Antiretroviral Penetration across Three Preclinical Animal Models and Humans in Eight Putative HIV Viral Reservoirs

Antimicrob Agents Chemother. 2019 Dec 20;64(1):e01639-19. doi: 10.1128/AAC.01639-19. Print 2019 Dec 20.

Abstract

For HIV cure strategies like "kick and kill" to succeed, antiretroviral (ARV) drugs must reach effective concentrations in putative viral reservoirs. We characterize penetration of six ARVs in three preclinical animal models and humans. We found that standard dosing strategies in preclinical species closely mimicked tissue concentrations in humans for some, but not all, ARVs. These results have implications for interpreting HIV treatment, prevention, or cure interventions between preclinical and clinical models.

Keywords: HIV; antiretrovirals; pharmacokinetics; species differences; tissue reservoirs.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Anti-HIV Agents / therapeutic use
  • Anti-Retroviral Agents / therapeutic use*
  • Atazanavir Sulfate / therapeutic use
  • Emtricitabine / therapeutic use
  • Female
  • HIV Infections / drug therapy*
  • Humans
  • In Vitro Techniques
  • Maraviroc / therapeutic use
  • Mice
  • Raltegravir Potassium / therapeutic use
  • Tenofovir / therapeutic use

Substances

  • Anti-HIV Agents
  • Anti-Retroviral Agents
  • Raltegravir Potassium
  • Atazanavir Sulfate
  • Tenofovir
  • Emtricitabine
  • Maraviroc