Measurements for HCV Cure Could Be Done Earlier Among People Who Inject Drugs
People with hepatitis C virus who inject drugs could be evaluated for cure approximately 2 months earlier than current standards call for.
In a sample of nearly 70 individuals, researchers observed perfect concordance for HCV RNA viral load 4 weeks after treatment completion compared with 12 weeks. They also found measurements as soon as treatment concluded nearly matched that at 12 weeks.
“These results support current efforts to apply SVR4 [sustained virologic response at 4 weeks after treatment] as an alternative endpoint for uncomplicated cases of HCV and highlight why treatment completion may also be seen as a reasonable endpoint in some contexts,” lead author Claire C. McDonell, MS, PhD student in the department of epidemiology and biostatistics at University of California, San Francisco, and colleagues wrote.
Updated guidelines
More than 95% of people with HCV who complete treatment with direct-acting antivirals are cured, according to study background.
The current standard for determining cure is measuring HCV RNA viral load 12 or more weeks after treatment completion (SVR12).
SVR4 has been included in updated clinical guidelines as an alternative cure measurement for patients who do not have cirrhosis or have not received DAAs.
“This measure of cure was updated based on high levels of loss to follow-up between treatment completion and SVR12, as well as high concordance between HCV RNA viral load testing at SVR4 and SVR12 among participants of randomized clinical trials and drug development programs,” McDonell and colleagues wrote.
However, people who inject drugs often are not included in clinical trials.
McDonell and colleagues investigated whether SVR4 could be used as an alternative measure for this population, too.
They included 69 adults (median age, 49 years; interquartile range, 41-59; 67% men; 57% white) from the No One Waits trial, a nonrandomized study that evaluated the effectiveness of starting HCV treatment where people got diagnosed. The study included only those who self-reported lifetime injection drug use.
Analysis included participants who finished their SVR12 visit.
Most (97%) lived below the national poverty line and 83% had injected drugs in the previous year.
Concordance between SVR4 and SVR12 served as the primary endpoint.
An ‘alternative’ clinical endpoint
Overall, 84% of participants achieved SVR12.
RNA viral load at treatment completion had a positive predictive value for SVR12 of 96.6% and negative predictive value of 100%.
Tests at SVR4 had positive and negative predictive values for SVR12 of 100%.
“These findings support the use of SVR4 as an alternative clinical endpoint,” McDonell and colleagues wrote.
“Importantly, our study provides critical insight into the real-world experiences of a population historically underrepresented in data used to guide clinical updates,” they added.
Researchers acknowledged study limitations, including the small sample size.
“Our results also suggest that HCV RNA at treatment completion may be an informative alternative outcome in uncomplicated cases,” they wrote. “Adoption of treatment completion as an alternative endpoint could reduce loss to follow-up, particularly among patients less engaged with the health care system. However, concerns remain about relapse after treatment completion or patients whose viral load does not completely disappear until immediately after treatment completion. Both patient types would be misclassified if treatment completion were used as an alternative endpoint.
“While our results support the feasibility of shorter treatment timelines, they do not diminish the necessity of ongoing HCV testing for new HCV infections in high-risk populations. Any updates to alternative clinical endpoints should be incorporated into existing testing guidelines, which suggest regular testing for those at high risk,” McDonell and colleagues wrote.
By Josh Friedman
Reference: McDonell CC, et al. Open Forum Infect Dis. 2025; doi:10.1093/ofid/ofaf737.
Source: Healio