Microbicides are substances capable of protecting people from infection by microbes, such as viruses or bacteria, by either directly killing or disabling the microbes or physically preventing them from entering human cells. In the context of HIV prevention, the term microbicide generally refers specifically to products that are being designed for topical (vaginal or rectal) application to reduce the user’s risk of acquiring HIV and possibly other sexually transmitted infections (STIs)1 during intercourse. When interest in this potential HIV-prevention strategy arose in the late 1980s, they were called ‘virucides’. The term 'microbicides' has since replaced 'virucides' to include products that could be active against a wide range of infections, not just viruses.

In July 2010, for the first time, a microbicide was pronounced to be both safe and effective. It is a vaginal gel containing an anti-retroviral drug called tenofovir and its properties and effectiveness are described below (see CAPRISA trial: the first microbicide proven to be effective). In the previous two decades, dozens of other candidate microbicides had been tested prior to this breakthrough. This rate of progress is characteristic of new drug development: literally hundreds, and sometimes thousands, of compounds are typically considered for each one that is ultimately approved for human use. In the case of microbicide research, however, the challenge of finding a successful product has been complicated by two distinctive factors:

  1. The difficulty of finding a product that can disable HIV while still being safe enough to apply frequently (daily or more often) to mucous membranes over time
  2. Chronic underfunding of the field, since private pharmaceutical companies and other developers have shown little interest in investing in such products.

 In 2008, a total of US$244 million supported microbicide research and development (R&D) globally, 85% being contributed by governments and multilaterals, 14% by the philanthropic sector and 1% by the commercial sector. By comparison, the 2008 investment in HIV vaccine R&D stood at US$868 million, with 84% contributed by governments and multilaterals, 12% by philanthropies and 4% by the commercial sector. Even with a comparable distribution of funding sources, microbicides received little more than a quarter of the support provided to vaccines. In 2004, about five times more was spent on vaccine R&D (US$933 million) than on microbicides (US$221 million).2

Frustration about underfunding of the microbicides field persists to this day. Dr Robin Shattock, in his opening plenary talk for the Microbicides 2010 conference, noted that the Thai vaccine trial (RV144) results had motivated AIDS vaccine researchers and advocates to demand enough resources to launch a Phase II vaccine trial every year. But, he added, “where is the money to see efficacy trials for [microbicidal] entry inhibitors? Where is the efficacy funding to see [microbicide] trials on combinations? I don’t see the microbicide field standing up and lobbying hard enough to do more clinical trials to get that human data that will inform the basic science.”3

Corporate sector investment has been miniscule because HIV vaccines and microbicides are thought unlikely to be highly profitable. As the Global Campaign for Microbicides notes: “microbicides are a classic ‘public health good’, an innovation that would yield enormous returns to society in terms of productivity and health benefits, but where the incentive structure of the private market fails to drive investment. Contraceptives and vaccines to prevent the diseases of poverty such as malaria are other public health goods.”4

Despite this, the prospects for developing at least partially effective microbicides are good, given the growing body of scientific expertise and political will that supports their development. The field’s main focus is on microbicides for vaginal use, a technically simpler challenge than designing safe and effective products for rectal use. Rectal microbicide R&D is also underway, however, and is attracting increased attention as research indicates that anal intercourse among heterosexuals may account for a larger share of HIV transmission than previously supposed.5

Both heterosexuals and gay men will likely experiment with rectal application of the first microbicides that become publicly available, just as they did with condoms. For this reason, products designed for vaginal use must also be tested for rectal safely so that, at minimum, labelling language can warn users against applying them rectally if they are shown to damage rectal tissue.

Undertaken in the late 1980s, the first microbicide research began with testing the currently available spermicides (contraceptives designed to kill sperm) to see if any were effective against HIV. Nonoxynol-9, the spermicidal agent in most non-prescription contraceptive products (including gels, foams and films), destroys HIV, but was proven ineffective as a microbicide because frequent use of it can irritate vaginal tissue and potentially exacerbate HIV risk.6

The development of ‘dual protection’ microbicides (products providing both microbicidal and contraceptive protection) is still a goal of the field, one that may be achieved by adding contraceptive agents to a proven microbicide, if no compounds emerge that are safe for frequent use while still active against both HIV and sperm. Social scientists have established that demand exists both for dual-protection products and for microbicides that are not contraceptive.7,8

Since condoms are inherently contraceptive, a non-contraceptive microbicide would offer women the novel option of reducing their HIV risk whilst allowing for the possibility of pregnancy  - a welcome alternative to women who desire pregnancy for their own reasons, to satisfy a partner or because of cultural expectations. A non-contraceptive microbicide that is bi-directional could also help HIV-positive women conceive with little risk of endangering HIV-negative partners.

