by Carolyn Chu, MD, MSc, AAHIVS, AAHIVM Chief Medical Officer
December 30, 2025
Featured Literature:
McDonell CC, Assaf R, McKinney J, et al. Assessment of RNA at SVR4 and treatment completion as alternative measures of hepatitis C cure for people who inject drugs. Open Forum Inf Dis. 2025 Dec 19. https://doi.org/10.1093/ofid/ofaf737.
NOW (No One Waits) Study investigators assessed the concordance of SVR12 with SVR4, as well as at treatment completion, in clinical trial participants with a history of injection drug use who received 12 weeks of sofosbuvir/velpatasvir via a community-based, “test and treat” model. Sixty-nine participants who completed the SVR12 study visit were included in this primary analysis: 67% identified as male, median age was 49 years, 83% had injected drugs in the past year, and 55% had slept outside in the past year. Thirty-six (52%) had genotype 1a, 6 (9%) had genotype 1b, 5 (7%) had genotype 2, and 16 (23%) had genotype 3. Five participants (7%) had FIB-4 score greater than 3.25. 27 (39%) completed 90% of the 84-dose regimen and 42 (61%) did not; 6 participants were lost to follow-up. 58 participants (84%) attained SVR12 and 5 did not; in 2 of these 5 cases, HCV RNA detected in the sample collected at the SVR12 visit had a genotype inconsistent with pre-treatment testing (suggesting potential reinfection). The positive predictive value of SVR4 for SVR12 was 100% (38/38) and negative predictive value was 100% (1/1).
Author’s Commentary:
This brief report helps affirm the AASLD’s updated “Hepatitis C Point of Care Test and Treat Algorithm” (released early 2025) that identified SVR4 as an alternative treatment endpoint to measure whether HCV cure was achieved or not among treatment-naïve individuals without cirrhosis. Among NOW Study participants (which included a small number of individuals with genotype 3 and a small number with advanced fibrosis/cirrhosis as indicated by FIB-4) engaged in HCV treatment in a community setting, both the positive predictive value and negative predictive value of HCV RNA measured at treatment completion (EOT) and at SVR4 had strong concordance with SVR12.
Disclaimer: Although employed at the same institution as several of the NOW Study investigators, Dr. Chu was not involved in this research and has no financial relationship with its investigators.
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