Presence of the CYP2B6 516G> T polymorphism, increased plasma Efavirenz concentrations and early neuropsychiatric side effects in South African HIV-infected patients

Data from 80 patients is presented. Genetic polymorphisms in exon 4 of the CYP2B6 gene were identified using PCR amplification of this region followed by sequencing of the amplification products. EFV concentrations were analysed by UPLC-MS/MS. Assessment of the presence of CNS related side effects following EFV initiation were elicited with the use of a questionnaire together with physical examination.Plasma EFV concentrations displayed high inter-individual variability amongst subjects with concentrations ranging from 94 μg/l to 23227 μg/l at 2 weeks post initiation of treatment. For the 516G > T polymorphism the following frequencies were observed 23% of patients were TT homozygous, 36% GG and 41% GT. The TT homozygous patients had significantly higher EFV concentrations vs. those with the wild (GG) genotype (p < 0.05). Patients who experienced no side effects had significantly lower EFV plasma concentrations vs. the group of patients which experienced the most severe side effects (p < 0.05).The significant association between the 516G > T polymorphism and plasma EFV concentrations has been demonstrated in this study. A rapid and sensitive method for the measurement of plasma EFV concentration was developed and validated.Sub-Saharan Africa bears the greatest burden of HIV infection worldwide with data estimating that one in five adults between the ages of 15-49 years is infected [1]. Currently over 400 000 patients receive anti-retroviral (ARV) therapy at South African state hospitals [1]. Efavirenz (EFV), a non- nucleoside reverse transcriptase inhibitor (NNRTI), forms part of the first line therapy for many of these HIV infected individuals. The ARV experience is relatively new to South Africa in comparison to many developed nations and studies looking at adverse effects of treatment and long-term treatment complications are only now beginning to emerge. Clinical trials have reported central nervous system (CNS) side effects in >50% of patients following commenc