A bi-directional microbicide would be one that not only protected the person applying it but also her or his partner. Thus, an HIV-positive woman might use a bi-directional microbicide to reduce her partner’s risk of becoming infected by HIV in her vaginal secretions, as well as to reduce her own risk of acquiring another strain of HIV if her partner were also HIV-positive. The possibility of bi-directional protection is of great interest to many microbicide advocates, especially those living with HIV.9 To determine its feasibility, however, we must first find a product that helps HIV-negative people to stay negative (primary prevention). Testing that product’s capacity for secondary prevention (blocking onward transmission from a positive partner) will require a different type of trial, one that enrolls serodiscordant couples rather than HIV-negative individuals. Due to the added complexity and cost of such trials, they will only be undertaken on products already known to work for primary prevention.

This issue is further complicated by the fact that most of the microbicide candidates now in clinical trials are antiretroviral-based. If used by people living with HIV who are not receiving antiretroviral combination therapy (such as by those unaware of their HIV infection), such compounds could lead to the development of drug-resistant HIV. It is likely that antiretroviral (ARV)-based microbicides will only be licensed for use by prescription (based on an HIV-negative test result) until more is known about whether, in fact, they could trigger the emergence of resistant virus when used by people living with HIV.

Microbicides are being developed in a range of formulations. The early, non-ARV-based candidates were gels inserted by applicator or applied to a vaginal diaphragm. Although five of these entered late-stage effectiveness trials, none were successful. 

The current generation of products are taking a variety of forms, some coitally dependent (to be applied before sex) and some not. These include gels, dissolving films and tablets, and vaginal rings designed to gradually release the microbicidal drug in the vagina for a month or more. HIV prevention is the primary goal for all of them, although secondary endpoints such as STI and/or pregnancy prevention are also being evaluated. When the first generation of products proved unsuccessful, the field shifted its focus to higher potency, ARV-based candidates, with the assumption that – once something is found to work against HIV – it can become the basis for combination products that also offer contraceptive and/or broader-spectrum STI-prevention benefits.


  1. Global Campaign for Microbicides Frequently Asked Questions About Microbicides. GCM, Washington DC, 2010
  2. HIV Vaccine and Microbicides Resource Tracking Working group Adapting to Realities: Trends in HIV Prevention Research Funding 2000-2008. AIDS Vaccines Advocacy Coalition, New York, 2009
  3. Shattock R State of the ART for microbicides. 2010 International Microbicides Conference, Pittsburgh, presentation #1, opening plenary, 2010
  4. Global Campaign for Microbicides Financing. GCM, Washington DC (http://www.global-campaign.org/economics.htm), accessed 21 February 2011
  5. Gray RT, Wilson DP Anal sex need not be highly prevalent to affect HIV incidence among heterosexual populations. Sex Transm Infect. e-letter (http://sti.bmj.com/letters), published online 22 October 2009
  6. Van Damme L et al. Effectiveness of COL-1492, a nonoxynol-9 vaginal gel, on HIV-1 transmission in female sex workers: a randomised controlled trial. Lancet 360:971-977, 2002
  7. Ramjee G et al. The Acceptability of a Vaginal Microbicide Among South African Men. International Family Planning Perspectives 27(4):167-170, 2001
  8. Mantell JE et al. Microbicide acceptability research: current approaches and future directions. Social Science and Medicine 60(2):319-330, 2005
  9. Schwartz D The Jelly Revolution POZ, issue 57 , March 2007


Written by: Anna Forbes

This content was checked for accuracy at the time it was written. It may have been superseded by more recent developments. NAM recommends checking whether this is the most current information when making decisions that may affect your health.
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