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Int J HIV AIDS Res. 2017;4(3):154-160. doi: 10.19070/2379-1586-1700031. Epub 2017 Sep 5.

Pharmacogenetic Associations with ADME Variants and Virologic Response to an Initial HAART Regimen in HIV-Infected Women.

Author information

1
Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor, MI, USA.
2
Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
3
Department of Medicine, Montefiore Medical Center and Albert Einstein College of Medicine, Bronx, NY, USA.
4
Departments of Medicine, Stroger Hospital and Rush University, Chicago, IL, USA.
5
Department of Medicine and Community Health, SUNY Health Sciences Center, Brooklyn, NY, USA.
6
Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
7
Department of Clinical Pharmacy, University of California, School of Pharmacy, San Francisco, CA, USA.
8
Department of Medicine, Georgetown University School of Medicine, USA.

Abstract

Background:

Clinical response to highly active antiretroviral therapy (HAART) varies among different populations. A portion of this variability may be due to variation in genes involved in the absorption, distribution, metabolism, and excretion (ADME) of HAART.

Design:

To identify genetic factors involved in virologic responses to HAART, 13 genes in ADME pathways were analyzed in a cohort of HIV-infected women on HAART. A total of 569 HIV-positive participants from the Women's Interagency HIV Study who initiated HAART from 1994-2012 and had genotype data were included in these analyses.

Methods:

Admixture maximum likelihood burden testing was used to evaluate gene-level associations between common genetic variation and virologic response (achieving <80 viral copies/mL) to HAART overall and with specific drug classes. Results: Six statistically significant (P<0.05) gene-level burden tests were observed with response to specific regimen types. CYP2B6, CYP2C19 and CYP2C9 were significantly associated with response to protease inhibitor (PI)-based regimens. CYP2C9, ADH1A and UGT1A1 were significantly associated with response to triple nucleoside reverse transcriptase inhibitor (NRTI) treatment.

Conclusions:

Although no genome-wide associations with virologic response to HAART overall were detected in this cohort of HIV-infected women, more statistically significant gene-level burden tests were observed than would be expected by chance (two and a half expected, six observed). It is likely that variation in one of the significant genes is associated with virologic response to certain HAART regimens. Further characterization of the genes associated with response to PI-based treatment is warranted.

KEYWORDS:

ADME; HAART; HIV; Pharmacogenomics; Women

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