Pharmacologic Opportunities for HIV Prevention

Over the past 10 years, innovations in antiretroviral (ARV) treatment strategies have resulted in treated HIV-infected patients having similar life expectancies as their uninfected counterparts.1 Yet the number of individuals capable of HIV transmission is increasing. According to the Joint United Nations Programme on HIV/AIDS (UNAIDS), the number of newly infected individuals worldwide in 2008 was ~2.7 million.2 Since the early 1990s, transmission rates have been relatively stable in the United States.3 This is attributable, in part, to increased efforts in carrying out HIV screening, placing patients into care, and promoting behavior-modifying interventions.4 However, countries that lack access to resources have not had similar success. For example, between 2001 and 2008, in the Middle East and North Africa, the number of newly infected individuals increased by 17%, and the number of adult and child deaths caused by AIDS increased by 80%.2 The World Health Organization estimates that for every person in whom ARV treatment is initiated, four others are newly infected with HIV.5 Because current treatment interventions are not likely to curb the HIV epidemic, other prevention efforts are desperately needed. As illustrated in Figure 1, interventions for HIV prevention can be divided into four main strategies based on the time course of exposure. In an individual who has yet to be exposed to HIV, behavioral and structural interventions may be effective.4 In an exposed individual at the time of coital exposure, a vaccine that provides neutralizing antibodies or a pre-exposure prophylaxis (PrEP) intervention with topical microbicides/ARVs or with systemic ARVs may be effective. In an exposed individual shortly after the time of exposure, a vaccine or a postexposure prophylaxis (PEP) intervention with ARVs may be effective. Once infected, an individual may be rendered less infectious if placed on potent combination ARV therapy.6,7 Figure 1 Opportunities for prevention. PEP, postexposure prophylaxis; PrEP, pre-exposure prophylaxis. The efficacy of each of the aforementioned interventions depends on the type and timing of the intervention. Strategies that reduce transmission risks, such as male circumcision and condom use, along with other behavior-modifying interventions, have shown 50–80% efficacy in clinical trials.8 However, achieving consistent implementation of these practices remains a challenge, particularly given the social and cultural conditions that can preclude women from being empowered to insist that their sexual partners adopt these measures.9 Recent advances in vaccine development are encouraging,10 but worldwide implementation of an effective vaccine is years away. Therefore, it is critical to identify potential pharmacologic interventions to curtail the HIV epidemic quickly. These strategies include the use of microbicides and traditional ARV drugs, either systemically or topically. Typically, microbicides act in the vaginal lumen to either destroy the virus before it can traverse mucosal surfaces or prevent viral attachment to mucosal surfaces. This is in contrast to ARVs, which are distributed into tissues following oral or topical application and act at the mononuclear cellular level to prevent viral entry or replication. This article provides a brief review of the opportunities regarding pharmacologic interventions and their roles in the exposure continuum (Figure 1). We also summarize current obstacles facing the clinical pharmacology of HIV prevention and possible opportunities to overcome them.