Anti-HIV Microbicides could generate drug resistance

Vaginal microbicides containing antiretrovirals to prevent HIV infection in women could lead to many cases of drug resistance, according to research published in the July 15 issue of the Proceedings of the National Academy of Sciences.

David P. Wilson, PhD, of the University of New South Wales in Sydney, Australia, and colleagues used mathematical modeling to assess the potential outcomes of a trial of an antiretroviral-based microbicide, tracking female sex workers at high risk of HIV infection; they also created a model for community heterosexual transmission. Their analyses allowed for the microbicides to be either high-risk for resistance (being systemically absorbed) or low-risk (poorly absorbed).

The investigators found that a high-risk microbicide could create many resistant cases if adherence is high, but if adherence is low, it would only create a few cases. High-risk microbicides could create increased levels of antiretroviral resistance in a population if used in a public health intervention, the authors write. In another finding, either type of microbicide could lead to greater reductions in HIV incidence in men than women.

“Whether this will occur will be determined by (i) the degree to which women adhere to microbicides, (ii) microbicide efficacy, and (iii) the viral fitness of drug-resistant strains. It is paradoxical that men may benefit more than women because of the development of effective microbicides; this paradoxical effect will be exacerbated if high-risk microbicides are used. We predict, therefore, that the population-level consequences of public health interventions that use antiretroviral-based microbicides could well be surprising,” the authors conclude.

Wilson DP, Coplan PM, Wainberg MA, et al. The paradoxical effects of using antiretroviral-based microbicides to control HIV epidemics. Proc Nat Acad Sciences. Published online before print July 7, 2008, doi: 10.1073/pnas.0711813105