Narrative review: Antiretroviral therapy to prevent the sexual transmission of HIV-1

Antiretroviral therapy (ART) has prolonged and improved the lives of persons infected with HIV. Theoretically, it can also be used to prevent the transmission of HIV. The pharmacology of ART in the male and female genital tract can be expected to affect the success of the intervention, and ART agents differ considerably in their ability to concentrate in genital tract secretions. Emergency ART is considered to be the standard of care after occupational exposures to fluids or tissues infected with HIV. More recently, ART for prophylaxis after nonoccupational HIV exposures has been widely used and most countries have developed specific guidelines for its implementation. However, developing clinical trials to prove the efficacy of ART postexposure prophylaxis has not been possible. Experiments with rhesus macaques suggest that therapy must be offered as soon as possible after exposure (within 72 hours) and must be continued for 28 days. Additional nonhuman primate experiments have demonstrated protection from HIV infection with ART preexposure prophylaxis, and several clinical trials are under way to evaluate the safety and efficacy of this approach. The degree to which ART offered to infected persons reduces infectiousness is of considerable public health importance, but the question has not been sufficiently answered. This article provides a review of the data on the use of ART to prevent the sexual transmission of HIV and identify challenges to improving and clarifying this approach.