Treatment was also successful in patients with prior noncompletion or poor adherence to direct-acting antiviral therapy.
A fixed-dose combination therapy of sofosbuvir, velpatasvir, and voxilaprevir (SOF/VEL/VOX, Vosevi, Gilead) was highly effective after 12 weeks in retreating direct-acting antiviral-experienced patients with hepatitis C virus infection, with and without HIV co-infection, including those with prior noncompletion of treatment or poor adherence, according to results of a new study.
Hepatitis C virus infection can be successfully treated with the use of direct-acting antiviral agents. In rare cases, patients can relapse; however, they can still be retreated successfully. SOF/VEL/VOX is one such treatment for hepatitis C virus infection that has shown success in patients who are treatment-experienced; however, many studies have not assessed the success of retreatment in patients with HIV or hepatitis B virus co-infection.
“I think many people expect that the drugs will work the same in HIV-positive patients as in HIV negative patients because of the early data in ledipasvir/sofosbuvir (Harvoni, Gilead) especially showing similar efficacy like in the ERADICATE study,” study lead investigator Eleanor MP Wilson, MD, MHS, assistant professor of medicine at the University of Maryland School of Medicine in Baltimore, Maryland, explained in an email with MD Magazine®. “[However,] some recent data has shown that in real-world studies, patients with HIV may be less likely to succeed, because of drug interactions, immunologic effects, or other factors. [Therefore,] the newer retreatment regimens need to be tested in people with HIV infection, to show that there are no drug interactions and that patients with HIV and hepatitis C virus [or hepatitis B virus] co-infection will have retreatment options.”
A team of investigators led by Wilson, pulled data from the RESOLVE trial (NCT02745535), an open-label phase 2b study on the safety and efficacy of 12 weeks of a fixed dose of SOF/VEL/VOX (sofosbuvir 400mg/velpatasvir 100mg/voxilaprevir 100mg) in hepatitis C virus-infected patients with early and advanced liver disease, including those with HIV or hepatitis B virus infection, who failed previous combination direct-acting antiviral therapy. The primary endpoint was the proportion of patients who achieve sustained viral response at 12 weeks, as well as the incidence of grade 3 or grade 4 adverse events during treatment or within 30 days of treatment completion.
A total of 77 subjects were enrolled in the study at 3 sites in Baltimore and Washington, DC. The subjects were predominantly male (n = 64, 83%) and black (n = 66, 86%), with a mean age of 60 years (SD 8 years). Three-quarters of the patients (n = 58, 75%) were infected with hepatitis C virus genotype 1a, 17 patients (22%) were HIV-positive, and 2 (3%) were co-infected with HIV and hepatitis B virus.
A little over half of the participants (n = 39, 51%) had previously used intravenous drugs. About 40% (n = 31) had compensated cirrhosis at baseline and 35% (n = 27) had F2 or lower liver fibrosis.
Direct-acting antiviral experience included ledipasvir/sofosbuvir (n = 69, 89%); paritaprevir/ritonavir/ombitasvir plus dasabuvir (n = 3, 4%); elbasvir/grazoprevir (n = 2, 3%); simeprevir/sofosbuvir (n = 2, 3%); sofosbuvir/daclatasvir (n = 1, 1%), while 9 patients (12%) had received other regimens (not listed in the study abstract). A total of 19 patients (25%) had received more than 1 treatment for hepatitis C virus infection, which included 13 patients (17%) who had prior interferon experience and 11 patients (14%) who had experience with more than 1 direct-acting antiviral regimen.
A total of 22 patients (29%) did not complete their previous direct-acting antiviral treatment for reasons that included poor adherence (n = 14, 64%), interruption (n = 4, 18%), lost or stolen medication (n = 2, 9%), or adverse event (n = 1, 5%), according to the study.
Sustained viral response at 12 weeks was achieved by 70 of the 77 patients (90.9%). Of the 22 patients who did not complete their previous treatment with direct-acting antivirals, 18 achieved sustained viral response at 12 weeks. Two patients were awaiting sustained viral response determination and 2 had discontinued treatment early because of intercurrent illness, according to the study authors.
A total of 3 participants (4%) discontinued treatment early for non-SOF/VEL/VOX-related adverse events. These were traumatic subdural hematoma, hypertensive urgency, and colitis. Two patients (3%) were lost to follow up, and 1 patient died because of an unrelated newly diagnosed hepatocellular carcinoma. Furthermore, 1 patient had virologic relapse.
Adverse events that were related to SOF/VEL/VOX were reported by >5% of the participants and included fatigue, headache, diarrhea, abdominal pain, and constipation. Three grade 4 adverse events were reported, but they were determined to be unrelated to the study drug. These included subdural hematoma and new carcinoma diagnoses (squamous cell and hepatocellular).
“Our study shows that SOF/VEL/VOX is a good option, in terms of both safety and efficacy, for retreatment of hepatitis C virus infection in patients with HIV, those with hepatitis B virus infection on treatment, and in those patients who had previously not completed their initial direct-acting antiviral regimen (with either poor adherence or treatment interruption),” Wilson said. “We were able to show high retreatment responses for these traditionally difficult to treat groups, at rates similar to those reported in the registrational studies. It’s important that these traditionally understudied groups have validation that they have options for retreatment, including options that minimize drug interactions and very safe toxicity profiles.”
Looking to the future and next steps, Wilson stated that “we need to continue to show the real-world effectiveness of retreatment [for hepatitis C virus infection] to help further ongoing public health eradication efforts [of the disease].”
The study, “Retreatment with SOF/VEL/VOX in Treatment-Experienced Patients with and without HIV: The Resolve Study,” was presented at the 2018 American Association for the Study of Liver Diseases (AASLD) Liver Meeting, November 9-13, 2018, in San Francisco, California.
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