Clinical and genetic determinants of nevirapine plasma trough concentration

BACKGROUND: Only few data are available on the influence of CYP2B6 and CYP3A4/A5 polymorphisms on nevirapine plasma concentrations in the Caucasian population. Our aim was to assess the impact of CYP2B6 and CYP3A4/A5 polymorphisms on nevirapine plasma concentrations consecutively collected. METHODS: We retrospectively analyzed clinical data of all HIV-positive patients who were followed at the Infectious Diseases Unit, DIBIC Luigi Sacco, University of Milan between January 2000 and December 2015. All patients with at least one nevirapine plasma trough concentration (NVP C(min)) determination were tested for CYP2B6 c.516 G>T, CYP3A4*22C>T and CYP3A5*3 A>G polymorphisms. Univariate and multivariate regression analyses were carried out considering NVP C(min) as the dependent variable and genetic polymorphisms and clinical characteristics as independent variables. RESULTS: A total of 143 patients were evaluated. Most of them were males (61.5%) and Caucasian (92.3%). Overall, NVP C(min) varied from 1571 to 14,189 ng/mL (median = 5063 ng/mL, interquartile range = 3915–6854). The median NVP C(min) significantly differed in patients with different CYP2B6 genotypes, but did not vary in those with different CYP3A phenotypes. In the final general linear model, factors significantly associated with a higher NVP C(min) were each extra unit of T alleles of CYP2B6 rs3745274 (β = 0.328, 95% confidence interval = 0.172–0.484; p < 0.0001), older age (β = 0.362, 95% confidence interval = 0.193–0.532; p < 0.0001) and hepatitis C virus coinfection (β = 0.161, 95% confidence interval = 0.006–0.315; p < 0.041). CONCLUSION: Our study, conducted in a prevalent Caucasian population, highlighted the importance of CYP2B6 genetic variants in influencing nevirapine plasma trough concentration. Furthermore, older age and hepatitis C virus coinfection significantly increase exposure to nevirapine.