ARV-based HIV microbicides advanced by ground-breaking partnership

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The International Partnership for Microbicides (IPM) has made a far-reaching agreement with Tibotec Pharmaceuticals, a Belgian subsidiary of Johnson & Johnson, to develop an antiretroviral drug as a microbicide to prevent HIV. The agreement was warmly welcomed by UK International Development Secretary Hilary Benn, speaking on Monday at the Microbicides 2004 conference in London.

Johnson & Johnson is the first major pharmaceutical company that has backed microbicide development, although its initial contribution is as much a donation, in the public interest, as a commercial investment. If the project succeeds, a microbicide could be on the market in the USA and Europe in six to ten years’ time, with Johnson & Johnson behind it. However, the greatest need for such products is in developing countries, in Africa, Asia, the Caribbean and Latin America. The British government is one of several in Europe that support IPM, along with the Rockefeller and Bill and Melinda Gates Foundations, UNAIDS, UNFPA, and other funders.

The drug is TMC 120 (dapivirine), a “second generation" non-nucleoside reverse transcriptase inhibitor (NNRTI) active against virus strains resistant to nevirapine and efavirenz. TMC 120 has been abandoned as a treatment drug in favour of the related TMC 125, on account of the poor oral absorption of TMC 120. TMC 120 is an attractive candidate microbicide because it is cheap to make and is chemically stable. It binds tightly to the reverse transcriptase enzyme so it can inactivate free virus as well as virus inside cells. In animal models, TMC 120 is highly protective when used as a microbicidal gel. Phase I clinical trials in female volunteers have already been sponsored by Tibotec in Belgium, with no evidence of adverse effects.



A product (such as a gel or cream) that is being tested in HIV prevention research. It could be applied topically to genital surfaces to prevent or reduce the transmission of HIV during sexual intercourse. Microbicides might also take other forms, including films, suppositories, and slow-releasing sponges or vaginal rings.

reverse transcriptase

A retroviral enzyme which converts genetic material from RNA into DNA, an essential step in the lifecycle of HIV. Several classes of anti-HIV drugs interfere with this stage of HIV’s life cycle: nucleoside reverse transcriptase inhibitors and nucleotide reverse transcriptase inhibitors (NRTIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs). 

drug resistance

A drug-resistant HIV strain is one which is less susceptible to the effects of one or more anti-HIV drugs because of an accumulation of HIV mutations in its genotype. Resistance can be the result of a poor adherence to treatment or of transmission of an already resistant virus.


The process (or rate) of a drug or other substances, such as food, entering the blood.

vaginal ring

A device that is worn inside the vagina for a month at a time, which women can insert and remove themselves. A vaginal ring for HIV prevention that slowly releases the antiretroviral drug dapivirine is being developed.

IPM has been given the right to develop TMC 120 as a microbicide, whether on its own or in combination with any other product. In addition to using it as a gel, IPM plans to explore the possibility of including TMC 120 in a slow-release vaginal ring, which could be inserted in the vagina and left in place for weeks or months. IPM will run clinical trials and work with the World Bank and other international development agencies to make any successful product available to the women who most need it. Johnson & Johnson will retain some rights in relation to the USA and other developed countries, but would pay royalties on all sales to IPM. That money could then be used to expand access or fund new trials of other products.

Clearly, one of the issues that IPM will be confronting throughout its planned research programme is the risk of inducing drug resistance when HIV-positive people are exposed to microbicides. HIV requires at least two mutations to become resistant to TMC 120, which may mean this is less of a problem than it was in the case of nevirapine used to prevent mother-to-child transmission. In principle, it would be given to HIV-negative women, although it would be impossible to guarantee that positive women would not be exposed.

Dr Mark Mitchnick, who heads research and development for IPM, told aidsmap that studies will be undertaken, which are likely to recruit HIV-positive women in the first instance, to assess the extent of the drug resistance risk. Most of the potential exposure should be of HIV-positive men who have intercourse with HIV-negative women using the product. Such exposure is likely to be at a very low level, and may cause no problems at all.

Other ARVs which are being developed as potential microbicides include an NNRTI called UC781, from Biosyn, and the nucleotide analogue reverse transcriptase inhibitor PMPA, a form of tenofovir. Both of these have been shown to protect animals against retrovirus transmission; and initial clinical safety studies have also been undertaken. A study by Susan Schader-Plesman using human cell- and cervical tissue cultures at St George’s Hospital, London, has found that PMPA is synergistic when combined with either TMC 120 or UC 781, which could mean lower doses and cheaper products, or higher efficacy, in real products. Using combinations of ARVs in microbicides might also, of course, help minimise the risks of drug resistance.

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Schader-Plesman S et al. PMPA-NNRTI combination studies demonstrate potent synergism against HIV-1 infection in vitro Microbicides 2004, London, poster 02442.