Antiretroviral microbicides enter clinical trials
[CAPE TOWN] 'Next generation' microbicides containing antiretroviral drugs (ARVs) are in early clinical testing and may hold out the best hope of protecting women from HIV/AIDS, a conference has heard.
Previous trials of nonspecific microbicides — gels containing general antimicrobial agents — have been disappointing, say researchers, with only one product, PRO 2000, still under development (see Microbicide hope at last, say researchers). Results of a phase III trial of PRO 2000 are expected later this year.
Vaginal gels or rings containing HIV-targeting drugs are entering phase I and II trials coordinated by the International Partnership for Microbicides (IPM) and the Microbicide Trials Network (MTN), a non-profit collaboration between developed- and developing-world researchers that is funded by the US National Institutes of Health.
These topical ARVs are intended to inhibit HIV infection by blocking the virus from replicating in the cells it initially infects. Gels would need to be applied before sex, but a vaginal ring could provide protection from unanticipated sex.
Zeda Rosenberg, the IPM's chief executive, told a press conference at the 5th International AIDS Society (IAS) conference in Cape Town, South Africa, this week (21 July) that the trials are investigating how acceptable the different approaches are, as well as their effectiveness.
"Ideally we can develop several effective formulations — gels, tablets or rings — so that women can choose," she said.
MTN's large-scale, five-arm VOICE study will compare a gel containing the antiretroviral tenofovir with a placebo gel, tenofovir tablets, tablets containing both tenofovir and emtricitabine, another antiretroviral and placebo tablets for HIV prevention in southern African women. Recruitment of 5,000 women began this month (July).
Other MTN trials cover rectal tenofovir gels for men and women, and the safety of tenofovir gels in pregnant women. An IPM phase I/II safety trial of gel containing the antiretroviral dapirivine is also in progress.
Women recruited to the trials receive counselling on safe sexual practices and a supply of condoms. Participants who acquire HIV during the trials are offered treatment and are invited to enrol in MTN0015, a long-term observational study.
Most women who take part in the trials say they find them empowering. Women are finding it easier to communicate within relationships about safe sex and condom use after entering the trials," says Sheena McCormack, a clinical epidemiologist at the UK Medical Research Council's Microbicides Development Programme who is involved in PRO 2000 trials.
A marketable microbicide is still several years away, however, as further trials of efficacy and safety are needed. The trials must also address concerns that HIV may become resistant to these drugs.