MDR1 gene polymorphisms and phase 1 viral decay during HIV-1 infection: an adult AIDS Clinical Trials Group study.

Haas DW, Wu H, Li H, Bosch RJ, Lederman MM, Kuritzkes D, Landay A, Connick E, Benson C, Wilkinson GR, Kessler H, Kim RB
J Acquir Immune Defic Syndr. 2003 34 (3): 295-8

PMID: 14600574

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%.

MeSH Terms (20)

Adult Alleles ATP Binding Cassette Transporter, Subfamily B, Member 1 CD4 Lymphocyte Count CD4-Positive T-Lymphocytes Drug Therapy, Combination Female Genes, MDR HIV-1 HIV Infections HIV Protease Inhibitors Humans Lamivudine Male Middle Aged Polymorphism, Single Nucleotide Retrospective Studies Ritonavir RNA, Viral Zidovudine

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