Open AccessCYP2B6 G516T and ABCB‐1 C3435T polymorphisms: implications for efavirenz‐associated liver toxicity in HIV/tuberculosis co‐infected Thai adults
Author(s) -
Uttayamakul S,
Manosuthi W,
Likasakul S,
Shioda T,
Khusmith S
Publication year - 2012
Publication title -
journal of the international aids society
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.724
H-Index - 62
ISSN - 1758-2652
DOI - 10.7448/ias.15.6.18409
Subject(s) - efavirenz , cyp2b6 , medicine , lamivudine , pharmacology , rifampicin , genotype , tuberculosis , virology , gastroenterology , cyp3a4 , human immunodeficiency virus (hiv) , biology , viral load , antiretroviral therapy , cytochrome p450 , chronic hepatitis , virus , pathology , genetics , metabolism , gene
Cytochrome P450 2B6 ( CYP2B6 ) and ATP‐binding cassette, sub‐family B ( ABCB‐1 ) play an important role in metabolism and transport of anti‐retroviral therapy (ART) agents. CYP2B6 516TT and ABCB‐1 3435CT polymorphisms affected plasma efavirenz levels. Efavirenz‐based ART was proofed to be beneficial in HIV/tuberculosis co‐infection management; however, the drug‐drug interactions and toxicity are major concerns. Factors affecting adverse drug events and liver toxicity were investigated in this study. Seventy‐one HIV patients with tuberculosis receiving efavirenz (600 mg/day)‐based ART were enrolled in the randomized trial: the N2R study in Bamrasnaradura Infectious Diseases Institute, Thailand. After 12 weeks of ART, 65 rifampicin recipients continued in the analysis of the factors influenced drug toxicity. Plasma efavirenz, serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), total and direct bilirubins were determined. CYP2B6 and ABCB‐1 polymorphisms were genotyped. Mann‐Whitney U test was used to compare genotypes and laboratory parameters. CYP2B6 516TT and ABCB‐1 3435CT genotypes were found in 9 (13.85%) and 33 (50.77%) patients, respectively, while six (9.23%) carry both ‐516TT and ‐3435CT genotypes. Patients with 516TT genotype had significantly higher mean rank plasma efavirenz than GT and GG genotypes (54.78 vs. 29.50, p=1.97x10 −4 ) while those carrying 3435CT had slightly higher than CC and TT genotypes. Patients carrying both ‐516TT and ‐3435CT had higher mean rank efavirenz levels than those without these two genotypes (60.17 vs. 30.24, p=2.21x10 −4 ), and had significantly different ALT, total and direct bilirubin levels (p=0.044, 0.009, 0.021, respectively). CYP2B6 516TT and ABCB‐1 3435CT influenced plasma efavirenz levels and related to higher levels of ALT, total and direct bilirubin in patients implication for drug toxicity. The results might be useful for personalized therapy due to their impact on ART adherence related to drug resistance and treatment failure.