Despite HCV cure, individuals with HIV and prior HCV infection remained at higher risk for mortality than those with HIV alone, especially 12 months after cure.
“Direct-acting antivirals (DAAs) cure more than 90% of people with hepatitis C virus (HCV) infection,” Maria-Bernarda Requena, PhD-candidate, notes. “Previous studies exploring mortality in HIV/HCV coinfection versus HCV monoinfection had pointed to the persistence of a high mortality rate despite HCV cure in people with HIV, partly due to a higher liver-related mortality in the years following sustained virologic response in people with pre-existing liver disease.”
For a study published in AIDS, Requena and colleagues assessed whether people with HIV who had been cured of HCV experienced the same mortality as individuals with HIV who never had HCV. They matched patients with well-controlled HIV, no cirrhosis, and HCV cure through DAAs started between 2013 and 2020 with up to 10 individuals with virally suppressed HIV monoinfection based on age (±5 years), sex, HIV transmission group, AIDS status, and BMI.
“No other study, at the time we began this research, had explored this question,” Requena says. “We specifically wanted to investigate factors other than hepatic disease that might explain mortality, so we focused on participants without cirrhosis.”
Mortality Risk Increases 12 Months After Cure
The researchers assessed 3,961 patients with HIV who had been cured of HCV (G1) and 33,872 people with HIV and no HCV infection (G2). The median age of participants was 52 and most (77%) were men. Median follow-up was slightly longer in G1 versus G2 (3.7 years vs 3.3 years).
Requena and colleagues reported 150 deaths in G1 (adjusted incidence rate [aIR], 12.2 per 1,000 person years) and 509 deaths in G2 (aIR, 6.3 per 1,000 person years), for an incidence rate ratio (IRR) of 1.9 (95% CI, 1.4-2.7). Despite viral suppression among all participants, people with HIV who had been cured of HCV experienced poorer survival outcomes than those with HIV alone. The elevated risk persisted 12 months after HCV cure (IRR, 2.4; 95% CI, 1.6-3.5), and the most frequent cause of death (n=28) in G1 was non–AIDS/non–liver-related malignancy.
“Among participants with HIV and prior HCV coinfection, the risk for death was significantly higher 12 months after HCV cure, while there was no difference in the first 12 months of follow-up,” Requena says. “When looking at causes of death, there was a persistence of higher liver-related mortality in the HCV-cured population compared with the group with no HCV (17.3% vs 3.9%), despite the absence of clinically detected cirrhosis.”
Univariable analysis showed that showed that people with HIV who were cured of HCV had a greater 5-year probability of death than those with HIV alone (6% vs 2%; Figure).
Directions for Future Research
The findings indicate that, along with “micro-elimination efforts” that use HIV care services to eliminate HCV, surveillance for liver and non-liver-related complications that may lead to mortality is still necessary for individuals with HIV who have been cured of HCV, according to Requena.
She also pointed to ways in which the current findings should be expanded upon. “Studies with a longer follow-up are needed, ones that control for substance use, non-alcoholic steatohepatitis, and liver function alterations,” Requena says. “Furthermore, these results may change in the future with widespread and immediate access to DAAs that prevent long-standing HCV infection and its complications.”
Finally, research that explores the role of tobacco, alcohol, and other substance use in the morbidity and mortality of people living with HIV who have been cured of HCV are needed, “in addition to determining the role of active injection drug use and access to harm reduction services in the mortality of people with HIV and past HCV who use drugs,” she notes.
