title: Implications of T-cell P-glycoprotein activity during HIV-1 infection and its therapy.
abstract: OBJECTIVE
  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 DiOC2(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.
authors.affiliation: Department of Medicine, Vanderbilt Medical School, Nashville, TN 37203, USA.
authors.forename: Todd
authors.initials: T
authors.lastname: Hulgan
authors.forename: John P
authors.initials: JP
authors.lastname: Donahue
authors.forename: Charlene
authors.initials: C
authors.lastname: Hawkins
authors.forename: Derya
authors.initials: D
authors.lastname: Unutmaz
authors.forename: Richard T
authors.initials: RT
authors.lastname: D'Aquila
authors.forename: Stephen
authors.initials: S
authors.lastname: Raffanti
authors.forename: Fred
authors.initials: F
authors.lastname: Nicotera
authors.forename: Peter
authors.initials: P
authors.lastname: Rebeiro
authors.forename: Husamettin
authors.initials: H
authors.lastname: Erdem
authors.forename: Melissa
authors.initials: M
authors.lastname: Rueff
authors.forename: David W
authors.initials: DW
authors.lastname: Haas
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000097:blood* / Q000235:genetics; D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy / Q000276:immunology*; D000328:Adult; D018791:CD4 Lymphocyte Count; D024882:Drug Resistance, Viral; D005260:Female; D015497:HIV-1; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012367:RNA, Viral / Q000097:blood; D013601:T-Lymphocytes / Q000737:chemistry*
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D012367:RNA, Viral