title: Long-acting rilpivirine for HIV prevention.
abstract: OBJECTIVE
  Long-acting injectable antiretroviral (ARV) formulations are being developed for the treatment and prevention of HIV infection. The purpose of this review is to summarize recent preclinical and clinical data on TMC278 (rilpivirine), a nonnucleoside reverse transcriptase inhibitor (NNRTI), that is being developed for both a treatment and prevention indication.
  
  
  RESULTS
  Long-acting rilpivirine has demonstrated efficacy in preventing HIV acquisition in a humanized mouse model and has been found to be well tolerated and acceptable in several Phase I clinical trials. Pharmacokinetic data from Phase I studies suggest that 1200 mg of long-acting rilpivirine administered every 8 weeks would be associated with plasma and tissue levels of rilpivirine anticipated to be necessary for preventing HIV infection. This regimen is being evaluated in the HPTN-076 Phase II expanded safety study that will enroll women in South Africa, Zimbabwe, and the USA. The HPTN-076 study requires a 4-week run in with oral rilpivirine (25 mg capsules) before receiving 1200 mg of rilpivirine. It is not yet certain whether oral dosing will remain a prerequisite in future trials or post licensure.
  
  
  CONCLUSIONS
  Long-acting rilpivirine shows promise as a candidate agent for HIV prevention. Preclinical efficacy has been demonstrated in a murine model. Phase I studies have shown good safety and efficacy, but breakthrough infection and resistance have been documented with lower doses of long-acting rilpivirine. Phase II development for a prevention indication is ongoing.
authors.affiliation: aDepartment of HIV/Genito-Urinary Medicine, St. Stephen's Centre, Chelsea and Westminster Hospital, London, UK bMagee-Womens Research Institute, Division of Gastroenterology, Hepatology, and Nutrition, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
authors.forename: Akil
authors.initials: A
authors.lastname: Jackson
authors.forename: Ian
authors.initials: I
authors.lastname: McGowan
mesh_terms: D000818:Animals; D019380:Anti-HIV Agents / Q000008:administration & dosage*; D017322:Clinical Trials, Phase II as Topic; D003692:Delayed-Action Preparations; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000517:prevention & control*; D006801:Humans; D007273:Injections, Intramuscular; D008297:Male; D053758:Nanoparticles / Q000008:administration & dosage; D065129:Pre-Exposure Prophylaxis; D016032:Randomized Controlled Trials as Topic; D000068696:Rilpivirine / Q000008:administration & dosage*
chemical_list: D019380:Anti-HIV Agents; D003692:Delayed-Action Preparations; D000068696:Rilpivirine