title: Cabotegravir long acting injection protects macaques against intravenous challenge with SIVmac251.
abstract: We evaluated the effectiveness of cabotegravir (CAB; GSK1265744 or GSK744) long acting as preexposure prophylaxis (PrEP) against intravenous simian immunodeficiency virus (SIV) challenge in a model that mimics blood transfusions based on the per-act probability of infection.
  
  
  
  CAB long acting is an integrase strand transfer inhibitor formulated as a 200 mg/ml injectable nanoparticle suspension that is an effective PrEP agent against rectal and vaginal simian/human immunodeficiency virus transmission in macaques.
  
  
  
  Three groups of rhesus macaques (n = 8 per group) were injected intramuscularly with CAB long acting and challenged intravenously with 17 animal infectious dose 50% SIVmac251 on week 2. Group 1 was injected with 50 mg/kg on week 0 and 4 to evaluate the protective efficacy of the CAB long-acting dose used in macaque studies mimicking sexual transmission. Group 2 was injected with 50 mg/kg on week 0 to evaluate the necessity of the second injection of CAB long acting for protection against intravenous challenge. Group 3 was injected with 25 mg/kg on week 0 and 50 mg/kg on week 4 to correlate CAB plasma concentrations at the time of challenge with protection. Five additional macaques remained untreated as controls.
  
  
  
  CAB long acting was highly protective with 21 of the 24 CAB long-acting-treated macaques remaining aviremic, resulting in 88% protection. The plasma CAB concentration at the time of virus challenge appeared to be more important for protection than sustaining therapeutic plasma concentrations with the second CAB long acting injection.
  
  
  
  These results support the clinical investigation of CAB long acting as PrEP in people who inject drugs.
authors.affiliation: aAaron Diamond AIDS Research Center, The Rockefeller University, New York City, New York bViiV Healthcare, Research Triangle Park, North Carolina cTulane National Primate Research Center, Covington, Louisiana dGlaxoSmithKline, Research Triangle Park, North Carolina, USA.
authors.forename: Chasity D
authors.initials: CD
authors.lastname: Andrews
authors.forename: Leslie St
authors.initials: LS
authors.lastname: Bernard
authors.forename: Amanda Yee
authors.initials: AY
authors.lastname: Poon
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Mohri
authors.forename: Natanya
authors.initials: N
authors.lastname: Gettie
authors.forename: William R
authors.initials: WR
authors.lastname: Spreen
authors.forename: Agegnehu
authors.initials: A
authors.lastname: Gettie
authors.forename: Kasi
authors.initials: K
authors.lastname: Russell-Lodrigue
authors.forename: James
authors.initials: J
authors.lastname: Blanchard
authors.forename: Zhi
authors.initials: Z
authors.lastname: Hong
authors.forename: David D
authors.initials: DD
authors.lastname: Ho
authors.forename: Martin
authors.initials: M
authors.lastname: Markowitz
mesh_terms: D000818:Animals; D019380:Anti-HIV Agents / Q000008:administration & dosage*; D003692:Delayed-Action Preparations / Q000008:administration & dosage*; D005260:Female; D007273:Injections, Intramuscular; D008253:Macaca mulatta; D065129:Pre-Exposure Prophylaxis / Q000379:methods*; D011728:Pyridones / Q000008:administration & dosage*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000517:prevention & control*; D016896:Treatment Outcome; D054659:Diketopiperazines
chemical_list: D019380:Anti-HIV Agents; D003692:Delayed-Action Preparations; D011728:Pyridones; C584914:cabotegravir; D054659:Diketopiperazines