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Haas David W. MD; Wu, Hulin PhD; Li, Haihong PhD; Bosch, Ronald J. PhD; Lederman, Michael M. MD; Kuritzkes, Daniel MD; Landay, Alan PhD; Connick, Elizabeth MD; Benson, Constance MD; Wilkinson, Grant R. PhD; Kessler, Harold MD; Kim, Richard B. MD
JAIDS Journal of Acquired Immune Deficiency Syndromes: November 1st, 2003
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Abstract:Human CD4+ T cells express P-glycoprotein (P-gp), the ATP binding cassette efflux transporter encoded by MDR1. A common MDR1 single-nucleotide polymorphism in exon 26 (C3435T), which is linked to an exon 21 polymorphism (G2677T/A) and reportedly alters expression, has been associated with greater CD4+ T-cell increases during antiretroviral therapy. P-gp overexpression prevents apoptosis and inhibits HIV-1 replication in model systems, suggesting a potential effect on T-cell turnover. This study explored relationships between MDR1 polymorphisms and phase 1 viral decay among 31 HIV-infected individuals initiating antiretroviral therapy. Position 3435 genotypes were CC in 7 (23%), CT in 14 (45%), and TT in 10 (32%). Position 2677 genotypes were GG in 8 (26%), GT in 18 (58%), and TT in 5 (16%). There was no significant relationship between allelic variants in either exon 26 or 21 and phase 1 or phase 2 viral decay, changes in lymphocyte subsets over time, or plasma trough ritonavir concentrations. It is concluded with 95% confidence that phase 1 viral decay differences between exon 26 TT and CC groups are unlikely to exceed 18%.

Received for publication June 3, 2003; accepted July 15, 2003.

© 2003 Lippincott Williams & Wilkins, Inc.