Hepatic Markers and Immunological Trajectories in a Cohort of Patients with HIV and Hepatitis C Virus Coinfection Treated with Direct-Acting Antivirals

Abstract

Persons with HIV (PWH) have disproportionate hepatitis C virus (HCV) infection prevalence and liver-related morbidity and mortality. These sequelae may be alleviated by curative direct-acting antiviral (DAA) treatment; however, longitudinal effects of DAAs on clinical biomarkers are not well-characterized. We included PWH enrolled in the HIV Outpatient Study (HOPS) who were prescribed DAAs and DAA-naïve PWH of comparable age, sex, race/ethnicity, and fibrosis-4 (FIB-4) profiles. We contrasted the DAA effect on longitudinal trajectories of immunological and hepatic markers using generalized linear mixed models (GLMM) from 2010 to 2020. Of 347 PWH/HCV coinfection, median age was 53.8 years, 30.5% were women, 67.1% were publicly insured, 44.4% were non-Hispanic Black, and 153 (44.1%) were prescribed DAAs (median follow-up = 3.55 years). In multivariable GLMM analysis, DAA treatment was associated with [mean (95% confidence interval)] faster decline in alanine aminotransferase of −7.86 mu/µL/year (−15.39, −0.33) and faster increase in platelets of 6.99 mu/µL/year (2.89, 11.09). Changes in aspartate aminotransferase were comparable between groups. FIB-4 decreased in the DAA-treated but not the DAA-naïve group: −0.26 (−0.41, −0.11) versus 0.02 (−0.16, 0.20)/year, respectively. There was a faster increase in cluster of differentiation (CD)4 count of 0.05 (0.03–0.08) and CD8 count of 0.04 (0.02–0.07) log cells/mL/year in the DAA-treated compared with the DAA-naïve group (p < .001), but not in the CD4/CD8 ratio (p = .36). Among U.S. PWH/HCV coinfection treated with DAAs, we found modest changes in immunological markers and substantial improvements in hepatic markers modeled over 4 years of DAA treatment. Curative DAA treatment is critical to mitigate advanced liver fibrosis.