Oral Cyclosporin A Inhibits CD4 T Cell P-glycoprotein Activity in HIV-infected Adults Initiating Treatment With Nucleoside Reverse Transcriptase Inhibitors

Eur J Clin Pharmacol. 2009 Nov;65(11):1081-8. doi: 10.1007/s00228-009-0725-5.


Purpose: P-glycoprotein limits the tissue penetration of many antiretroviral drugs. The aim of our study was to characterize the effects of the P-glycoprotein substrate cyclosporin A on T cell P-glycoprotein activity in human immunodeficiency virus-infected participants in the AIDS Clinical Trials Group study A5138.

Methods: We studied P-glycoprotein activity on CD4 and CD8 T cells in 16 participants randomized to receive oral cyclosporin A (n=9) or not (n=7) during initiation antiretroviral therapy (ART) that did not include protease or non-nucleoside reverse transcriptase inhibitors.

Results: CD4 T cell P-glycoprotein activity decreased by a median of 8 percentage points with cyclosporin A/ART (difference between cyclosporin A/ART vs. ART only, P= 0.001). Plasma trough cyclosporin A concentrations correlated with the change in P-glycoprotein activity in several T cell subsets.

Conclusions: Oral cyclosporin A can inhibit peripheral blood CD4 T cell P-glycoprotein activity. Targeted P-glycoprotein inhibition may enhance the delivery of ART to T cells.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / antagonists & inhibitors*
  • Adult
  • Anti-HIV Agents / pharmacokinetics
  • Anti-HIV Agents / therapeutic use
  • Antiretroviral Therapy, Highly Active*
  • CD4-Positive T-Lymphocytes / drug effects*
  • CD4-Positive T-Lymphocytes / enzymology
  • CD8-Positive T-Lymphocytes / drug effects
  • CD8-Positive T-Lymphocytes / enzymology
  • Cyclosporine / blood
  • Cyclosporine / pharmacology
  • Cyclosporine / therapeutic use*
  • Enzyme Inhibitors / blood
  • Enzyme Inhibitors / pharmacology
  • Enzyme Inhibitors / therapeutic use*
  • Female
  • Flow Cytometry
  • HIV Infections / drug therapy*
  • Humans
  • Male
  • Middle Aged
  • Young Adult


  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Anti-HIV Agents
  • Enzyme Inhibitors
  • Cyclosporine

Grant support