Combo Drug Effective for Some Relapsed HCV Patients

A new study finds that retreating chronic hepatitis C genotype 1 infection with sofosbuvir plus ledipasvir may be effective for patients who relapse after sofosbuvir plus ribavirin.

For their study, a team led by investigators from the University of Maryland and the National Institutes of Health approached patients treated with sofosbuvir plus ribavirin for 24 weeks in the National Institute of Allergy and Infectious Diseases (NIAID) SPARE study who relapsed after treatment. According to the authors, most of the participants were black men with an interleukin-28B non-CC genotype, who were offered retreatment with sofosbuvir plus ledipasvir for 12 weeks in the ongoing, phase IIa, open-label NIAID SYNERGY study. The authors note that 14 of the patients enrolled, and the medication was a single daily tablet of 400 mg of sofosbuvir and 90 mg of ledipasvir.
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All patients achieved sustained viral response to treatment (SVR12), including 7 who had advanced liver disease and 1 with a detectable NS5B S282T mutation, Most adverse events, including loose stool, constipation, headache, myalgia, nasal congestion, and pruritic rash, were mild, according to the authors.

The findings suggest that patients who have experienced viral relapse after sofosbuvir/ribavirin treatment can be successfully retreated with sofosbuvir/ledipasvir for 12 weeks, the authors wrote, noting the low incidence of adverse events, low pill burden, short treatment duration, and high efficacy demonstrated in this group and other populations as factors that “make this drug combination attractive in a real-world setting.”

These findings “were a surprise, because we had several patients with cirrhosis and one with S282T mutation, which confers complete resistance to sofosbuvir in vitro. All of these patients who had risk factors for relapse, achieved SVR12,” says Anita Kohli, MS, MD, a clinician investigator at the National Institutes of Health in Bethesda, Md., and co-author of the study.

This treatment could be the standard of care for patients who have failed sofosbuvir and ribavirin, says Kohli, who notes that the duration between initial treatment failure after sofosbuvir and ribavirin and pretreatment with sofosbuvir and ledipasvir, was over 1 year.

However, “we do not know if patients would have responded in a similar fashion had they been retreated sooner,” she says, adding that “resistance to HCV drugs is an evolving story and seems quite different than with HIV. It will continue to evolve with the introduction of new drugs and drug classes.”

—Mark McGraw

Reference

Osinusi A, Kohli A, et al. Re-treatment of Chroniv HCV Genotype 1 Infection After Relapse. Ann Intern Med. 2014.