552-T. Influence of a Human Multidrug Resistance Genetic Polymorphism on Treatment Outcome in a Large Community-Based Cohort

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Session 75 Poster Session
Resistance to Antiretroviral Chemotherapeutic Agents
Session Time: 4:30-6:30 pm
Room 4E-F

552-T.

Influence of a Human Multidrug Resistance Genetic Polymorphism on Treatment Outcome in a Large Community-Based Cohort
W. Dong, K. Chan, Z. Brumme, R. Hogg, M. V. O'Shaughnessy, and P. R. Harrigan*
British Columbia Ctr. for Excellence in HIV/AIDS, St. Paul's Hosp., Vancouver, Canada

Background: The expression of p-glycoprotein (PGP), an efflux membrane transporter encoded by the human multidrug resistance (MDR1) gene is significantly affected by a single nucleotide polymorphism (SNP) C3435T in MDR1 exon 26. Individuals homozygous for T/T allele have ~4-fold lower PGP expression compared with CC individual, and racial differences in allele frequencies have been observed which have been postulated to have a potential impact on therapy. This study assessed the influence of the SNP (C3435T) in MDR1 exon 26 on response to antiretroviral therapy.
Method: This retrospective study involved 510 antiretroviral naďve individuals starting HIV treatment between June 1996 and August 1998. Genotype for the MDR1 exon 26 was determined by PCR amplification of human DNA and followed by DNA sequencing. Rates of virological failure (a confirmed rebound of pVL to 400 copies HIV-1 RNA/mL or greater) and time to immunological failure (2 successive CD4+ cell counts below baseline) were assessed by Kaplan-Meier analysis on an intent-to-treat basis.
Results: The frequencies of MDR1 exon 26 genotypes C/C, C/T, T/T in the population studied were 29.6%, 33.6%, 36.9%, respectively. Kaplan-Meier estimates of the time to initial treatment were similar for the 3 genotypes using either virological (p=0.309) or immunological (p=0.414) definitions of treatment failure. Similar proportions of individuals achieved virological success in the 3 genotypes.
Conclusion: The single nucleotide polymorphism in exon 26 of human MDR1, C3435T, does not appear to be a reliable indicator of early response to antiretroviral therapy.

Š2002 9^th Conference on Retroviruses and Opportunistic Infections