CYP2B6 Variants and Plasma Efavirenz Concentrations during Antiretroviral Therapy in Port-au-Prince, Haiti

BackgroundPolymorphisms in CYP2B6 are known to predict increased steady-state plasma concentrations of efavirenz. We characterized relationships between genetic polymorphisms and plasma efavirenz concentrations among 45 Haitians who initiated antiretroviral therapy in Port-au-Prince MethodsAn observational study characterized relationships between clinical factors, pharmacokinetics, and treatment response among antiretroviral-naive patients initiating once-daily treatment with efavirenz plus twice-daily treatment with zidovudine and lamivudine. Plasma drug concentrations were determined at weeks 2 and 4. Drug doses were directly observed by field workers or designated family members. We retrospectively characterized relationships between efavirenz concentrations and 50 single-nucleotide polymorphisms in CYP2B6 and several polymorphisms in CYP2A6, CYP3A4, CYP3A5 and ABCB1 ResultsPlasma specimens for efavirenz analysis were obtained from study participants a mean (± standard deviation) of 13.9±1.6 h after they received the dose. As expected, CYP2B6 516G→T was associated with increased plasma efavirenz concentrations (Spearman ρ=0.71; P