Modeling Microbicides

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Science  25 Jul 2008:
Vol. 321, Issue 5888, pp. 466
DOI: 10.1126/science.321.5888.466a

Phase III clinical trials are underway to test the efficacy of antiretroviral (ARV)-based microbicides in preventing HIV transmission. However, the risk that ARVs may be absorbed systemically and promote the evolution of drug-resistant viral strains if used by HIV-positive women remains poorly characterized.

Wilson et al. have modeled the effects of ARV-based microbicides on disease dynamics, either as part of a clinical trial or as a widespread public health intervention, in order to compare drugs with a high versus low potential risk for generating resistance. They find that a clinical trial will be unable to distinguish between high- and low-risk microbicides if HIV-positive participants are excluded on the basis of monthly tests for seroconversion (as planned for the upcoming dapivirine trial), given that resistance is expected to take at least 6 months on average to develop. If a high-risk microbicide is used as a public health intervention, the model predicts that the ratio of the number of prevented infections to the number of acquired resistant cases (the benefit-to-cost ratio) may not be much greater than 1. The ratio will be worse for women than for men, given that new cases of resistance will emerge in women initially and that drug-resistant strains have lower transmission efficiency than wild-type HIV. These results highlight the importance of collecting additional data on the resistance risks of new ARV-based microbicides before they are approved for popular use. — NM*

Proc. Natl. Acad. Sci. U.S.A. 105, 9835 (2008).

  • * Nilah Monnier is a summer intern in Science's editorial department.

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