ABCB1 Polymorphism in HIV-Infected Individuals Taking Antiretroviral Drugs

ABC transporter P-glycoprotein (P-gp) and its expression enhance elimination and reduce drug exposure. The elimination of non-nucleoside reverse-transcriptase inhibitor (NNRTIs) drugs is associated with ABCB1 gene. Drug exposure is impacted by variants in the ABCB1 gene. Hence, the aim of the study was to investigate the association of ABCB1 1236 C/T and 3435 C/T polymorphisms with the modulation of antiretroviral (ARV)-associated hepatotoxicity. This is a cross-sectional study. Genotyping of the ABCB1 1236C/T and 3435C/T polymorphisms was performed in 165 HIV-infected individuals (34 with hepatotoxicity and 131 without hepatotoxicity) and 155 healthy controls using the PCR-RFLP method. The TC haplotype was likely to be associated with a higher risk of severe hepatotoxicity (OR = 1.96, p = 0.06), while CC and TT haplotypes were associated with a reduced risk of severe hepatotoxicity (OR = 0.34, p = 0.039; OR = 0.16, p = 0.006; OR = 0.09, p = 0.003). The ABCB1 3435CT genotype along with alcohol usage revealed a risk of HIV disease progression (OR = 2.47, p = 0.12). The ABCB1 1236TT genotype along with nevirapine (NVP) usage exhibited a risk for hepatotoxicity severity (OR = 2.11, p = 0.55). The ABCB1 3435CT genotype along with alcohol + NVP usage bared a risk of acquisition of hepatotoxicity (OR = 2.04, p = 0.23). In conclusion, ABCB1 haplotypes may influence the severity of ARV-induced hepatotoxicity. While individual polymorphisms and their interaction with alcohol or drug regimen showed no significant association, the 1236TT genotype with NVP use and the TC haplotype suggested a potential risk. Protective effects were observed for CC and TT haplotypes. Larger studies are warranted to confirm these findings and assess clinical relevance.