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Journal of personalized medicine
Jun 30, 2022;12 (7):

and Genotype Predicts Glucose Metabolism Disorder among HIV Patients on Long-Term Efavirenz-Based ART: A Case-Control Study.

Wondmagegn Tamiru Tadesse, Eulambius Mathias Mlugu, Workineh Shibeshi, Wondwossen Amogne Degu, Ephrem Engidawork, Eleni Aklillu
Author Information
  1. Wondmagegn Tamiru Tadesse: Department of Pharmacology and Clinical Pharmacology, School of Pharmacy, College of Health Sciences, Addis Ababa University, Addis Ababa P.O. Box 9086, Ethiopia. ORCID
  2. Eulambius Mathias Mlugu: Division of Clinical Pharmacology, Department of Laboratory Medicine, Karolinska Institute, Karolinska University Hospital-Huddinge, 14186 Stockholm, Sweden.
  3. Workineh Shibeshi: Department of Pharmacology and Clinical Pharmacology, School of Pharmacy, College of Health Sciences, Addis Ababa University, Addis Ababa P.O. Box 9086, Ethiopia. ORCID
  4. Wondwossen Amogne Degu: Department of Internal Medicine, School of Medicine, College of Health Sciences, Addis Ababa University, Addis Ababa P.O. Box 9086, Ethiopia. ORCID
  5. Ephrem Engidawork: Department of Pharmacology and Clinical Pharmacology, School of Pharmacy, College of Health Sciences, Addis Ababa University, Addis Ababa P.O. Box 9086, Ethiopia. ORCID
  6. Eleni Aklillu: Division of Clinical Pharmacology, Department of Laboratory Medicine, Karolinska Institute, Karolinska University Hospital-Huddinge, 14186 Stockholm, Sweden. ORCID
PMID: 35887584 DOI: 10.3390/jpm12071087

Abstract

Long-term antiretroviral treatment (cART) increases the risk of glucose metabolism disorders (GMDs). Genetic variation in drug-metabolizing enzymes and transporters may influence susceptibility to cART-associated GMDs. We conducted a case-control study to investigate the association of pharmacogenetic variations with cART-induced GMDs. A total of 240 HIV patients on long-term efavirenz-based cART (75 GMD cases and 165 controls without GMDs) were genotyped for CYP3A4*1B, CYP3A5 (*3,*6), CYP2B6*6, UGT2B7*2, ABCB1 (c.3435C>T, c.4036A>G), and SLCO1B1 (*1b, *5). GMD cases were defined as the presence of impaired fasting glucose, insulin resistance, or diabetes mellitus (DM). Case-control genotype/haplotype association and logistic regression analysis were performed by adjusting for age, sex, and BMI. The major CYP3A haplotype were CYP3A5*3 (53.8%), CYP3A4*1B (17.3%), combinations of CYP3A4*1B, and CYP3A5*6 (10.9%), and CYP3A wild type (7%). CYP3A5*6 allele (p = 0.005) and CYP3A5*6 genotype (p = 0.01) were significantly associated with GMD cases. Multivariate analysis indicated CYP3A haplotype as a significant predictor of GMD (p = 0.02) and IFG (p = 0.004). CYP2B6*6 significantly predicted DM (p = 0.03). CYP3A haplotype and CYP2B6*6 genotype are independent significant predictors of GMD and DM, respectively, among HIV patients on long-term EFV-based cART.

Keywords

CYP2B6 CYP3A5 Ethiopia HIV antiretroviral therapy efavirenz genotype glucose metabolic disorder pharmacogenetic variation

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Grants

  1. 2015-03295/Swedish Research Council
  2. CSA2016S-1618/European and Developing Countries Clinical Trials Partnership
  3. GPO/275/12/20/Swedish International Development Cooperation Agency
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