Skip to main content
Dryad

Ultra-short response-guided Hepatitis C treatment with sofosbuvir and daclatasvir: the SEARCH study HCV sequence data

Data files

Aug 24, 2022 version files 707.74 KB

Abstract

Background

WHO has called for research into predictive factors for selecting persons who could be successfully treated with shorter durations of antiviral therapy for Hepatitis C. We evaluated early virological response as a means of shortening treatment and explored host, viral and pharmacokinetic contributors to treatment outcome.

Methods

Duration of sofosbuvir and daclatasvir (SOF/DCV) was determined according to day 2 (D2) virologic response for HCV genotype (gt) 1- or 6-infected adults in Vietnam with mild liver disease. Participants received 4 or 8 weeks of treatment according to whether D2 HCV RNA was above or below 500 IU/ml (standard duration is 12 weeks). Primary endpoint was sustained virological response (SVR12). Those failing therapy were retreated with 12 weeks SOF/DCV. Host IFNL4 genotype and viral sequencing was performed at baseline, with repeat viral sequencing if virological rebound was observed. Levels of SOF, its inactive metabolite GS-331007 and DCV were measured on day 0 and 28.

Findings

Of 52 adults enrolled, 34 received 4 weeks SOF/DCV, 17 got 8 weeks and one withdrew. SVR12 was achieved in 21/34 (62%) treated for 4 weeks, and 17/17 (100%) treated for 8 weeks. Overall, 38/51 (75%) were cured with first-line treatment (mean duration of 37 days). Despite a high prevalence of putative NS5A-inhibitor resistance-associated substitutions (RAS), all first-line treatment failures were cured after retreatment (13/13). We found no evidence treatment failure was associated with host IFNL4 genotype, viral subtype, baseline RAS or DCV levels. SOF metabolite levels were higher in those failing 4-week therapy.

Interpretation

Shortened SOF/DCV therapy with retreatment if needed, reduces DAA use while maintaining high cure rates. D2 virologic response alone does not adequately predict SVR12 with 4 weeks of treatment.