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

TitleOral cyclosporin A inhibits CD4 T cell P-glycoprotein activity in HIV-infected adults initiating treatment with nucleoside reverse transcriptase inhibitors.
Publication TypeJournal Article
Year of Publication2009
AuthorsHulgan T, Donahue JP, Smeaton L, Pu M, Wang H, Lederman MM, Smith K, Valdez H, Pilcher C, Haas DW
Corporate AuthorsAIDS Clinical Trials Group Study A5138 Team
JournalEur J Clin Pharmacol
Volume65
Issue11
Pagination1081-8
Date Published2009 Nov
ISSN1432-1041
KeywordsAdult, 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.

DOI10.1007/s00228-009-0725-5
Alternate JournalEur. J. Clin. Pharmacol.
PubMed ID19779705
PubMed Central IDPMC2873632
Grant ListAI069439 / 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