Oral cyclosporin A inhibits CD4 T cell P-glycoprotein  activity in HIV-infected adults initiating treatment  with nucleoside reverse transcriptase inhibitors.
OBJECTIVE
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.
Department of Medicine, Division of Infectious Diseases, Vanderbilt University School of Medicine, Nashville, TN 37203, USA. todd.hulgan@vanderbilt.edu
Todd
T
Hulgan
John P
JP
Donahue
Laura
L
Smeaton
Minya
M
Pu
Hongying
H
Wang
Michael M
MM
Lederman
Kimberly
K
Smith
Hernan
H
Valdez
Christopher
C
Pilcher
David W
DW
Haas
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors*; D000328:Adult; D019380:Anti-HIV Agents / Q000493:pharmacokinetics / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000201:enzymology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000201:enzymology; D016572:Cyclosporine / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use*; D004791:Enzyme Inhibitors / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D005434:Flow Cytometry; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D055815:Young Adult
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D019380:Anti-HIV Agents; D004791:Enzyme Inhibitors; D016572:Cyclosporine