Successful efavirenz dose reduction in HIV type 1-infected individuals with cytochrome P4502B6*6 and*26

Background. Efavirenz ( EFV) is metabolized primarily by cytochrome P450 2B6 ( CYP2B6), and high plasma concentrations of the drug are associated with a G -> T polymorphism at position 516 ( 516G -> T) of CYP2B6 and frequent central nervous system ( CNS) - related side effects. Here, we tested the feasibility of genotype- based dose reduction of EFV. Methods. CYP2B6 genotypes were determined in 456 human immunodeficiency virus type 1 ( HIV- 1) - infected patients who were receiving EFV treatment or were scheduled to receive EFV- containing treatment. EFV dose was reduced in CYP2B6 516G -> T carriers who had high plasma EFV concentrations while receiving the standard dosage ( 600 mg). EFV- naive homozygous CYP2B6 516G -> T carriers were treated with low- dose EFV. In both groups, the dose was further reduced when plasma EFV concentration remained high. Results. CYP2B6 516G -> T was identified in the * 6 allele ( found in 17.9% of our subjects) and a novel allele, * 26 ( found in 1.3% of our patients). All EFV- treated CYP2B6 * 6/* 6 and * 6/* 26 carriers had extremely high plasma EFV concentrations ( 16000 ng/ mL) while receiving the standard dosage. EFV dose was reduced to 400 mg for 11 patients and to 200 mg for 7 patients with persistently suppressed HIV- 1 loads. EFV- containing treatment was initiated at 400 mg in 4 CYP2B6 * 6/* 6 carriers and one * 6/* 26 carrier. Two of them still had a high plasma EFV concentration while receiving that dose, and the dose was further reduced to 200 mg, with successful HIV- 1 suppression. CNS- related symptoms improved with dose reduction in 10 of the 14 patients, although some had not been aware of the symptoms at initial dosage. Conclusions. Genotype- based EFV dose reduction is feasible in CYP2B6 * 6/* 6 and * 6/* 26 carriers, which can reduce EFV- associated CNS symptoms.