Interactions between tenofovir and nevirapine in CD4+ T cells and monocyte-derived macrophages restrict their intracellular accumulation

J Antimicrob Chemother. 2013 Nov;68(11):2545-9. doi: 10.1093/jac/dkt225. Epub 2013 Jun 21.

Abstract

Objectives: There is no pharmacokinetic interaction between tenofovir and nevirapine, but a higher emergence rate of resistance mutations has been reported when these drugs are coadministered. We sought to examine if there is a potential intracellular interaction that may account for the emergence of resistant virus.

Methods: Primary CD4+ and CD14+ cells were isolated from healthy volunteer blood. Monocyte-derived macrophages were differentiated from CD14+ cells. Accumulation of radiolabelled tenofovir and nevirapine was then assessed in these cells.

Results: We show here that tenofovir and nevirapine immune cell intracellular concentrations are lower when coincubated in CD4+ cells and monocyte-derived macrophages, but not in CD14+ cells.

Conclusions: These data indicate a potential intracellular drug-drug interaction between these drugs that warrants further investigation.

Keywords: HIV; drug–drug interactions; influx drug transporters.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenine / analogs & derivatives*
  • Adenine / pharmacokinetics
  • Anti-HIV Agents / pharmacokinetics*
  • Blood Donors
  • CD4-Positive T-Lymphocytes / metabolism*
  • Cells, Cultured
  • Drug Interactions*
  • Healthy Volunteers
  • Humans
  • Macrophages / metabolism*
  • Nevirapine / pharmacokinetics*
  • Organophosphonates / pharmacokinetics*
  • Tenofovir

Substances

  • Anti-HIV Agents
  • Organophosphonates
  • Nevirapine
  • Tenofovir
  • Adenine