High plasma efavirenz level and CYP2B6*6 are associated with efavirenz-based HAART-induced liver injury in the treatment of naïve HIV patients from Ethiopia

• Verfasst von: Yimer, Getnet [VerfasserIn]
• Verfasst von: Haefeli, Walter E. [VerfasserIn]
• Verfasst von: Burhenne, Jürgen [VerfasserIn]
• Titel: High plasma efavirenz level and CYP2B6*6 are associated with efavirenz-based HAART-induced liver injury in the treatment of naïve HIV patients from Ethiopia
• Titelzusatz: a prospective cohort study
• Verf.angabe: G. Yimer, W. Amogne, A. Habtewold, E. Makonnen, N. Ueda, A. Suda, A. Worku, W.E. Haefeli, J. Burhenne, G. Aderaye, L. Lindquist and E. Aklillu
• Jahr des Originals: 2011
• Umfang: 8 S.
• Fussnoten: Published online 23 August 2011 ; Gesehen am 05.07.2018
• Titel Quelle: Enthalten in: The pharmacogenomics journal
• Jahr Quelle: 2012
• Band/Heft Quelle: 12(2012), 6, S. 499-506
• ISSN Quelle: 1473-1150
• DOI: doi:10.1038/tpj.2011.34
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1577325923

Abstract

The objective of this study was to assess the incidence, timing and identify pharmacogenetic, efavirenz (EFV) pharmacokinetic and biochemical predictors of EFV-based antiretroviral therapy (ART) drug-induced liver injury (DILI). ART-naïve HIV patients (n=285) were prospectively enrolled. Pretreatment laboratory evaluations included hepatitis B surface antigen and C antibody, CD4 count and viral load. Liver tests were done at baseline, 1st, 2nd, 4th, 8th, 12th, 24th and 48th weeks during ART. Plasma EFV and 8-hydroxyefvairenz concentration was determined at week 4 using liquid chromatography-mass spectrometry. CYP2B6, CYP3A5, ABCB1 3435C/T and UGT2B7*2 genotyping was done using Taqman genotyping assay. Data were analyzed using survival analysis and Cox proportional hazards model. The incidence of DILI was 15.7% or 27.9 per 100 person-years and that of severe injury was 3.4% or 6.13 per 100 person-years. The median time for the development of DILI and severe injury was 2 and 4weeks after initiation of ART, respectively. There was significant association of DILI with lower baseline platelet, albumin, log plasma viral load and CD4 count (P=0.031, 0.037, 0.06 and 0.019, respectively). Elevated baseline alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, plasma EFV level and CYP2B6*6 were good predictors for the development of DILI (P=0.03, 0.01, 0.016, 0.017 and 0.04, respectively). We report for the first time CYP2B6*6 as a putative genetic marker and high plasma EFV concentration as intermediate biomarker for vulnerability to EFV-induced liver injury in HIV patients. CYP2B6 genotyping and/or regular monitoring of EFV and lever enzymes level during early therapy is advised for early diagnosis and management of DILI.