MDR1 gene polymorphisms and phase 1 viral decay during HIV-1 infection: an adult AIDS Clinical Trials Group study.
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%.
Haas
David W
DW
Division of Infectious Diseases, Vanderbilt University School of Medicine, 345 24th Avenue, North, Suite 105, Nashville, TN 37212, USA. david.w.haas@vanderbilt.edu
Wu
Hulin
H
Li
Haihong
H
Bosch
Ronald J
RJ
Lederman
Michael M
MM
Kuritzkes
Daniel
D
Landay
Alan
A
Connick
Elizabeth
E
Benson
Constance
C
Wilkinson
Grant R
GR
Kessler
Harold
H
Kim
Richard B
RB
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis / Q000235:genetics; D000328:Adult; D000483:Alleles; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism / Q000502:physiology; D004359:Drug Therapy, Combination; D005260:Female; D019450:Genes, MDR / Q000235:genetics* / Q000502:physiology; D015658:HIV Infections / Q000188:drug therapy* / Q000235:genetics / Q000821:virology; D017320:HIV Protease Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D015497:HIV-1 / Q000235:genetics / Q000502:physiology*; D006801:Humans; D019259:Lamivudine / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics / Q000502:physiology; D012367:RNA, Viral / Q000097:blood; D012189:Retrospective Studies; D019438:Ritonavir / Q000097:blood / Q000494:pharmacology* / Q000627:therapeutic use; D015215:Zidovudine / Q000494:pharmacology / Q000627:therapeutic use
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D017320:HIV Protease Inhibitors; D012367:RNA, Viral; D019259:Lamivudine; D015215:Zidovudine; D019438:Ritonavir