Long-Acting Cabotegravir Protects Macaques Against Repeated Penile Simian-Human Immunodeficiency Virus Exposures

J Infect Dis. 2020 Jul 6;222(3):391-395. doi: 10.1093/infdis/jiaa095.

Abstract

We used a novel penile simian-human immunodeficiency virus (SHIV) transmission model to investigate whether long-acting cabotegravir (CAB LA) prevents penile SHIV acquisition in macaques. Twenty-two macaques were exposed to SHIV via the foreskin and urethra once weekly for 12 weeks. Of these, 6 received human-equivalent doses of CAB LA, 6 received oral emtricitabine/tenofovir disoproxil fumarate, and 10 were untreated. The efficacy of CAB LA was high (94.4%; 95% confidence interval, 58.2%-99.3%) and similar to that seen with oral emtricitabine/tenofovir disoproxil fumarate (94.0%; 55.1%-99.2%). The high efficacy of CAB LA in the penile transmission model supports extending the clinical advancement of CAB LA preexposure prophylaxis to heterosexual men.

Keywords: long-acting HIV PrEP; penile pharmacokinetics; penile transmission macaque model; repeat-challenge.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Chemoprevention / methods
  • Disease Models, Animal
  • Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination / therapeutic use
  • HIV Integrase Inhibitors / administration & dosage*
  • HIV Integrase Inhibitors / pharmacokinetics
  • Macaca mulatta
  • Male
  • Penis / virology
  • Pre-Exposure Prophylaxis
  • Pyridones / administration & dosage*
  • Pyridones / pharmacokinetics
  • Simian Acquired Immunodeficiency Syndrome / prevention & control*
  • Simian Acquired Immunodeficiency Syndrome / transmission*
  • Simian Immunodeficiency Virus / drug effects*
  • Simian Immunodeficiency Virus / metabolism

Substances

  • Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination
  • HIV Integrase Inhibitors
  • Pyridones
  • cabotegravir