title: Concordance of sustained virologic response at weeks 4, 12 and 24 post-treatment of hepatitis c in the era of new oral direct-acting antivirals: A concise review.
abstract: The goal of treatment for chronic hepatitis C viral (HCV) infection is to cure the infection rather than suppress the virus. Historically, a sustained virological response (SVR) defined as undetectable HCV RNA at 24 weeks following the completion of treatment was considered the gold standard to define successful eradication of the virus as a primary endpoint in clinical trials. SVR measured at 12 weeks post-treatment has been shown to be highly concordant with SVR24 in trials of pegylated interferon and ribavirin. The appropriateness and durability of SVR12 as the efficacy endpoint with new oral direct-acting antivirals is less established. A literatura search was performed using PubMed, EMBASE and CENTRAL databases to identify any studies that examined the concordance between SVR24 and earlier time points. Two studies and 4 abstracts were found that performed concordance analyses using positive and negative predictive values. Overall, SVR4 and SVR12 were highly concordant with SVR24 with high positive (> 97%) and negative (> 94%) predictive values; however there was a higher risk of HCV relapse occurring after post-treatment week 4. The majority of the data focused on SVR12 and demonstrated that SVR12 reliably predicted SVR24 in several populations infected with HCV (treatment-naïve, prior null responders, different genotypes) using various new oral direct-acting antiviral regimens. In conclusion, the available data suggests that SVR12 is a reliable assessment of HCV eradication and could be used instead of SVR24 for drug development clinical trials assessing efficacy of new direct-acting antivirals. Data on the long-term durability of SVR12 is still needed.
authors: Faculty of Pharmaceutical Sciences and the Division of Gastroenterology, University of British Columbia, Vancouver, BC, Canada.
authors: Sarah V
authors: SV
authors: Burgess
authors: Faculty of Pharmaceutical Sciences and the Division of Gastroenterology, University of British Columbia, Vancouver, BC, Canada.
authors: Trana
authors: T
authors: Hussaini
authors: Faculty of Pharmaceutical Sciences and the Division of Gastroenterology, University of British Columbia, Vancouver, BC, Canada.
authors: Eric M
authors: EM
authors: Yoshida
mesh_terms: D015081:2-Naphthylamine; D000621:Aminoisobutyric Acids; D000998:Antiviral Agents / Q000627:therapeutic use*; D003521:Cyclopropanes; D004359:Drug Therapy, Combination; D016174:Hepacivirus / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D007372:Interferons / Q000627:therapeutic use; D047029:Lactams, Macrocyclic; D007930:Leucine / Q000031:analogs & derivatives; D047028:Macrocyclic Compounds / Q000627:therapeutic use; D009842:Oligopeptides / Q000627:therapeutic use; D011092:Polyethylene Glycols / Q000627:therapeutic use; D011392:Proline / Q000031:analogs & derivatives; D011804:Quinolines; D012367:RNA, Viral / Q000097:blood*; D012254:Ribavirin / Q000627:therapeutic use; D019438:Ritonavir / Q000627:therapeutic use; D000069474:Sofosbuvir / Q000627:therapeutic use; D013449:Sulfonamides / Q000627:therapeutic use; D000072230:Sustained Virologic Response; D013844:Thiazoles / Q000627:therapeutic use; D013997:Time Factors; D014498:Uracil / Q000031:analogs & derivatives / Q000627:therapeutic use; D019562:Viral Load
chemical_list: D000621:Aminoisobutyric Acids; D000998:Antiviral Agents; D003521:Cyclopropanes; D047029:Lactams, Macrocyclic; D047028:Macrocyclic Compounds; D009842:Oligopeptides; D011804:Quinolines; D012367:RNA, Viral; D013449:Sulfonamides; D013844:Thiazoles; D011092:Polyethylene Glycols; D012254:Ribavirin; D014498:Uracil; D007372:Interferons; C552340:faldaprevir; D011392:Proline; D015081:2-Naphthylamine; C588260:dasabuvir; D007930:Leucine; D019438:Ritonavir; C585405:paritaprevir; D000069474:Sofosbuvir