Background:  There are 3 ways ART might be used to prevent the sexual transmission of HIV:  as pre-exposure prophylaxis (PREP), as post-exposure prophylaxis (PEP), and as treatment for infected subjects in sexual relationships. Extensive experiments with rhesus macaques support the potential efficacy of PEP and PREP. However, no relevant clinical trials have been completed in humans. PREP trials with the drug tenofovir are ongoing, but several have been delayed by a series of ethical and biological concerns. No PEP trials are planned. In addition, PEP failures have been demonstrated, which may reflect delayed initiation of therapy, less than perfect patient adherence, and rectal exposure to HIV, a particularly efficient route of transmission. ART used as therapy for infected subjects has the potential to prevent sexual transmission of HIV, as demonstrated so clearly in studies of vertical HIV transmission. ART reliably reduces excretion of HIV in male and female genital secretions, and some (but not all) drugs concentrate in semen or in female genital secretions. Two retrospective studies of discordant couples have suggested that ART resulted in reduced HIV transmission, and 2 recent epidemiologic studies have drawn similar conclusions. However, the large number of untreated patients who harbor HIV resistant variants suggests that ART may fail to suppress transmission.

Methods:  To further explore this question, a randomized clinical trial focused on HIV discordant couples (NIH HPTN052) has successfully entered a pilot phase.

Results:  However, “ART as prevention” will be limited by inability to reach people with acute or established infection who are unaware of their status. In addition, while recent evidence suggests that people with acute HIV infection may be particularly contagious, it is not clear that such people will derive personal benefit from ART. Lastly, a substantial number of patients with HIV who are receiving ART may acquire classical sexually transmitted diseases, which can stimulate “break-through” viremia in the genital tract excretions, rendering treated subjects contagious. 

Conclusions:  These concerns notwithstanding, the public health opportunities for ART as prevention are substantial, and ongoing research is likely to improve this important application.