BACKGROUND: Identifying individuals with hepatitis C virus (HCV) infection who could be cured with a shorter duration of direct-acting antivirals (DAA) therapy would support the effort to reach HCV elimination goals. To date, clinical studies of short duration DAA therapy based on early (e.g., days 2 or 7) HCV RNA levels (e.g., <500 IU/ml) have used arbitrary timepoints and viral load thresholds and yielded suboptimal cure rates. METHODS: A database of HCV-host parameters was built based on mathematically modeling time to cure in about 300 individuals with recent (duration <12 months) or chronic infection treated with DAAs. 200,000 parameter combinations of viral-host and treatment parameters were generated, each representing an in-silico HCV patient under DAA treatment. RESULTS: We assessed response-guided treatment (RGT) strategies based on whether HCV RNA was undetectable on day 7 or day 14 on-treatment. The analysis predicted that treatment duration could be shortened to 5 or 7 weeks for people with recent or chronic infection who have undetectable HCV RNA at day 7 or day 14 of treatment, respectively. CONCLUSIONS: Modeling suggested that most people with recent or chronic HCV treated with DAAs will have undetectable HCV RNA by day 7 or 14 andcould have their treatment duration reduced to 5 or 7 weeks. This modeling-independent RGT approach could improve treatment access, facilitate HCV elimination, and reduce cost, particularly in key populations most affected by HCV, such as people who inject drugs.
Goyal et al. (2026) studied this question.