In the July 15, 2008 issue of the Proceedings of the National Academy of Sciences (http://www.pnas.org), Dr. Sally Blower and her colleagues report that mathematical models of real-world use of ARV-based vaginal microbicides predict that men may actually derive greater long-term protection against HIV infection than women. There are a lot of assumptions and unknowns in these models, including questions of microbicide efficacy and adherence, condom use, and drug resistance. But even if ARV-based microbicides turn out to be only partially effective, these models predict that large numbers of at-risk men and women will be protected if these products are widely available and used.

One question that remains unanswered, however, is whether the widespread use of an ARV-based microbicide could select for drug resistant strains of HIV. The women enrolled in current or planned trials of ARV-based candidate microbicides likely are at low risk of developing drug resistance. Trial participants will be screened monthly for HIV infection, and will stop using a candidate microbicide immediately if they become infected. These women will be tested frequently to see if they develop drug-resistant virus, and arrangements will be made to ensure they have access to effective drugs. However, as the Blower model suggests, even if an ARV-based candidate microbicide does not seem to select for drug resistant virus during phase II and phase III safety and effectiveness trials, drug resistance could be a long-term problem once the product is widely available and used by women who undergo much more infrequent HIVcounselling and testing. Thus, it will be important to couple the widespread introduction of ARV-based microbicides with increased counselling, education, HIV testing, and drug resistance monitoring for at-risk individuals.

To learn more about ARV-based microbicides and HIV drug resistance, see the GCM fact sheets entitled “ARV-based Microbicides: The Promise and The Puzzle” and “Understanding HIV Drug Resistance.” These and other basic GCM fact sheets and materials are available for free download at http://www.global-campaign.org/download.htm.