biostudies-literatureSimoncini GIntramural CDC HHS400-410https://www.ebi.ac.uk/biostudies/studies/S-EPMC12371430biostudies-literatureUnknown41(8)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 (<i>p</i> < .001), but not in the CD4/CD8 ratio (<i>p</i> = .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.AIDS research and human retrovirusesHepatic Markers and Immunological Trajectories in a Cohort of Patients with HIV and Hepatitis C Virus Coinfection Treated with Direct-Acting Antivirals.PMC12371430CC999999Li JHIV Outpatient Study InvestigatorsMayer CCollins LFSimoncini GBattalora LBuchacz KfalseHepatic Markers and Immunological Trajectories in a Cohort of Patients with HIV and Hepatitis C Virus Coinfection Treated with Direct-Acting Antivirals.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 (<i>p</i> < .001), but not in the CD4/CD8 ratio (<i>p</i> = .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.2025-01-01T00:00:00Z2025 Aug2026-05-08T10:51:12.413Z2026-05-03T03:06:00.609ZS-EPMC123714304039761810.1089/aid.2025.0001