PO 8261 CYTOCHROME P450 (CYP2B6*6C.516G>T) VARIANTS IN CONGOLESE INDIVIDUALS WITH HIV AND TB MONO AND DUAL INFECTIONS

Abstract

BackgroundThe inter-individual genetic polymorphism of cytochrome P450 enzymes (CYP), involved in the metabolism of many drugs, partly modulates drug response and toxicity. Single nucleotide polymorphisms of CYP2B6 for example, G516T have been implicated in high- and sub-therapeutic plasma concentration of the current antimalarial, HIV and TB first-line drugs in various geographical regions and thus undermines effective disease management. At present, there is no data on the frequency of CYP2B6 c.516G>T among the Congolese population, despite a significant number of people undergoing antimalarial, HIV and TB treatment that relies on CYP2B6-based drug clearance or activation.MethodsA total of 418 patients with HIV-1 mono-infection, HIV-1 +TB coinfection and P. falciparum infection were genotyped for CYP2B6 c.516G>T polymorphism using PCR-RFLP. The frequencies of the alleles as well as the genotypes (GG, GT and TT) were determined.ResultsThe frequency of CYP2B6 c.516G>T polymorphism was 69% and frequency of G and T alleles were 45% and 55%, respectively. 17.0% (49/288) of participants were GG (extensive metaboliser), 55.2% (159/288) of participants were GT (intermediate metaboliser) and 27.8% (80/288) of participants were TT (poor metabolisers).ConclusionThis study highlights CYP2B6 c.G516T polymorphism as a potential determinant of drug response and toxicity among the Congolese population, particularly those undergoing antiretroviral, malaria and tuberculosis treatment within the current first-line drug policy framework.