Systemic preexposure prophylaxis for human immunodeficiency virus infection.

Antiretroviral therapy has significantly improved the typical course of human immunodeficiency virus (HIV) infection in industrialized nations, and life expectancies associated with the infection have increased. However, infection rates have generally remained unchanged, with increases noted among certain subpopulations. The use of systemic preexposure prophylaxis for HIV infection has been proposed as an intervention to reduce the risk of disease transmission in at-risk individuals. The basis of this prophylaxis involves the orchestrated use of antiretrovirals in uninfected individuals either continuously or just before high-risk situations, such as perinatal and occupational exposure to HIV, in order to reduce the likelihood of successful HIV infection. Data from the use of antiretrovirals to prevent HIV infection in these scenarios support the concept of preexposure prophylaxis. Preliminary animal studies have focused on the use of antiretrovirals to prevent simian immunodeficiency virus infection in macaque monkeys, and these data have provided support for the potential efficacy of preexposure prophylaxis for HIV in humans. Limited human data are available, however, but studies are ongoing. Clinical trials have focused on the use of tenofovir disoproxil fumarate either alone or in combination with emtricitabine. Tenofovir-emtricitabine-based regimens may be ideal, given the drugs' pharmacodynamic and pharmacokinetic properties. Some investigators have surveyed at-risk individuals to assess their knowledge of preexposure prophylaxis and whether they used or intended to use this prevention strategy. Routine use of preexposure prophylaxis and even knowledge of its existence appear to be very limited. If efficacy is proved, use of preexposure prophylaxis faces several ethical issues. Ultimately, its success will depend on proof of cost-effectiveness. Until the many questions concerning optimal use of preexposure prophylaxis for HIV are answered, however, its use should be limited to research-related clinical investigations.