HIV antiretroviral postexposure prophylaxis: a cautionary note.

Antiretroviral therapy can be used in 3 ways to prevent the sexual transmission of HIV infection: (1) to reduce an infected person's viral burden below a critical threshold; (2) as preexposure prophylaxis for people with persistent high-risk be-havior(s); and (3) as postexposure pro-phylaxis (PEP) to be used after occupational needlesticks or sexual or other nonoccupational risks [1]. The first 2 approaches are currently being tested in clinical trials to evaluate their efficacy. However , PEP has already found its way into widespread clinical practice. Antiretroviral PEP initiated after occupational needlesticks has been used in an attempt to protect health care workers after exposure to HIV. On the basis of historical data, Cardo et al. [2] used a case-control design and reported that zidovu-dine appeared to reduce the risk of HIV infection by 81%, from ∼1 in 200 to 1 in 10,000. But it has been impossible to design case-control or prospective studies to determine the efficacy of the nonoccu-pational use of PEP against sexual transmission when a partner's HIV infection status is unknown, and given the poor efficiency of the transmission of HIV infection [3]. Data generated in studies of ma-caques suggest that therapy for HIV infection initiated within 72 h after genital tract exposure and continued for 28 days can prevent sexual acquisition of HIV infection in the majority of animals [re-viewed in 4, 5]. These observations (and their limitations) have led to an explosion of articles about occupational and nonoccupational prophylaxis that focus on the feasibility [6–9] and the cost (and benefit) [10] of such prevention. Feasibility studies have generally demonstrated successful application of the idea [11], although in some studies, toxicity [12–15] or poor adherence [16, 17] became a limiting problem. In response to biological plausibility and widespread use, many countries (most recently the United States) have established formal guidelines for the administration of nonoccupational PEP. These guidelines all recommend the earliest possible initiation of therapy (within 72 h after exposure) with multiple drugs for 28 days [18–26]. In this issue of Clinical Infectious Diseases , Roland et al. [27] offer an important cautionary note. They present the results of a study of 702 subjects exposed to HIV (94.6% of whom had sexual exposure) who received antiviral prophylaxis and were followed up for 12 weeks. Seven men (1%) in this study acquired HIV infection despite receiving antiviral treatment, all of whom were exposed to HIV through receptive …