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Efficacy of ultra-short, response-guided sofosbuvir and daclatasvir therapy for hepatitis C in a single-arm mechanistic pilot study

eLife, 2023-01, Vol.12 [Peer Reviewed Journal]

2023, Flower et al. ;2023, Flower et al. This work is published under https://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. ;2023, Flower et al 2023 Flower et al ;ISSN: 2050-084X ;EISSN: 2050-084X ;DOI: 10.7554/eLife.81801 ;PMID: 36622106

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Title:
Efficacy of ultra-short, response-guided sofosbuvir and daclatasvir therapy for hepatitis C in a single-arm mechanistic pilot study
Author: Flower, Barnaby ; Hung, Le Manh ; Mccabe, Leanne ; Ansari, M Azim ; Le Ngoc, Chau ; Vo Thi, Thu ; Vu Thi Kim, Hang ; Nguyen Thi Ngoc, Phuong ; Phuong, Le Thanh ; Quang, Vo Minh ; Dang Trong, Thuan ; Le Thi, Thao ; Nguyen Bao, Tran ; Kingsley, Cherry ; Smith, David ; Hoglund, Richard M ; Tarning, Joel ; Kestelyn, Evelyne ; Pett, Sarah L ; van Doorn, Rogier ; Van Nuil, Jennifer Ilo ; Turner, Hugo ; Thwaites, Guy E ; Barnes, Eleanor ; Rahman, Motiur ; Walker, Ann Sarah ; Day, Jeremy N ; Chau, Nguyen V V ; Cooke, Graham S
Subjects: Adult ; Antiviral Agents ; Antiviral drugs ; Body mass index ; daclatasvir ; Drug resistance ; Drug Therapy, Combination ; Failure ; Genotype ; Genotype & phenotype ; genotype 6 ; Genotypes ; Hepacivirus - genetics ; Hepatitis C ; Hepatitis C, Chronic - drug therapy ; Humans ; Hypotheses ; Infections ; Interferon ; Interleukins - genetics ; Liver diseases ; Medical research ; Medicine ; Microbiology and Infectious Disease ; Pharmacokinetics ; Pilot Projects ; Polymorphism ; response guided therapy ; Ribavirin - therapeutic use ; sofosbuvir ; Sofosbuvir - therapeutic use ; Treatment Outcome
Is Part Of: eLife, 2023-01, Vol.12
Description: World Health Organization has called for research into predictive factors for selecting persons who could be successfully treated with shorter durations of direct-acting antiviral (DAA) 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. 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-week 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 days 0 and 28. Of 52 adults enrolled, 34 received 4 weeks SOF/DCV, 17 got 8 weeks and 1 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 37 days). Despite a high prevalence of putative NS5A-inhibitor resistance-associated substitutions (RASs), all first-line treatment failures cured after retreatment (13/13). We found no evidence treatment failure was associated with host IFNL4 genotype, viral subtype, baseline RAS, SOF or DCV levels. Shortened SOF/DCV therapy, with retreatment if needed, reduces DAA use in patients with mild liver disease, while maintaining high cure rates. D2 virologic response alone does not adequately predict SVR12 with 4-week treatment. Funded by the Medical Research Council (Grant MR/P025064/1) and The Global Challenges Research 70 Fund (Wellcome Trust Grant 206/296/Z/17/Z).
Publisher: England: eLife Sciences Publications Ltd
Language: English
Identifier: ISSN: 2050-084X
EISSN: 2050-084X
DOI: 10.7554/eLife.81801
PMID: 36622106
Source: Open Access: PubMed Central
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Efficacy of ultra-short, response-guided sofosbuvir and daclatasvir therapy for hepatitis C in a single-arm mechanistic pilot study

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