Implications of T-cell P-glycoprotein activity during HIV-1 infection and its therapy

Todd Hulgan, John P. Donahue, Charlene Hawkins, Derya Unutmaz, Richard T. D'Aquila, Stephen Raffanti, Fred Nicotera, Peter Rebeiro, Husamettin Erdem, Melissa Rueff, David W. Haas*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

Objectives: P-glycoprotein (P-gp) may reduce antiretroviral efficacy by decreasing disposition of HIV-1 protease inhibitors into tissues and cells. In contrast, P-gp overexpression in vitro can inhibit HIV-1 replication, and some drugs induce P-gp expression. To explore which of these mechanisms predominate in vivo, this study characterized relationships between T-cell P-gp activity and clinical parameters in HIV-infected adults. Methods: P-gp activity was quantified in total and naive CD4+ and CD8+ T cells of HIV-infected adults by flow cytometry using the substrate dye DiOC 2(3). Demographic, virologic, immunologic, and treatment factors were obtained from medical records. Factors associated with P-gp activity were identified using multivariate linear regression. Results: A total of 185 subjects (22% female; 34% African American) were studied, of whom 131 (71%) were receiving antiretroviral treatment. There was marked interindividual variability in P-gp activity. By multivariate analysis, higher CD4+ T-cell P-gp activity was associated with lower log10 HIV-1 RNA (P = 0.005), but not treatment or demographic factors. P-gp activity was correlated across T-cell subsets. Conclusions: The inverse relationship between P-gp activity and plasma HIV-1 RNA is most consistent with an inhibitory effect on viral replication rather than drug disposition. Antiretroviral drug class did not independently predict P-gp activity.

Original languageEnglish (US)
Pages (from-to)119-126
Number of pages8
JournalJournal of Acquired Immune Deficiency Syndromes
Volume34
Issue number2
DOIs
StatePublished - Oct 1 2003

Keywords

  • HIV-1 protease inhibitors
  • Membrane glycoproteins
  • Multiple drug resistance
  • T-lymphocyte subsets

ASJC Scopus subject areas

  • Infectious Diseases
  • Pharmacology (medical)

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