Analysis of MDR1 Polymorphisms Among HIV-Infected Individuals on ARV Therapy from Western India

Abstract

Background: MDR1 is involved in the transport of numerous drugs. Polymorphism of MDR1 is linked with the treatment outcome. ARV regimen is being used to manage the progression of HIV infection. Ethnic disparities have been observed in the distribution of MDR1 genotypes. Methods: MDR1 polymorphism (1236 C/T, 3435 C/T) was genotyped in 34 individuals with ARV-associated hepatotoxicity, 131 HIV-infected, and one-fifty-five healthy by utilization of PCR-RFLP. Results: Haplotype TC exposed the greater risk for hepatotoxicity severity when compared between individuals with hepatotoxicity and HIV infected (OR=1.96, P=0.06). While haplotypes TT and CC bared a reduce risk for hepatotoxicity severity (OR= 0.16, P=0.006; OR= 0.46, P=0.06). Haplotype TT and CC displayed a decrease risk of hepatotoxicity severity while compared between individuals with hepatotoxicity and healthy (OR=0.09, P=0.003; OR=0.34, P=0.03). A higher occurrence of MDR1 1236TT genotype was seen among patients with hepatotoxicity who consumed alcohol (28.6% versus 14.8%, OR=1.50). In patients with hepatotoxicity taking nevirapine, there was an increased incidence of MDR1 1236TT genotype in contrast with efavirenz (21.7% versus 9.1%, OR=2.11). In HIV-infected people taking nevirapine, MDR1 1236CT, 1236TT genotypes found to be increased compared with efavirenz (43.7% versus 33.3%, OR=1.66; 12.6% versus 8.3%, OR=1.96). A higher occurrence of MDR1 1236TT genotype has happened in hepatotoxicity cases having both alcohol and nevirapine (40.0% versus 16.67%, OR=2.21). Conclusion: MDR1 haplotypes may have an influence on the severity of hepatotoxicity. Individual utilizing nevirapine and alcohol with MDR1 1236TT and 3435CT genotypes may have combined effect on vulnerability of severity of hepatotoxicity and progression of HIV infection