NAT2 GENE POLYMORPHISMS IS A RISK FACTOR IN PATIENTSCO-INFECTED WITH HIV AND TUBERCULOSIS

Abstract

Actuality. The number of human immunodeficiency virus (HIV)-infected patients with active tuberculosis (TB) and multiple/extensive drug resistance has increased in recent years. Backup drugs with high hepatotoxicity are used in the treatment regimens of this category of patients. Identification of markers of adverse events in the form of hepatotoxicity by determining the type of acetylation in patients with HIV infection and TB when prescribing drugs metabolized by NAT2 enzyme may influence the selection of optimal doses and reduce the toxic effect on the liver. The aim of the research was to determine the features of N-acetyl-transferase 2 (NAT2) gene polymorphisms in HIVinfected patients with active tuberculosis with advanced drug-induced liver damage. Materials and мethods. NAT2 genotype and haplotype determination was performed in 151 TB/HIV-infected patients receiving drugs with different types of acetylation. Determination of allele frequencies for six single nucleotide polymorphisms (SNPs) of the genotype was used by real-time PCR, allele verification was confirmed by pyrosequencing using the AmpliSense® Pyroskrin PHARMA-screen-2a reagent kit. Analysis was performed using IBM SPSS Statistics 29.0.2.0. significance of differences in frequency distribution of variables was used for Pearson's Chi-square criterion. It was used as a measure of relative risk with a regression confidence interval of 95% and a significance level of 5% (p <0.05). Reliability of differences in median values was determined based on the Mann-Whitney criterion for two groups, the Kraskell-Wallis criterion for multiple comparison of groups (p <0.05). Results. A larger proportion of patients were found to have a slow type of acetylation (57.6%). Among the haplotypes causing the slow type of acetylation the most frequent were haplotypes NAT2*5B (48.3%) and NAT2*6A (40.2%). The observation showed more frequent increase of aminotransaminase activity from 3 to 10 norms from the upper limit in patients with slow type of acetylation of the NAT2 enzyme gene. They accounted for 43.7% of the total number of identified cases of the slow type of acetylation. The median value of aminotransaminase levels was significantly higher in patients with slow type of acetylation compared to patients in the fast acetylation group (p < 0.0001). Conclusions. Slow type of acetylation should be considered a high risk factor for hepatotoxicity in TB/HIV patients when prescribed anti-TB drugs. Data on isoniazid acetylation and NAT2 genotypes can be used to improve treatment quality and reduce the risk of isoniazid toxicity in TB treatment.