Kris V Kowdley1, David R Nelson2, Jacob P Lalezari3, Terry Box4, Norman Gitlin5, Gary Poleynard6, Mordechai Rabinovitz7, Natarajan Ravendhran8, Aasim M Sheikh9, Asma Siddique10, Rafia Bhore11, Stephanie Noviello11, Khurram Rana12. 1. Swedish Medical Center, Seattle, WA, USA. kris.kowdley@swedish.org. 2. University of Florida, Gainesville, FL, USA. 3. Quest Clinical Research, San Francisco, CA, USA. 4. Clinical Research Centers of America, LLC, Murray, UT, USA. 5. Atlanta Gastroenterology Associates, Atlanta, GA, USA. 6. Digestive Health Specialists, Winston-Salem, NC, USA. 7. University of Pittsburgh, Pittsburgh, PA, USA. 8. Digestive Disease Associates, Baltimore, MD, USA. 9. Gastrointestinal Specialists of Georgia, Marietta, GA, USA. 10. Virginia Mason Medical Center, Seattle, WA, USA. 11. Bristol-Myers Squibb Research and Development, Princeton, NJ, USA. 12. Bristol-Myers Squibb Research and Development, Wallingford, CT, USA.
Abstract
BACKGROUND AND AIMS: Many currently available direct-acting antiviral (DAA) regimens are less effective against HCV genotype 3 than against other HCV genotypes. The all-oral, pangenotypic DAA combination of daclatasvir (NS5A inhibitor) + sofosbuvir (nucleotide NS5B inhibitor) was studied in genotype 3-infected treatment-naive and -experienced patients (ALLY-3) who achieved rates of sustained virological response at post-treatment Week 12 (SVR12) of 90 and 86% respectively. In this analysis, we assessed whether on-treatment responses to daclatasvir + sofosbuvir in genotype 3-infected patients could predict treatment outcome. METHODS: In ALLY-3, treatment-naive and -experienced patients, with or without cirrhosis, were treated with daclatasvir + sofosbuvir for 12 weeks. HCV RNA kinetics and categorical virological responses on treatment were assessed. The proportions of responders and nonresponders by study week, and time to first undetectable HCV RNA, were analysed for utility in predicting treatment outcome. RESULTS: Overall, HCV RNA levels declined rapidly during Week 1 of treatment in both treatment-naive and -experienced cohorts. Although patients with cirrhosis had a slower initial virological response as measured by the proportion of patients with HCV RNA below the lower limit of quantification at Week 1, responses converged thereafter. Positive and negative predictive values calculated for on-treatment responses were generally comparable with the overall SVR12 rate and were therefore limited indicators of outcome. SVR12 rates were not impacted by time to first undetectable HCV RNA. CONCLUSIONS: On-treatment responses are not useful predictors of ultimate virological response to the daclatasvir + sofosbuvir regimen.
BACKGROUND AND AIMS: Many currently available direct-acting antiviral (DAA) regimens are less effective against HCV genotype 3 than against other HCV genotypes. The all-oral, pangenotypic DAA combination of daclatasvir (NS5A inhibitor) + sofosbuvir (nucleotide NS5B inhibitor) was studied in genotype 3-infected treatment-naive and -experienced patients (ALLY-3) who achieved rates of sustained virological response at post-treatment Week 12 (SVR12) of 90 and 86% respectively. In this analysis, we assessed whether on-treatment responses to daclatasvir + sofosbuvir in genotype 3-infected patients could predict treatment outcome. METHODS: In ALLY-3, treatment-naive and -experienced patients, with or without cirrhosis, were treated with daclatasvir + sofosbuvir for 12 weeks. HCV RNA kinetics and categorical virological responses on treatment were assessed. The proportions of responders and nonresponders by study week, and time to first undetectable HCV RNA, were analysed for utility in predicting treatment outcome. RESULTS: Overall, HCV RNA levels declined rapidly during Week 1 of treatment in both treatment-naive and -experienced cohorts. Although patients with cirrhosis had a slower initial virological response as measured by the proportion of patients with HCV RNA below the lower limit of quantification at Week 1, responses converged thereafter. Positive and negative predictive values calculated for on-treatment responses were generally comparable with the overall SVR12 rate and were therefore limited indicators of outcome. SVR12 rates were not impacted by time to first undetectable HCV RNA. CONCLUSIONS: On-treatment responses are not useful predictors of ultimate virological response to the daclatasvir + sofosbuvir regimen.
Authors: Michael J Zoratti; Ayesha Siddiqua; Rita E Morassut; Dena Zeraatkar; Roger Chou; Judith van Holten; Feng Xie; Eric Druyts Journal: EClinicalMedicine Date: 2020-01-05
Authors: Ashwin Balagopal; Laura M Smeaton; Jeffrey Quinn; Charles S Venuto; Gene D Morse; Vincent Vu; Beverly Alston-Smith; Daniel E Cohen; Jorge L Santana-Bagur; Donald D Anthony; Mark S Sulkowski; David L Wyles; Andrew H Talal Journal: J Infect Dis Date: 2020-07-23 Impact factor: 7.759