Adverse Impact of HIV-1 on Long-term Outcomes Following HCV DAA Treatment: Final Results of ACTG A5320, the Viral Hepatitis C Infection Long-term Cohort Study (VHICS)

Abstract

Background Long-term outcome data after HCV treatment are limited, particularly for comparisons between persons with and without HIV. Methods A5320, a prospective cohort study that enrolled participants within 12 months of completing HCV DAA therapy, with or without sustained virologic response (SVR). The primary endpoint was composite: time to death or development of a targeted diagnosis. Component outcomes (death and targeted diagnosis) and liver-related events were also analyzed. The effects of HIV serostatus and HIV RNA and CD4, and liver disease stage on the outcomes were assessed. Follow-up was designated for 5 years. Results 332 participants enrolled: 184 with HIV/HCV (130 SVR) and 148 with HCV (125 SVR). The primary analysis was dominated by targeted diagnoses. Increased rates of targeted diagnoses were seen in HCV-HIV/SVR compared to HCV/SVR (p=0.016) with an incidence rate of 6.7 and 3.4 per 100 person-years, respectively. Among persons without HIV, higher rates of targeted diagnoses were observed in NonSVRs (p=0.007), 10.8 vs 3.4/100 person-years. No significant difference was seen by SVR status among those with HIV. There were 15 deaths; all liver-related deaths (n=4) occurred in NonSVR groups. Conclusions HCV cure following therapy reduces subsequent development of new clinical events, supporting the use of SVR as a predictor for clinical outcomes. Despite HIV control, a significant decrease in incident events or mortality was not demonstrated for PWH who achieved SVR, suggesting co-infection attenuates the beneficial impact of SVR. Research is needed to better define mechanisms accounting for the long-term negative impact of controlled HIV infection.