Genotypic Frequencies of Cyp2b6, Cyp3a5 and Sult1a1 Polymorphism among HIV Patients on Nevirapine-Based Antiretroviral Therapy at the Korle-Bu Teaching Hospital

Abstract

Background: A major constraint in the management of People Living with Human Immunodeficiency Virus, with highly active antiretroviral therapy is the high incidence of adverse drug reaction among patients. Nevirapine, a non-nucleoside reverse transcriptase inhibitor is among the first-line antiretroviral therapy used in Ghana for the management of Human immunodeficiency virus-1 patients. Despite its usefulness, hypersensitivity reaction is a common complication that accounts for patients defaulting during therapy in Ghana. Nevirapine-induced hypersensitivity has been linked to various mutations in the gene encoding the drug metabolizing enzymes but these genetic associations are inconsistent among different populations. General Aim: To determine the genotypic frequencies of CYP2B6, CYP3A5 and SULT1A1 among patients exposed to nevirapine-based antiretroviral therapy. Method: The study was a case-control study that involved seventy Human Immunodeficiency Virus-1 infected patients accessing antiretroviral therapy at the Korle-Bu Teaching Hospital, Accra, Ghana. Based on Clinicians diagnosis, patients who have been on nevirapine combination antiretroviral therapy and have developed nevirapine hypersensitivity within six months after therapy initiation were identified and categorized as cases, and controls if otherwise. Clinical and demographic data of the participants were recorded and the genomic deoxyribonucleic acid was isolated from the whole blood samples. Samples were genotyped for specific single nucleotide polymorphisms in Cytochrome P450 (CYP2B6 983T>C and CYP3A5 14690G>A) and Sulfotransferase 1A1 (SULT1A1 638G>A) using Polymerase chain reaction-Restriction fragment length polymorphism. Logistic regression was used to find the association between the dependent and independent variables in the study. Outcome: Twelve (12) out of the total 70 participants involved in the study, were identified as having nevirapine-induced hypersensitivity (cases) and all the remaining as a control. The mean age of study participants was recorded as 38 ± 9.47 years. Body mass index, CD4 count, sex and age of participants had no significant association with a nevirapine hypersensitivity reaction. The frequencies of CYP2B6 983T>C were 3% in the control group, and 4% in the case group. Also, CYP3A5 14690G>A frequencies were 50% in both case and control group. SULT1A1 638G>A frequencies were recorded as 21% and 22% in case and control group respectively. Risk of nevirapine hypersensitivity development among study participants was estimated using odds ratio (OR) at a 95% confidence interval (CI). Individuals carrying at least one variant allele of CYP2B6 983T>C has 1.67 times more risk (OR=1.67, 95% Cl=1.58-17.55, p =0.67) for developing nevirapine hypersensitivity whereas individuals carrying at least one variant allele of SULT1A1 638G>A has 1.35 times more risk (OR=1.35, 95% Cl=0.38–4.84, p =0.64) and both were statistically not significant (p > 0.05). CYP3A5 14690G>A allele and genotypic frequency was constant in the study population. Conclusion: There was no significant association of CYP2B6 983T>C, CYP3A5 14690G>A, SULT1A1 638G>A to nevirapine hypersensitivity development. The results may offer a preliminary basis for the more rational use of drugs that are substrates for CYP2B6, CYP3A5 and SULT in the Ghanaian population. This may be helpful to maximize optimal responses at the lowest doses, indirectly implying the reduction of unintended toxicities.