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Comprehensive information on the effects of cytochrome P450 2B6 (CYP2B6) polymorphisms, clinical factors, and drug-drug interactions on efavirenz concentrations in HIV/tuberculosis-coinfected (HIV/TB) patients is unavailable. A total of 139 HIV/TB adults, 101 of whom received a rifampin-containing anti-TB regimen, were prospectively enrolled to receive efavirenz (600 mg)/tenofovir/lamivudine. Nine single nucleotide polymorphisms (SNPs) within CYP2B6 were genotyped. Plasma efavirenz concentrations were measured at 12 weeks. The median (interquartile range [IQR]) efavirenz concentration was 2.3 (1.4 to 3.9) mg/liter. The SNPs (frequencies of heterozygous and homozygous mutants) were 64C&gt;T (10% and 1%), 499C&gt;G (0% and 0%), 516G&gt;T (47% and 8%), 785A&gt;G (54% and 10%), 1375A&gt;G (0% and 0%), 1459C&gt;T (3% and 0%), 3003C&gt;T (44% and 27%), 18492T&gt;C (39% and 6%), and 21563C&gt;T (57% and 5%). The four most frequent CYP2B6 haplotypes identified were *1/*6 (41%), *1/*1 (35%), *1/*2 (7%), and *6/*6 (7%). The heterozygous/homozygous mutation associated with low efavirenz concentrations was 18492T&gt;C (P &lt; 0.001), and those associated with high efavirenz concentrations were 516G&gt;T, 785A&gt;G, and 21563C&gt;T (all P &lt; 0.05). Haplotype *1/*1 was associated with low efavirenz concentrations, and *6/*6, *1/*6, and *5/6 were associated with high efavirenz concentrations. As shown by multivariate analysis, low efavirenz concentrations were significantly associated with the *1/*1 haplotype (beta = -1.084, P = 0.027) and high body weight (beta = -0.076, P = 0.002). In conclusion, pharmacogenetic markers of CYP2B6 have the greatest impact with respect to inducing low plasma efavirenz concentrations in HIV/TB Thai patients.

antimicrobial agents and chemotherapy

Impact of Pharmacogenetic Markers of<i>CYP2B6</i>, Clinical Factors, and Drug-Drug Interaction on Efavirenz Concentrations in HIV/Tuberculosis-Coinfected Patients

Impact of Pharmacogenetic Markers ofCYP2B6, Clinical Factors, and Drug-Drug Interaction on Efavirenz Concentrations in HIV/Tuberculosis-Coinfected Patients