SOF/VEL Treatment Benefits Vulnerable Inner City-Residents With HCV

Vulnerable inner-city residents with hepatitis C (HCV) and high-risk non-medical determinants of health greatly benefitted from a multidisciplinary program of care including Sofosbuvir/Velpatasvir (S/V) treatment.1

“The combination of S/V is approved for the treatment of chronic HCV infection. In registrational trials, cure rates of 95% or more were achieved when administered as one pill per day for a period of 12 weeks, regardless of genotype or disease stage. There is a need to develop and evaluate systems of care in populations excluded from clinical trials,” lead investigator Brian Conway, MD, Vancouver Infectious Diseases Centre, and Simon Fraser University, Vancouver, British Columbia, Canada, and colleagues wrote.1

Conway and colleagues sought to evaluate the safety and efficacy of S/V in a prospective study of inner-city residents with HCV enriched for risk behaviors for non-adherence to therapy, including problematic drug use and unstable housing. The investigators held dedicated outreach events and identified people with HCV who were not currently engaged in health care and who were eligible to receive government-funded antiviral treatment for HCV infection to enroll in the multidisciplinary program. The program was designed to address medical, psychological, social, and addiction-related needs along with providing S/V therapy with enhanced supervision of adherence.

Overall, the program identified 222 eligible participants who were 31.5% female and had a median age of 47 (range, 24–81). Most had HCV genotype 1 (48.2%), followed by 3 (38.7%) , and 21.2% scored F3-F4 FibroScan scores. In looking at non-medical determinants of health, 55.9% have unstable housing, and 98.6% are active drug users, with the majority utilizing fentanyl (82.9%), followed by amphetamines (64.9%).

The investigators initiated S/V treatment in all 222 participants within a median of 6 weeks of engagement in care. Altogether, 218 participants completed treatment, 1 withdrew from the treatment, and 3 died due to overdose. Conway and colleagues found that HCV cure was documented in 211/218 (96.8%), with virologic relapse documented in the other 7 cases (3.2%). The intent-to-treat sustained virologic response (SVR) rate of HCV treatment with S/V was 211/222 (95.0%).

The S/V combination was approved under the name Epclusa for adults with chronic HCV both with and without cirrhosis in August 2016 and later for children with HCV in 2020. It was the first to treat all 6 major genotypes of HCV and thus has a benefit in treating wider swaths of patients in disadvantaged circumstances.2,3 Following S/V’s approval was glecaprevir/pibrentasvir (G/P), approved under the name Mavyret in 2017.4

Other recent research done with S/V in people with HCV last year found that combination sofosbuvir, velpatasvir, and voxilaprevir (SOF/VEL/VOX) was a safe and effective rescue therapy for patients with HCV who previously failed S/V and GLE/PIB.5

Among a cohort of more than 100 patients who completed SOF/VEL/VOX therapy and 12 weeks of follow-up, 88.6% achieved SVR. Although there was a trend toward lower SVR in patients with genotype 3 HCV infection, cirrhosis, and first-line therapy with S/V these associations did not reach statistical significance.5

In total, 142 patients were included in the present study, 100 (70.4%) of whom had failed SOF/VEL and the remaining 42 (29.6%) GLE/PIB. Patients were mainly male (84.5%), White (93.9%), with HCV genotype 3 (49.6%) and liver cirrhosis (47.2%). Among the cohort, 132 patients successfully completed SOF/VEL/VOX therapy, allowing for SVR evaluation. By intention to treat analysis, the SVR rate was 82.4% (117/142). However, investigators pointed out in per protocol analysis, the SVR rate was 88.6% (117/132), noting 11.4% (n = 15) did not respond to SOF/VEL/VOX despite completing treatment with optimal adherence.5

Investigators observed that patients who did not achieve SVR after SOF/VEL/VOX were mainly male (80%), White (92.3%), 11 had previously received SOF/VEL, 9 had genotype 3 infection, and 8 had cirrhosis. However, upon analysis, there were no significant differences in SVR rates according to initial DAA treatment (SOF/VEL 87.9% vs GLE/PIB 90.2%; P = .8), cirrhosis (no cirrhosis 90% vs cirrhosis 87.1%; P = .6) or genotype 3 infection (non-genotype 3 91.9% vs genotype 3 85.5%; P = .3).5

“Our results provide evidence that SOF/VEL/VOX is an effective and safe rescue therapy for patients with HCV infection and nonresponse to SOF/VEL or GLE/PIB,” investigators concluded.5

REFERENCES

1. Conway B, Yi S, Truong D. CHIME: Sofosbuvir/Velpatasvir (S/V) for the Treatment of HCV Infection Among Vulnerable Inner‐City Residents. Journal of Viral Hepatitis. 2025;32(8). doi: 10.1111/jvh.70057

2. FDA Approves Sofosbuvir/Velpatasvir for Treatment of Chronic Hepatitis C Virus Infection. ASCO Post. August 10, 2016. https://ascopost.com/issues/august-10-2016/fda-approves-sofosbuvirvelpatasvir-for-treatment-of-chronic-hepatitis-c-virus-infection/?platform=hootsuite

3. Rosenfeld S. FDA Approves Combination Therapy For Children With HCV. ContagionLive. March 19, 2020. https://www.contagionlive.com/view/fda-approves-combination-therapy-for-children-with-hcv

4. Mavyret FDA Approval History. Drugs.com. Updated June 13, 2025. https://www.drugs.com/history/mavyret.html

5. Ruiz-Cobo JC, Llaneras J, Forns X, et al. Real-life effectiveness of sofosbuvir/velpatasvir/voxilaprevir in hepatitis C patients previously treated with sofosbuvir/velpatasvir or glecaprevir/pibrentasvir. Alimentary Pharmacology and Therapeutics. https://doi.org/10.1111/apt.18020