The crosstalk between antiretrovirals pharmacology and HIV drug resistance

Expert Rev Clin Pharmacol. 2020 Jul;13(7):739-760. doi: 10.1080/17512433.2020.1782737. Epub 2020 Jun 30.

Abstract

Introduction: The clinical development of antiretroviral drugs has been followed by a rapid and concomitant development of HIV drug resistance. The development and spread of HIV drug resistance is due on the one hand to the within-host intrinsic HIV evolutionary rate and on the other to the wide use of low genetic barrier antiretrovirals.

Areas covered: We searched PubMed and Embase on 31 January 2020, for studies reporting antiretroviral resistance and pharmacology. In this review, we assessed the molecular target and mechanism of drug resistance development of the different antiretroviral classes focusing on the currently approved antiretroviral drugs. Then, we assessed the main pharmacokinetic/pharmacodynamic of the antiretrovirals. Finally, we retraced the history of antiretroviral treatment and its interconnection with antiretroviral worldwide resistance development both in , and middle-income countries in the perspective of 90-90-90 World Health Organization target.

Expert opinion: Drug resistance development is an invariably evolutionary driven phenomenon, which challenge the 90-90-90 target. In high-income countries, the antiretroviral drug resistance seems to be stable since the last decade. On the contrary, multi-intervention strategies comprehensive of broad availability of high genetic barrier regimens should be implemented in resource-limited setting to curb the rise of drug resistance.

Keywords: HIV; antiretroviral treatment; clinical pharmacology; drug resistance; genotypic resistance.

Publication types

  • Review

MeSH terms

  • Anti-HIV Agents / administration & dosage*
  • Anti-HIV Agents / pharmacokinetics
  • Anti-HIV Agents / pharmacology
  • Drug Development
  • Drug Resistance, Viral
  • HIV Infections / drug therapy*
  • HIV Infections / virology
  • HIV-1 / drug effects
  • HIV-1 / isolation & purification
  • Humans

Substances

  • Anti-HIV Agents