Article: Implications of T-cell P-glycoprotein activity during HIV-1 infection and its therapy.
Journal of acquired immune deficiency syndromes (1999)
2003 Volume 34, Issue 2, Page(s) 119–126
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 ...
| 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 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. |
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| MeSH term(s) | ATP Binding Cassette Transporter, Subfamily B, Member 1/blood ; ATP Binding Cassette Transporter, Subfamily B, Member 1/genetics ; Acquired Immunodeficiency Syndrome/drug therapy ; Acquired Immunodeficiency Syndrome/immunology ; Adult ; CD4 Lymphocyte Count ; Drug Resistance, Viral ; Female ; HIV-1 ; Humans ; Male ; Middle Aged ; Polymorphism, Genetic ; RNA, Viral/blood ; T-Lymphocytes/chemistry |
| Chemical Substances | ATP Binding Cassette Transporter, Subfamily B, Member 1 ; RNA, Viral |
| Language | English |
| Publishing date | 2003-10-02 |
| Publishing country | United States |
| Document type | Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, P.H.S. |
| ZDB-ID | 645053-2 |
| ISSN | 1944-7884 ; 1077-9450 ; 1525-4135 ; 0897-5965 ; 0894-9255 |
| ISSN (online) | 1944-7884 ; 1077-9450 |
| ISSN | 1525-4135 ; 0897-5965 ; 0894-9255 |
| DOI | 10.1097/00126334-200310010-00001 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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