CYP1A1 genotype modifies the impact of smoking on effectiveness of HAART among women

David N. Feldman, Joseph G. Feldman, Ruth Greenblatt, Kathryn Anastos, Leigh Pearce, Mardge Cohen, Stephen Gange, Suzanne Leanza, Robbie Burk

Research output: Contribution to journalArticlepeer-review

30 Scopus citations

Abstract

We have recently shown that cigarette smoking is associated with lesser responses to potent antiretroviral therapies. Certain Cytochrome P-450 enzymes activate compounds derived from tobacco smoke into toxic forms that may promote HIV-1 gene expression through promotion of DNAadduct formation by the oxidation of chemical constituents of cigarette smoke, such as polyaromatic hydrocarbons and dioxins. To explore the association between environmental and genetic factors to viral replication in women who smoke and receive highly active anti-retroviral therapy (HAART), we assessed the impact of polymorphisms in a panel of four Cytochrome P-450 genes (CYP1A1, CYP2A6, CYP2D6, and CYP2E1) and two Glutathione S-transferase genes (GSTM1 and GSST1) in 924 participants of the Women's Interagency HIV Study (WIHS). Our findings showed that GSTM1 and GSST1 deletions were not associated with HAART effectiveness. By contrast, homozygosity for the CYP1A1-m1 polymorphism, was associated with impaired viral response to treatment among smokers (relative hazard (RH) = 0.54; 95% confidence interval = 0.31-0.94) after adjustment for pretreament viral load, CD4 count, age, hepatitis C infection, prior HAART therapy and race, although it had no effect among nonsmokers. We conclude that the association of the CPY1A1-m1 variant with a reduced response to HAART therapy in HIV infected smokers is consistent with this enzyme's role in the metabolic conversion of environmental toxins to DNA adducts, which may directly promote HIV-1 gene expression.

Original languageEnglish (US)
Pages (from-to)81-93
Number of pages13
JournalAIDS Education and Prevention
Volume21
Issue numberSUPPL. 3
DOIs
StatePublished - Jun 2009

ASJC Scopus subject areas

  • Health(social science)
  • Public Health, Environmental and Occupational Health
  • Infectious Diseases

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