Title | Oral cyclosporin A inhibits CD4 T cell P-glycoprotein activity in HIV-infected adults initiating treatment with nucleoside reverse transcriptase inhibitors. |
Publication Type | Journal Article |
Year of Publication | 2009 |
Authors | Hulgan T, Donahue JP, Smeaton L, Pu M, Wang H, Lederman MM, Smith K, Valdez H, Pilcher C, Haas DW |
Corporate Authors | AIDS Clinical Trials Group Study A5138 Team |
Journal | Eur J Clin Pharmacol |
Volume | 65 |
Issue | 11 |
Pagination | 1081-8 |
Date Published | 2009 Nov |
ISSN | 1432-1041 |
Keywords | Adult, Anti-HIV Agents, Antiretroviral Therapy, Highly Active, CD4-Positive T-Lymphocytes, CD8-Positive T-Lymphocytes, Cyclosporine, Enzyme Inhibitors, Female, Flow Cytometry, HIV Infections, Humans, Male, Middle Aged, P-Glycoprotein, Young Adult |
Abstract | 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. |
DOI | 10.1007/s00228-009-0725-5 |
Alternate Journal | Eur. J. Clin. Pharmacol. |
PubMed ID | 19779705 |
PubMed Central ID | PMC2873632 |
Grant List | AI069439 / AI / NIAID NIH HHS / United States AI25879 / AI / NIAID NIH HHS / United States AI36219 / AI / NIAID NIH HHS / United States AI38855 / AI / NIAID NIH HHS / United States AI50410 / AI / NIAID NIH HHS / United States AI54999 / AI / NIAID NIH HHS / United States AI68636 / AI / NIAID NIH HHS / United States AI69423 / AI / NIAID NIH HHS / United States K12 RR017697 / RR / NCRR NIH HHS / United States K12 RR017697-05 / RR / NCRR NIH HHS / United States K12 RR17697 / RR / NCRR NIH HHS / United States K23 AT002508 / AT / NCCIH NIH HHS / United States K23 AT002508-04 / AT / NCCIH NIH HHS / United States K23 AT02508 / AT / NCCIH NIH HHS / United States MH071205 / MH / NIMH NIH HHS / United States P30 AI036219 / AI / NIAID NIH HHS / United States P30 AI036219-15S1 / AI / NIAID NIH HHS / United States P30 AI050410 / AI / NIAID NIH HHS / United States P30 AI050410-11 / AI / NIAID NIH HHS / United States P30 AI054999 / AI / NIAID NIH HHS / United States P30 AI054999-05 / AI / NIAID NIH HHS / United States R01 MH071205 / MH / NIMH NIH HHS / United States R01 MH071205-05 / MH / NIMH NIH HHS / United States U01 AI025879 / AI / NIAID NIH HHS / United States U01 AI025879-13 / AI / NIAID NIH HHS / United States U01 AI038855 / AI / NIAID NIH HHS / United States U01 AI038855-09S2 / AI / NIAID NIH HHS / United States U01 AI068636 / AI / NIAID NIH HHS / United States U01 AI068636-04S1 / AI / NIAID NIH HHS / United States U01 AI069423 / AI / NIAID NIH HHS / United States U01 AI069423-04 / AI / NIAID NIH HHS / United States U01 AI069439 / AI / NIAID NIH HHS / United States U01 AI069439-04 / AI / NIAID NIH HHS / United States |