Prevalence of Cytochrome P450 2B6 Single Nucleotide Polymorphism in an HIV-Positive Cohort in Jos, Nigeria: Implication for HIV Therapy.

Abstract

Background:Africans exhibit great diversity in cytochrome P450 2B6 isoenzyme (CYP2B6), the major enzyme in efavirenz metabolism.Aim:We examined the frequency of two functional single nucleotide polymorphisms (SNPs) of the CYP2B6 pharmacogene in HIV-infected Nigerians on efavirenz-based antiretroviral therapy. The potential implications of the SNPs for HIV therapy were discussed.Materials and Methods:A cross-sectional study conducted from July 2018 to December 2018 in a tertiary health facility in Nigeria. A random sample of a clinic cohort of HIV-infected adult Nigerians of different ethnicities was characterized for two key SNPs; CYP2B6:516G>, and CYP2B6:983T > C, defining the alleles CYP2B6*6 and CYP2B6*18, respectively. Hardy–Weinberg equilibrium was calculated to evaluate the genotype frequency distribution.Results:Genotyping was successful for 262 (83%) of the 316 study participants. Of those with genotype results, mean age was 41 ± 8 years and 182 (69.5%) were female. The CYP2B6:516 G/G (extensive metabolizers), CYP2B6:516 G/T (intermediate metabolizers), and CYP2B6:516 T/T (poor metabolizers) genotype frequency was 35.9%, 46.6%, and 17.6%, respectively. Also, 88.9% and 11.1% of participants were carriers of the CYP2B6:983 T/T and CYP2B6:983 T/C (poor metabolizers) genotypes, respectively. There were no gender or age-related differences in the genotype distribution. The CYP2B6:516G >T allele frequencies showed no significant deviations from the Hardy-Weinberg equilibrium (P = 0.66).Conclusions:The intermediate metabolizer genotype was more common than the extensive and poor metabolizer genotypes in our study sample. We recommended further studies to investigate the risk of efavirenz underexposure and overexposure in carries of the extensive and poor metabolizer genotypes respectively in our patient population.