ABSTRACT
OBJECTIVES: Chronic hepatitis C-infected patients who do not respond to nonstructural 5A inhibitor-containing regimens have few treatment options. It is unclear if patients who fail glecaprevir/pibrentasvir (G/P) (Mavyret) can be re-treated with sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX) (Vosevi) because the latter's registration trials antedated the availability of the former. METHODS: Adherent virologic failures to G/P were re-treated with 12 weeks of SOF/VEL/VOX, and all subjects underwent resistance testing at baseline and again with subsequent relapse. RESULTS: Ninety-four percent of subjects achieved sustained virologic response with re-treatment, despite 90% of 31 subjects harboring nonstructural 5A inhibitor resistance-associated mutations at baseline. DISCUSSION: SOF/VEL/VOX is an effective regimen for virologic failures to G/P.
Subject(s)
Antiviral Agents/therapeutic use , Carbamates/therapeutic use , Hepatitis C, Chronic/drug therapy , Heterocyclic Compounds, 4 or More Rings/therapeutic use , Macrocyclic Compounds/therapeutic use , Sofosbuvir/therapeutic use , Sulfonamides/therapeutic use , Aminoisobutyric Acids , Benzimidazoles/therapeutic use , Cyclopropanes , Drug Resistance, Viral , Drug Therapy, Combination , Female , Genotype , Hepacivirus/genetics , Humans , Lactams, Macrocyclic , Leucine/analogs & derivatives , Male , Proline/analogs & derivatives , Pyrrolidines , Quinoxalines/therapeutic use , RNA, Viral/blood , Sustained Virologic Response , Treatment Failure , Treatment OutcomeABSTRACT
BACKGROUND & AIMS: The efficacy and safety of interferon-free regimens for the treatment of chronic hepatitis C virus (HCV) infections require further evaluation and comparison with those of interferon-containing regimens. We compared a regimen of peginterferon, ribavirin, and sofosbuvir with a regimen of simeprevir and sofosbuvir in patients with HCV infection and unfavorable treatment features. METHODS: We performed a prospective open-label study of 82 patients with chronic HCV genotype 1a infection and Child's grade A cirrhosis enrolled from 2 clinics at a single center in Atlanta, Georgia, from December 2013 through January 2014. Fifty patients (61%) had not responded to treatment with peginterferon and ribavirin (null responders), and 32 (39%) were therapy naive; 39 (48%) were African American. Subjects were assigned randomly to groups given simeprevir (150 mg/day) and sofosbuvir (400 mg/day) (n = 58 in the final analysis) or peginterferon alfa 2b (1.5 mcg/kg/wk), ribavirin (1000-1200 mg/day), and sofosbuvir (400 mg/day) (n = 24 in the final analysis). Both regimens were given for 12 weeks. The primary trial end point was the proportion of patients with undetectable HCV-RNA levels 12 weeks after therapy completion (SVR12). RESULTS: A significantly greater percentage of patients (93%) given simeprevir and sofosbuvir achieved an SVR12 than those given the interferon-containing regimen (75%) (P = .02). Patients given the interferon-containing regimen had a significantly higher rate of virologic relapse than patients given simeprevir and sofosbuvir (P = .009), as well as worse self-reported outcomes and more side effects. Quality-of-life scores were higher in patients with SVR12 than those without, regardless of treatment regimen. CONCLUSIONS: In a prospective study of patients with chronic HCV genotype 1a infection and cirrhosis (48% African American and 61% prior null responders), a 12-week regimen of simeprevir and sofosbuvir produced a significantly higher rate of SVR12 and was better tolerated, with a lower viral relapse rate, than a 12-week regimen of peginterferon, ribavirin, and sofosbuvir. Clinicaltrials.gov no: NCT021683615.
