.

View Microbicides Website



Regulatory Issues in Microbicide Development

Stone, A. (2009).

Because microbicides are a relatively new product, little guidance exists on the regulatory requirements needed at different stages of product testing and data necessary for licensure. To address this gap, the World Health Organization held six consultations in Europe, Africa, and Asia from 2002 to 2008. The first consultation drafted the minimal regulatory requirements for microbicide trials and eventual product licensing. Subsequent consultations opened a dialogue among in-country researchers, policymakers, and regulators about microbicide regulatory issues, with an aim to alleviate constraints to microbicide development. This report discusses the role of regulatory authorities in non-clinical and clinical microbicide studies, including safety, effectiveness, epidemiological principals, and pharmacology, as well as issues specific to microbicide use.

View Report (PDF, 578 KB)



Microbicide Research

CONRAD. (n.d.).

This webpage provides an overview of CONRAD's microbicide research activities, starting from some of the first microbicides developed in the 1990s to today's formulations that contain antiretroviral drugs. Readers can click on links to obtain more information on the development process for microbicides, as well as CONRAD's preclinical and clinical microbicide activities. In addition, information is available about their dual-protection microbicides that protect women from pregnancy in addition to sexually transmitted infections and/or HIV.

View Microbicides Website



Microbicides

Global Advocacy for HIV Prevention. (n.d.).

This webpage provides readers with links to microbicide information, including introductory information to those that may not be familiar with the topic. A microbicide fact sheet is available in English, Spanish, French, Portuguese, and Thai for readers to download and disseminate. Readers can also follow a link to a collection of microbicide resources, including question and answer sheets and summaries of ongoing microbicide clinical trials. Readers can also link to a page that provides breakdown of clinical trials: ongoing trials, trial results, and planned trials.

View Microbicides Website



Global Campaign for Microbicides

Global Campaign for Microbicides. (n.d.).

The Global Campaign for Microbicides promotes the rapid yet ethical development of and widespread access to HIV prevention options, especially for women. The organization collaborates with all sectors, from civil society to industry, and does not support any one product. This website includes information on microbicides, clinical trials, other prevention options such as female condoms and male circumcision, and more. Resources are available in English, French, Spanish, and Russian.

View Global Campaign for Microbicides Website



How Does It Work? Microbicides

Global Health Council. (n.d.).

This brief fact sheet clearly explains the biology of microbicides and how microbicides may work to help protect users from HIV, complete with references to selected research articles providing more detailed information. A useful graphic shows how a virus enters by disrupting the vaginal skin cell layers and also depicts how microbicides may be able to stop such disruption, and thus, viral entry.

View Website



International Partnership for Microbicides

International Partnership for Microbicides. (n.d.).

The International Partnership for Microbicides (IPM) is an organization founded as a product development partnership. Its mission is to speed the development of microbicides and other HIV prevention mechanisms for women in developing countries. Working with partners from academia to biotechnology companies to civil society organizations, IPM has several compounds in development and in various stages of clinical trials. Their website offers information on their work, different HIV prevention products for women, media resources, scientific articles, and other publications about microbicides.

View IPM Website



International Rectal Microbicides Advocates

International Rectal Microbicides Advocates. (n.d.).

International Rectal Microbicides Advocates is an organization of individuals worldwide working to advance research and development of safe, effective rectal microbicides for men, women, and transgender individuals to use for HIV prevention. Materials that can be accessed on their website include information on the safety of lubricants for anal use, scientific articles, media stories, fact sheets, and more. This highly interactive site includes blogs and subscription to a moderated listserv. Links are available to sister websites for Nigeria and for Latin America and South America.

View International Rectal Microbicides Advocates Website



The Medium Matters: Applicators are Crucial to Success of Microbicides

PATH. (n.d.).

Something as simple as what kind of applicator is used in microbicides can have a significant impact on the product--for example, its cost, usability, and safety. PATH provides an interesting perspective on product development by describing the considerations behind applicator design, their choices between using single-use applicators and multiple-use applicators, and user-testing. Through this description, readers can see the balancing act required to be able to meet women's needs while also making a product safe and affordable. PATH is now working to obtain regulatory approval for microbicide applicators so that they can quickly be made available once a microbicide becomes available.

View PATH Website



International Microbicide Conference

Sydney, Australia, 15-18 April 2012.

The biennial International Microbicides Conference, held in April 2012 in Sydney, Australia, focused on HIV prevention technologies, including the use of antiretroviral-based microbicides and pre-exposure prophylaxis (PrEP); adherence in clinical trials; innovative financing; dual prevention technologies; and new methods of preventing rectal transmission of HIV. In the keynote address, Dr. Salim Abdool Karim, co-principal investigator of the CAPRISA 004 trial, discussed implications and lessons learned nearly two years after the trial provided proof of concept for antiretroviral-based microbicides. In the opening plenary, Dr. Connie Celum of the University of Washington discussed the emerging evidence from recent oral and topical tenofovir-based PrEP trials that have demonstrated efficacy ranging from 39 to 75 percent. She emphasized the ongoing challenges of adherence, risk perception, and delivery of PrEP to most-at-risk populations. She urged researchers to continue to explore longer-acting products that are less adherence-dependent. To address the need for rectal microbicides, International Rectal Microbicide Advocates (IRMA) released a strategy document entitled The Map: Ensuring Africa's Place in Rectal Microbicide Research and Advocacy. Other presenters focused on a variety of topics, including multi-prevention technologies, access to microbicides, and recent findings from PrEP trials. The conference closed with a presentation from Gina Brown, U.S. National Institutes of Health, and Stephen Becker, Bill & Melinda Gates Foundation, who announced that the biennial microbicide conference will be replaced with a biennial global HIV prevention conference focusing on vaccines, microbicides, and oral PrEP.

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