title: HIV prevention by oral preexposure prophylaxis.
abstract: The impressive advances in antiretroviral (ARV) therapy of chronic human immunodeficiency virus (HIV) infections during the last decade and the availability of potent ARV drugs have fueled interest in using chemoprophylaxis as a novel HIV prevention strategy. Preexposure prophylaxis (PrEP) refers to the use of ARV drugs in HIV-negative persons to prevent HIV infection. The rationale for PrEP builds on the success of ARV prophylaxis in preventing mother-to-child transmission of HIV and on a large body of animal studies that show the efficacy of PrEP against mucosal and parenteral infection. We focus on oral administration of ARV drugs for prevention of HIV infection. Identifying an effective prophylactic pill that individuals can take outside the setting of sexual intercourse precludes the necessity to disclose such use to their partners, thereby empowering those who might not be in a position to negotiate with their partners. Several human clinical trials evaluating the efficacy of daily regimens of the HIV reverse-transcriptase (RT) inhibitors tenofovir disoproxil fumarate (TDF) or Truvada (TDF and emtricitabine [FTC]) are under way among high-risk populations. The results of one trial among men who have sex with men showed that daily Truvada was safe and effective, providing the first support for oral PrEP as a prevention strategy. Here we outline the preclinical and clinical research on oral PrEP, pharmacologic considerations, and future directions and challenges.
authors.affiliation: Laboratory Branch, Division of HIV/AIDS Prevention, National Center for HIV, Hepatitis, STD, and Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia 30333, USA. wheneine@cdc.gov
authors.forename: Walid
authors.initials: W
authors.lastname: Heneine
authors.forename: Angela
authors.initials: A
authors.lastname: Kashuba
mesh_terms: D000225:Adenine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000493:pharmacokinetics / Q000627:therapeutic use; D000284:Administration, Oral; D000818:Animals; D044966:Anti-Retroviral Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D015658:HIV Infections / Q000517:prevention & control* / Q000635:transmission; D018023:HIV Seronegativity; D006801:Humans; D008297:Male; D009092:Mucous Membrane / Q000378:metabolism; D063065:Organophosphonates / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D011485:Protein Binding; D012007:Rectum / Q000378:metabolism; D000068698:Tenofovir; D014621:Vagina / Q000378:metabolism; D014779:Virus Replication / Q000502:physiology
chemical_list: D044966:Anti-Retroviral Agents; D063065:Organophosphonates; D000068698:Tenofovir; D000225:Adenine