Polygenic risk score and risk of drug-induced liver injury after initiating antiretroviral therapy in people living with HIV

Introduction Drug-induced liver injury affects some people living with HIV (PWH) during antiretroviral therapy (ART). We examined associations of polygenic risk scores (PRS) with liver injury during ART.Methods We derived PRS using summary statistics from the Veterans Affairs Million Veteran Program (MVP) and the Penn Medicine BioBank (PMBB). We constructed PRS for individuals of African (AFR) and European (EUR) ancestry in 3,619 treatment-naïve participants from ART-naive studies of the Advancing Clinical Therapeutics Globally (ACTG) network. Liver injury was defined as incident grade 3 or greater alanine aminotransferase (ALT) within 48 weeks. Associations were evaluated by multivariable regression models.Results Clinical variables associated with higher baseline ALT values included hepatitis B or C virus infection, increasing BMI and age, and male sex. In analyses of liver injury among 1,897 EUR participants (28 cases, 1869 controls) and 1722 AFR participants (21 cases, 1701 controls), HBV was associated with liver injury in both EUR and AFR participants, and HCV in EUR participants (p < 0.001 for each). PRSALT was not independently associated with incident liver injury in either EUR or AFR participants.Conclusion No association was observed between baseline PRSALT and subsequent liver injury following initiation of ART.