Functional CYP2B6 variants and virologic response to an efavirenz-containing regimen in Port-au-Prince, Haiti.

Haas DW, Severe P, Jean Juste MA, Pape JW, Fitzgerald DW
J Antimicrob Chemother. 2014 69 (8): 2187-90

PMID: 24695352 · PMCID: PMC4100704 · DOI:10.1093/jac/dku088

OBJECTIVES - Efavirenz is widely prescribed for HIV-1 infection. Three polymorphisms in CYP2B6 define plasma efavirenz trough concentration strata that vary across an ∼10-fold range. We characterized associations between human genetic polymorphisms and virologic response among participants who received efavirenz-containing regimens in a prospective clinical trial.

METHODS - We genotyped 76 polymorphisms in CYP2B6 (including those that define efavirenz concentration strata), CYP2A6, CYP3A4, CYP3A5 and ABCB1 and week 48 virologic responses in 360 Haitians who initiated efavirenz-containing regimens in protocol HT 001. Associations were characterized by logistic regression analysis and Fisher's exact test.

RESULTS - Proportions with HIV-1 RNA <50 or <200 copies/mL did not differ across 10 CYP2B6 metabolizer strata. In analyses that combined strata into three metabolizer levels (extensive, intermediate and slow), the respective proportions were 0.79, 0.79 and 0.81 (<50 copies/mL cut-off) and 0.84, 0.86 and 0.87 (<200 copies/mL cut-off). Genetic associations were not identified after controlling for baseline variables or with other polymorphisms after adjusting for multiple comparisons.

CONCLUSIONS - Virologic failures in HT 001 were not explained by genetic polymorphisms known to define the lowest plasma efavirenz concentration stratum.

© The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

MeSH Terms (22)

Adult Anti-HIV Agents ATP Binding Cassette Transporter, Subfamily B Benzoxazines Cytochrome P-450 CYP2A6 Cytochrome P-450 CYP2B6 Cytochrome P-450 CYP2B6 Inducers Cytochrome P-450 CYP3A Female Genetic Association Studies Haiti HIV-1 HIV Infections Humans Male Middle Aged Polymorphism, Single Nucleotide Prospective Studies Reverse Transcriptase Inhibitors RNA, Viral Secondary Metabolism Treatment Outcome

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