A regimen of sofosbuvir-velpatasvir for 12 weeks is safe and efficacious for patients with chronic hepatitis C virus (HCV) genotype 4 infection, according to a study in The Lancet Gastroenterology & Hepatology.
The Simplifying Hepatitis C Antiviral Treatment in Rwanda for Elsewhere in the Developing World (SHARED-3) trial (ClinicalTrials.gov Identifier: NCT03888729) included 2 single-arm, prospective studies. The current findings are from the first study, which assessed the efficacy and safety of sofosbuvir-velpatasvir in adults with chronic HCV infection in Rwanda who had not previously received direct-acting antiviral treatment.
Hospitals with HCV treatment programs throughout Rwanda referred patients after confirmation of active HCV infection by polymerase chain reaction detection of HCV RNA. Eligible participants were aged 18 years and older with a plasma HCV RNA titer of 1000 IU/mL or higher.
Study participants received an oral fixed-dose combination tablet of 400 mg sofosbuvir and 100 mg velpatasvir once daily for 12 weeks. The primary efficacy outcome was the quantity of patients in the intention-to-treat population with sustained virological response (SVR) 12, defined as lacking quantifiable plasma HCV RNA at 12 weeks after completion. The primary safety outcome was the quantity of patients with grade 3 or 4 events or prematurely discontinuing the study drug as a result of an adverse event.
A total of 61 patients were enrolled from September 23, 2019, to January 10, 2020, and follow-up was completed on August 28, 2020. Participants had a median age of 64 (IQR, 51-74) years, and 66% were women. Their median baseline HCV viral load was 5.7 log10 IU/mL (5.2-6.2).
Genotype subtype was determined on baseline isolates for 95% of participants, and all had genotype 4 HCV. The predominant subtypes were 4k (46%), 4r (18%), and 4v (13%). The remainder included 4b, 4c, 4l, 4q, and 1 unknown genotype 4 subtype. A total of 3 isolates could not be sequenced and were considered an indeterminate genotype.
Among the 90% of isolates that were successfully sequenced, each had at least 2 NS5A resistance-associated substitutions.
Researchers found SVR12 in 59 (97% [95% CI, 89-99]) participants, and 60 (98%) participants had an HCV RNA titer less than the lower limit of detection (15 IU/mL) after treatment. The proportion of participants who had SVR12 was 100% for all genotype subtypes, except for 4k (96%) and 4r (91%). SVR12 was achieved by 98% of participants with 2 baseline NS5A resistance-associated substitutions and in 92% of participants with 3 or more baseline NS5A resistance-associated substitutions.
Among 18 participants, 21 grade 3 adverse events were reported, of which 4 were serious. Hypertension (20%) was the most common grade 3 adverse event. No grade 4 adverse events or deaths occurred.
The investigators noted that the extent of liver fibrosis was assessed using the noninvasive tests aspartate aminotransferase-to-platelet ratio index and fibrosis-4 index tests, which are not as accurate as transient elastography or liver biopsy for detecting cirrhosis. Also, few participants with HIV co-infection participated, and the study was not powered to detect statistically significant differences in efficacy between genotype subtypes.
“Our study suggests sofosbuvir-velpatasvir could be effective for optimizing clinical outcomes for HCV treatment programs in regions with substantial proportions of individuals with HCV genotype 4 subtypes with high numbers of baseline resistance-associated substitutions where genotype subtype determination or viral sequencing are not possible, affordable, or readily available,” the researchers noted.
Disclosure: This research was supported by Gilead Sciences. One of the study authors declared an affiliation with a biotech company. Please see the original reference for a full list of disclosures.
Kateera F, Shumbusho F, Manirambona L, et al. Safety and efficacy of sofosbuvir-velpatasvir to treat chronic hepatitis C virus infection in treatment-naive patients in Rwanda (SHARED-3): a single-arm trial. Lancet Gastroenterol Hepatol. Published online March 3, 2022. doi:10.1016/S2468-1253(21)00398-8