High prevalence of the CYP2B6 516G→T(*6) variant and effect on the population pharmacokinetics of efavirenz in HIV/AIDS outpatients in Zimbabwe

Abstract

The CYP2B6*6 allele occurs at a high frequency in people of African origin and is associated with high efavirenz concentrations. Simulations indicate that an a priori 35% dose reduction in homozygous CYP2B6*6 patients would maintain drug exposure within the therapeutic range in this group of patients. Our preliminary results suggest the conduct of a prospective clinical dose optimization study to evaluate the utility of genotype-driven dose adjustment in this population.

Pharmacogenetics of CYP2B6, CYP2A6 and UGT2B7 in HIV treatment in African populations: focus on efavirenz and nevirapine

“…In a study involving 101 HIV-positive Batswana, the CYP2B6*6 allele was present in 36.6% individuals, and the homozygous haplotype was present in 17.8% of individuals (Gross et al, 2008). A high allele frequency of 49% for the *6 allele was seen in HIV patients in Zimbabwe (Nyakutira et al, 2008). The CYP2B6*6 allele frequency also differed significantly between a Zimbabwean and a Ugandan population, being 48 and 17% (p50.004), respectively (Jamshidi et al, 2010).…”

CYP2B6*6 Screening; Potential Benefits and Challenges in HIV Therapy in Sub-Saharan Africa

“…Although concerns have been raised regarding the possibility of virologic failure with lower efavirenz doses, this would be unlikely if medication adherence and drug monitoring of lower dose regimens is mainted in the patients. A comprehensive genetic analysis of CYP2B6 polymorphisms and their association with EFV concentrations in the largest Chinese HIV-infected patient cohort suggested that personalization of medical care may be feasible if these genomic markers are validated and incorporated in EFV-containing treatments [14].…”

A simple, rapid, economical, and practical method for the determination of efavirenz in plasma of Chinese AIDS patients by reverse phase high-performance liquid chromatography with ultraviolet detector

“…Efavirenz is mainly metabolized by CYP2B6 enzyme. However, cytochrome P450 2B6 gene exhibits highly degrees of polymorphism (2), which has a great difference in allele frequency among races, thus leading to obvious differences in efavirenz plasma concentration, either among individuals or among races (3)(4)(5)(6). In addition, rifampicin and voriconazole, etc., which is often simultaneously used in HIV-infected patients for concurrent diseases, have interactions with efavirenz and affect efavirenz plasma concentration.…”