With no HIV/AIDS vaccine or cure in sight, vaginal microbicides now in clinical trials are one of the most promising weapons that will protect women against HIV infection. Yet these microbicides could be of more benefit to men than to women, according to a new study co-authored by the University of New South Wales’ National Centre in HIV Epidemiology and Clinical Research (NCHECR) and UCLA.
The study, which used novel mathematical models to simulate clinical trials and population-level transmission, was published in the online issue of the prestigious Proceedings of the National Academy of Sciences.
It follows an announcement by the NSW government of $20 million toward a major new National Institute for Virology, to be led by NCHECR and based at St Vincent’s Hospital in Sydney.
Apart from the study’s findings of an unexpected benefit for men – vaginal microbicides could prevent 27 per cent of infections in men compared to 21 per cent in women – it also raises concern that the microbicides could lead to drug resistance if used by HIV-positive women and that this risk may be masked under current trial designs. This suggests the need for significant caution if the microbicides are licensed to the general public.
The mathematical models were used by a team of international researchers who used epidemiological, clinical and behavioural data to predict outcomes of a 12-month Phase III trial for second-generation microbicides underway in South Africa, Tanzania, Rwanda and Belgium, and involving 10,000 participants.
Microbicides – compounds in the form of gels, creams, films or suppositories that can be applied inside the vagina or rectum to protect against sexually transmitted infections including HIV – potentially give women some control over HIV protection. Condom use is largely dictated by men.
The study’s first author Dr David Wilson, from NCHECR, says great hopes are resting on the current trials.
“The antiretroviral drugs within these microbicides are the same as those used to treat people who are infected with HIV, so there is great expectation that the microbicides will be very effective.
“However this study predicts the potential outcomes of the trials and warns of potential risks that could arise,” he says
“The analysis shows that even if the trials are very successful the products may have undesirable consequences – such as drug resistance – when used in the general public and without monitoring.
Dr Wilson and Professor Sally Blower, senior author of the study from the Medical School at the University of California in Los Angeles, say the problems arise when HIV-positive women who are unaware of their status use the microbicides.
“If microbicides that contain antiretroviral drugs are used by HIV-positive women, the product can potentially ‘force’ the regular wild type virus to become drug resistant,” Dr Wilson says.
“This limits therapeutic options, which is the big concern.”
The likelihood that vaginal microbicides would benefit men more than women was also unforeseen before the trial.
The authors explain that drug resistant strains are less ‘fit’ and it is thought that they are less likely to be sexually transmitted. The consequence is that women will have higher levels of drug resistance and the overall rate of transmission of the virus to men is then reduced – so fewer men will be infected.
Despite these findings, the authors say there is reason for optimism around microbicides.
“These microbicides could be effective and greatly reduce HIV incidence. But in these trials drug resistance should be monitored carefully and also the level of drug absorption should be measured. If the products are made available to the general population in the future then regular monitoring of users should be carried out,” Dr Wilson says.
(Source: Proceedings of the National Academy of Sciences: University of New South Wales: July 2008)