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

Hulgan T, Donahue JP, Hawkins C, Unutmaz D, D'Aquila RT, Raffanti S, Nicotera F, Rebeiro P, Erdem H, Rueff M, Haas DW
J Acquir Immune Defic Syndr. 2003 34 (2): 119-26

PMID: 14526200

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 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.

MeSH Terms (13)

Acquired Immunodeficiency Syndrome Adult ATP Binding Cassette Transporter, Subfamily B, Member 1 CD4 Lymphocyte Count Drug Resistance, Viral Female HIV-1 Humans Male Middle Aged Polymorphism, Genetic RNA, Viral T-Lymphocytes

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