Genetic Variants of Drug Metabolizing Enzymes and Drug Transporter (ABCB1) as Possible Biomarkers for Adverse Drug Reactions in an HIV/AIDS Cohort in Zimbabwe
Milcah Dhoro, Bernard Ngara, Gerald Kadzirange, Charles Nhachi and Collen Masimirembwa
Affiliation: Department of Molecular Sciences, African Institute of Biomedical Science & Technology, Dominion House, 211 Herbert Chitepo and Sam Nujoma Street, Harare, Zimbabwe.
A study was conducted in an HIV/AIDS Zimbabwean cohort to assess possible associations of
pharmacogenetic variants with common adverse drug reactions (ADRs) during anti-retroviral treatment (ART) and/or
tuberculosis (TB) treatment. Genotype and allele frequencies for CYP2B6 G516T, CYP2B6 T983C, CYP2A6*17, ABCB1
rs10276036 C>T, NAT2*5 and NAT2*14 were similar to those reported in literature for other African populations. The
CYP2B6 516TT genotype and male gender were significantly associated with occurrence of Efavirenz induced central
nervous system disorders (OR 20.58, p=0.004) and the ABCB1 rs10276036TT genotype with Nevirapine induced skin
hypersensitivity (OR 4.01, p=0.04). For Stavudine, time on treatment was the main factor in development of
lipodystrophy (OR 1.06, p<0.0001). For isoniazid, increasing patient age was associated with peripheral neuropathy (OR
1.05, p=0.001). Although genetic polymorphisms may play a role in predicting occurrence of ADRs, this study also
indicates that other factors (gender, age, treatment time) are crucial in predicting drug-induced adverse effects.
Keywords: Antiretroviral treatment, adverse drug reactions, genetic polymorphisms, HIV/AIDS.
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