Shorter Duration of Sovaldi Regimen Deemed Ineffective in Hepatitis C

Six-week direct-acting antiviral treatment regimen with Sovaldi and ribavirin produced sub-optimal results in newly infected hepatitis C patients.

Findings from a phase 2 study revealed that short-term treatment with sofosbuvir (Sovaldi) and ribavirin were ineffective in patients recently infected with hepatitis C virus (HCV).

It has been demonstrated that a 12- to 24-week treatment regimen with Sovaldi and ribavirin is both safe and well tolerated in patients with chronic HCV. In a new study published in Hepatology, researchers wanted to assess the efficacy of the combination for 6 weeks in newly-infected HCV patients.

The open-label study enrolled adults with recent HCV, defined as less than 12 months, who were given 400-mg sofosbuvir daily and weight-based ribavirin (<75kg: 1000mg/day; ≥75kg: 1200mg/day) for 6 weeks. At baseline, the median HCV RNA was 5.4 log10 IU/mL (IQR 4.4-6.8), and the median estimated duration of infection was 37 weeks (IQR 27-41).

The primary efficacy endpoint was sustained virologic response at week 12 post-treatment (SVR12).

Nineteen study participants started treatment with sofosbuvir and ribavirin, with 89% of the participants being male, 74% with HIV, and 68% with HCV genotype 1a. Four participants reported a symptomatic HCV seroconversion illness, including 2 patients with jaundice.

The results of the study showed that at the end of treatment, HCV RNA was non-quantifiable in 89% (n=17) of participants. SVR4 and SVR12 were 42% (n=8) and 32% (n=6), respectively.

Failed treatment was due to post-treatment relapse (n=6), non-response (n=2), reinfection (n=1), and loss to follow up (n=1). SVR12 was related to baseline HCV RNA (≤6 log10 IU/mL, p=0.018), and early on treatment viral kinetics (HCV RNA below the level of quantitation at week 1, p=0.003).

The treatment was found to be well tolerated in study participants, and there was only minimal hematological toxicity observed.

“Baseline HCV RNA … and subsequent rapid viral suppression … were associated with SVR12, which supports further research with more potent DAA regimens in recent HCV infection,” researchers said. “In this cohort, while those participants achieving SVR12 did have significantly lower HCV RNA at baseline, spontaneous clearance was unlikely given the median duration of HCV infection of 37 weeks.”

The findings revealed that 6 weeks of sofosbuvir and ribavirin were safe and well-tolerated, however, the efficacy was sub-optimal. The authors noted that more research needs to be done to determine if more portent inferno-free DAA regimens could allow treatment duration to be shortened in patients with recent, predominately asymptomatic, HCV infection.

“Adherence to therapy was high, by pill count and self-reported questionnaire,” said study author Marianne Martinello, MBBS, FRACP. “Consistent with self-reported adherence, when sampled, all participants had detectable ribavirin plasma concentrations on treatment. The potential for broad access to highly effective, well tolerated [interferon-free] DAA regimens has stimulated discussion around HCV treatment-as-prevention and subsequent HCV elimination. This study conclusively demonstrates that while on-treatment virological suppression was achieved in the majority, a high proportion of participants demonstrated post-treatment relapse.”