7th Annual Conference Of The British HIV Association [BHIVA] 27 – 29 April 2001, The Hove Centre, Brighton

[AUTHOR(S):] M Hennessy¹, K Motumise¹, FM Mulcahy², S Clarke², C Bergin², D Kelleher³, J Feely¹, M Barry^1
1 Department of Clinical Pharmacology and Therapeutics, ² GUIDE Clinic, and ³ Department of Molecular Medicine, St James' Hospital, Dublin, Ireland

BHIVA Conf 2001 Apr 27-29;7:O16

INTRODUCTION: P-gp is a transmembrane efflux pump for antiretroviral agents, in addition, HIV virus production is decreased in multidrug resistant cell lines in vitro. We explored the effect of HIV disease on P-gp expression and function in peripheral blood lymphocytes (PBLs) of HIV infected patients (n=71) and healthy controls (n=24). PBLs were isolated, fixed, permeabilised, stained (P-gp specific antibody) and quantified by flow cytometry. The MDR1 gene product was confirmed by reverse transcriptase polymerase chain reaction P-gp function was determined by rhodamine efflux and expressed as a ratio. Ritonavir was used to assess inhibition of P-gp function.

RESULTS: P-gp expression was reduced (P<0.05) in the PBLs of treatment-naïve HIV-infected patients (3.5±0.53 MFI) compared with controls (6.3±0.43 MFI). Expression was similar in patients successfully treated with highly active antiretroviral therapy (HAART) (7.97±0.58 MFI) compared with controls, but remained reduced (P<0.05) in patients unsuppressed despite HAART (2.96±0.86 MFI). P-gp expression correlated with viral load (P<0.05) independently of disease stage or CD4 count. P-gp-mediated rhodamine efflux was reduced (P<0.05) in untreated (0.41±0.15) and treated unsuppressed patients (0.37±0.07) compared with controls (0.17±0.04). Ritonavir inhibited P–gp function in PBLs from untreated (81.2±7.3%) and treated suppressed (61.7±6.6%) and treated unsuppressed (57.3±10%) patients.

CONCLUSION: P-gp expression in HIV patients is inversely related to viral load independently of disease stage or treatment. P-gp was functional in all groups and inhibited by ritonavir. In vivo, P-gp appears important for immune reconstitution associated with adequate viral suppression.

PRESENTING AUTHOR: M Hennessy

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