Oral cyclosporin A inhibits CD4 T cell P-glycoprotein activity in HIV-infected adults initiating treatment with nucleoside reverse transcriptase inhibitors.

Hulgan T, Donahue JP, Smeaton L, Pu M, Wang H, Lederman MM, Smith K, Valdez H, Pilcher C, Haas DW, AIDS Clinical Trials Group Study A5138 Team
Eur J Clin Pharmacol. 2009 65 (11): 1081-8

PMID: 19779705 · PMCID: PMC2873632 · 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.

MeSH Terms (15)

Adult Anti-HIV Agents Antiretroviral Therapy, Highly Active ATP Binding Cassette Transporter, Subfamily B, Member 1 CD4-Positive T-Lymphocytes CD8-Positive T-Lymphocytes Cyclosporine Enzyme Inhibitors Female Flow Cytometry HIV Infections Humans Male Middle Aged Young Adult

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