title: Cabotegravir long-acting for HIV-1 prevention.
abstract: OBJECTIVE
  Preexposure prophylaxis (PrEP) with daily Truvada has demonstrated clinical efficacy against HIV-1 acquisition that correlates with high adherence. Long-acting antiretroviral drugs offer an alternative to daily regimens and may improve PrEP adherence. This review summarizes the preclinical nonhuman primate studies for evaluating the efficacy of cabotegravir long-acting as PrEP and the ongoing phase 2a studies assessing safety, tolerability, and acceptability of cabotegravir long-acting.
  
  
  RESULTS
  Cabotegravir is an HIV-1 integrase strand transfer inhibitor with intrinsic properties that permit its formulation as a long-acting injectable suspension. In clinical evaluation, cabotegravir long-acting has a half-life that permits infrequent dosing, possibly once every 3 months. In validated macaque models, cabotegravir long-acting demonstrated high protection against both rectal and vaginal transmission at clinically achievable drug concentrations.
  
  
  CONCLUSIONS
  PrEP, after approval of Truvada, continues to evolve to address adherence limitations of daily dosing. As a long-acting injectable antiretroviral drug, cabotegravir long-acting permits quarterly dosing and demonstrated high efficacy in macaque models supporting dose selection and clinical development. Clinical studies have confirmed dose selection in phase 2a trials with cabotegravir long-acting to ultimately lead to phase 2b/3 PrEP efficacy trials.
authors.affiliation: aAaron Diamond AIDS Research Center, The Rockefeller University, New York, New York bLaboratory Branch, Division of HIV/AIDS Prevention, National Center for HIV, Hepatitis, STD, and Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
authors.forename: Chasity D
authors.initials: CD
authors.lastname: Andrews
authors.forename: Walid
authors.initials: W
authors.lastname: Heneine
mesh_terms: D000818:Animals; D019380:Anti-HIV Agents / Q000008:administration & dosage*; D015658:HIV Infections / Q000188:drug therapy / Q000517:prevention & control*; D015497:HIV-1; D006801:Humans; D008253:Macaca mulatta; D065129:Pre-Exposure Prophylaxis; D011728:Pyridones / Q000008:administration & dosage*; D054659:Diketopiperazines
chemical_list: D019380:Anti-HIV Agents; D011728:Pyridones; C584914:cabotegravir; D054659:Diketopiperazines