Functional CYP2B6 variants and virologic response to an efavirenz-containing regimen in Port-au-Prince, Haiti.
J Antimicrob Chemother
; 69(8): 2187-90, 2014 Aug.
Article
en En
| MEDLINE
| ID: mdl-24695352
ABSTRACT
OBJECTIVES:
Efavirenz is widely prescribed for HIV-1 infection. Three polymorphisms in CYP2B6 define plasma efavirenz trough concentration strata that vary across an â¼10-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.Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Infecciones por VIH
/
VIH-1
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Benzoxazinas
/
Citocromo P-450 CYP2B6
Tipo de estudio:
Clinical_trials
/
Guideline
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Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Límite:
Adult
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Female
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Humans
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Male
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Middle aged
País/Región como asunto:
Caribe
/
Haiti
Idioma:
En
Revista:
J Antimicrob Chemother
Año:
2014
Tipo del documento:
Article
País de afiliación:
Estados Unidos