Effects of Efavirenz for the Treatment of HIV Section on the Basis of Genetic Polymorphisms

Abstract

Introduction: CYP2B6 is a liver enzyme that is involved in the metabolism of several drugs including Efavirenz, which is one of the mainstay treatments for Acquired Immunodeficiency Syndrome (AIDS) caused by the Human Immunodeficiency Virus (HIV). Polymorphisms in the CYP2B6 gene determine the rate of enzyme activity. One such polymorphism, rs3745274, where there is a change from G to T at codon 516 results in an amino acid change from glutamine to histidine at position 172. The Food and Drug Administration (FDA) USA has recommended this molecular marker as a companion diagnostic test for Efavirenz. Aim: To evaluate the effect of Efavirenz in the treatment of HIV on the basis of genetic polymorphisms. To determine the CYP2B6 genotype of healthy individuals and those with HIV before starting the antiretroviral therapy. To review the reported cases of genetic polymorphisms and document drug toxicity in the selected population. Materials and Methods: A prospective clinical observational study was done at Kamineni Hospital, Hyderabad, Telangana, India, from September 2017 to August 2020 with an inclusion criterion of participants above the age of 18 years who are HIV positive diagnosed by Enzyme Linked Immunosorbent Assay (ELISA) test, reporting to the Outpatient Department (OPD) or getting admitted for treatment with Efavirenz with a sample size of 369 based on the prevalence of CYP2B6 polymorphism in Southern India. Results: Out of the study population, 276 HIV patients and 93 controls were genotyped by Polymerase Chain Reaction (PCR) and subjected to Restriction Fragment Length Polymorphism (RFLP) technique to establish CYP2B6 - 516 G>T polymorphism. About 69% is of GT genotype, 18% is of TT genotype and 13% is of GG genotype. Patients with GT genotype are intermediate metabolisers of the drug, those with TT genotype are poor metabolisers of the drug, and GG genotype is an extensive metaboliser of the drug. Individuals with the 516T allele have low enzyme activity and are poor metabolisers of the drug, causing delayed clearance leading to Adverse Drug Reactions (ADR) causing neurological deficits and cardiac complications. Conclusion: This observation helps the clinician adjust the dose of Efavirenz by studying the genetic polymorphism of the patient. Based on this study, we recommend that all HIV diagnosed patients undergo CYP2B6 genotyping before starting an Efavirenz based regimen to decrease the adverse drug reactions and promote effective Highly Active Antiretroviral Therapy (HAART) therapy.