Win Min Han, Sunil Solomon, Laura Smeaton, Anchalee Avihingsanon, Sandra Wagner-Cardoso, Jiani Li, Aiyappa Parvangada, Mark Sulkowski, Susanna Naggie, Ross Martin, Hongmei Mo, Evguenia Maiorova, David Wyles
{"title":"Reinfection and resistance associated substitutions following a minimal monitoring approach for HCV treatment in MINMON trial.","authors":"Win Min Han, Sunil Solomon, Laura Smeaton, Anchalee Avihingsanon, Sandra Wagner-Cardoso, Jiani Li, Aiyappa Parvangada, Mark Sulkowski, Susanna Naggie, Ross Martin, Hongmei Mo, Evguenia Maiorova, David Wyles","doi":"10.1093/cid/ciae627","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Simplified approaches to HCV treatment delivery are needed to meet elimination goals. However, the impact of low-touch strategies on individuals at higher risk due to treatment failure or reinfection is unknown. We estimated HCV reinfection rates, and the impact of resistance associated substitutions (RASs) on response in the ACTG A5360 (MINMON) trial.</p><p><strong>Methods: </strong>HCV RNA evaluations were scheduled at weeks 0, 24 (sustained viral response [SVR] visit), 48 and 72. Participants with post-entry HCV RNA ≥ lower limit of quantification (LLoQ) had deep sequencing of NS5A and NS5B genes performed. Phylogenetic analysis distinguished between reinfection and treatment failure. Reinfection rates per 100 person-years (PYS) were calculated with 95%CI constructed using Poisson distribution.</p><p><strong>Results: </strong>Of 397 participants with post-entry HCV RNA, 29 had ≥LLoQ and available sequencing data. Of those 29, 5 participants initially designated as non-SVR, and 12 participants initially attaining SVR (evaluated at week-24) were determined to have reinfections (total 17 reinfections) (reinfection rate 3.9/100 PYS [95%CI 2.4-6.2]). All 17 participants with HCV reinfection were male (13 MSM and 15 with HIV). Of 29 had ≥LLoQ, 12 were identified as treatment failure. SVR (excluding reinfections) in presence and absence of baseline RAS was 93.5% (43/46) and 97% (337/346), respectively, with an overall SVR rate of 97.0% [95%CI 94.8-98.3] (385/397).</p><p><strong>Conclusions: </strong>Accounting for reinfections, SVR in MINMON was 97.0% further supporting simplified HCV treatment. No significant difference in SVR was found by baseline velpatasvir RAS. The high reinfection rate, especially among MSM with HIV, underscores the need to scale-up evidence-based interventions to reduce reinfection.</p>","PeriodicalId":10463,"journal":{"name":"Clinical Infectious Diseases","volume":" ","pages":""},"PeriodicalIF":8.2000,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Clinical Infectious Diseases","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1093/cid/ciae627","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Background: Simplified approaches to HCV treatment delivery are needed to meet elimination goals. However, the impact of low-touch strategies on individuals at higher risk due to treatment failure or reinfection is unknown. We estimated HCV reinfection rates, and the impact of resistance associated substitutions (RASs) on response in the ACTG A5360 (MINMON) trial.
Methods: HCV RNA evaluations were scheduled at weeks 0, 24 (sustained viral response [SVR] visit), 48 and 72. Participants with post-entry HCV RNA ≥ lower limit of quantification (LLoQ) had deep sequencing of NS5A and NS5B genes performed. Phylogenetic analysis distinguished between reinfection and treatment failure. Reinfection rates per 100 person-years (PYS) were calculated with 95%CI constructed using Poisson distribution.
Results: Of 397 participants with post-entry HCV RNA, 29 had ≥LLoQ and available sequencing data. Of those 29, 5 participants initially designated as non-SVR, and 12 participants initially attaining SVR (evaluated at week-24) were determined to have reinfections (total 17 reinfections) (reinfection rate 3.9/100 PYS [95%CI 2.4-6.2]). All 17 participants with HCV reinfection were male (13 MSM and 15 with HIV). Of 29 had ≥LLoQ, 12 were identified as treatment failure. SVR (excluding reinfections) in presence and absence of baseline RAS was 93.5% (43/46) and 97% (337/346), respectively, with an overall SVR rate of 97.0% [95%CI 94.8-98.3] (385/397).
Conclusions: Accounting for reinfections, SVR in MINMON was 97.0% further supporting simplified HCV treatment. No significant difference in SVR was found by baseline velpatasvir RAS. The high reinfection rate, especially among MSM with HIV, underscores the need to scale-up evidence-based interventions to reduce reinfection.
期刊介绍:
Clinical Infectious Diseases (CID) is dedicated to publishing original research, reviews, guidelines, and perspectives with the potential to reshape clinical practice, providing clinicians with valuable insights for patient care. CID comprehensively addresses the clinical presentation, diagnosis, treatment, and prevention of a wide spectrum of infectious diseases. The journal places a high priority on the assessment of current and innovative treatments, microbiology, immunology, and policies, ensuring relevance to patient care in its commitment to advancing the field of infectious diseases.