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Innovations in antiretroviral (ARV) treatment strategies have resulted in treated HIV‐infected patients having life expectancies similar to those of uninfected individuals. Yet the number of individuals capable of HIV transmission is increasing—for every person in whom ARV treatment is initiated, four others are becoming newly infected with HIV. The limited progress with microbicides and vaccines for HIV prevention reinforce the need for a concentrated exploration of the utility of ARVs. Preliminary animal studies with topical and systemic ARVs show promising results. However, current clinical trials were designed without a comprehensive understanding of ARV pharmacokinetic–pharmacodynamic relationships in HIV prevention. This review focuses on current strategies for the prevention of HIV infection and on the ways in which the tools of pharmacology can be a valuable resource for determining pharmacodynamic …