Journal Article

Effect of protease inhibitor-containing regimens on lymphocyte multidrug resistance transporter expression

J. Ford, E. R. Meaden, P. G. Hoggard, M. Dalton, P. Newton, I. Williams, S. H. Khoo and D. J. Back

in Journal of Antimicrobial Chemotherapy

Published on behalf of British Society for Antimicrobial Chemotherapy

Volume 52, issue 3, pages 354-358
Published in print September 2003 | ISSN: 0305-7453
Published online September 2003 | e-ISSN: 1460-2091 | DOI: http://dx.doi.org/10.1093/jac/dkg381
Effect of protease inhibitor-containing regimens on lymphocyte multidrug resistance transporter expression

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  • Medical Oncology
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Background: Increased expression of multidrug resistance transporters, such as P-glycoprotein (P-gp), has been suggested as a potential mechanism for decreased protease inhibitor (PI) availability at certain intracellular sites and tissue compartments.

Objectives: To investigate the effect of PIs on the surface lymphocyte expression of P-gp in vitro and in vivo.

Patients and methods: Peripheral blood mononuclear cells (PBMCs) were isolated from healthy subjects (n = 15) and incubated (72 h) with 10 µM of each PI studied (saquinavir, ritonavir, nelfinavir, indinavir, amprenavir and lopinavir), or dimethyl sulphoxide (DMSO) control. PBMCs were also isolated from HIV-infected subjects (n = 50; viral load <50 copies/mL) on a PI- or a non-PI-containing combination antiretroviral regimen. P-gp expression was analysed by flow cytometry.

Results: No differences in surface P-gp expression on lymphocytes, CD4+ or CD8+ lymphocyte subsets were observed following incubation with 10 µM saquinavir, ritonavir, indinavir, amprenavir or lopinavir in vitro. Nelfinavir, however, increased P-gp expression. In vivo, no difference in P-gp expression on total lymphocytes was observed between patients receiving a PI-containing regimen [saquinavir n = 9, ritonavir n = 6, nelfinavir n = 7, indinavir n = 7 and lopinavir/ritonavir n = 13, and two nucleoside reverse transcriptase inhibitors (NRTIs)] and patients receiving a control regimen of three NRTIs alone (n = 8).

Conclusion: This study suggests that, of the PIs, only nelfinavir increases P-gp expression in vitro, and in vivo the PI class of antiretrovirals do not increase P-gp expression on lymphocytes. It is clear that factors other than PI induction are important in the inter-individual variability in the lymphocyte expression of P-gp.

Keywords: Keywords: P-glycoprotein, flow cytometry, HIV, CD4+, CD8+, HAART, multidrug resistance transporters.

Journal Article.  3947 words.  Illustrated.

Subjects: Medical Oncology ; Critical Care

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