Modeling predicts shortening of DAA treatment duration to 5 weeks in individuals with recent or chronic infection with HCV RNA negativity at day 7 on treatment.

Abstract

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.