Elbasvir and grazoprevir for hepatitis C virus genotype 1 infection in people with recent injecting drug use (DARLO‐C): An open‐label, single‐arm, phase 4, multicentre trial

Abstract

Background and AimsDirect‐acting antiviral therapy for hepatitis C virus (HCV) is effective, but few prospective studies among people with ongoing injecting drug use exist. This study evaluated the efficacy of elbasvir/grazoprevir in people with HCV genotype 1/4 (G1/4) infection and recent injecting drug use. An exploratory aim evaluated the feasibility of fingerstick point‐of‐care HCV RNA testing prior to and following treatment.MethodsDARLO‐C (ClinicalTrials.gov: NCT02940691) is an open‐label phase 4 trial. Participants were recruited between May 2017 and March 2018 from two drug treatment clinics, two hospital clinics, and one community clinic in Australia. Inclusion criteria included recent injection drug use (previous 6 months) and HCV G1/4 infection. Exclusion criteria included prior HCV treatment and decompensated liver disease. Participants received elbasvir/grazoprevir once‐daily for 12 weeks. The primary endpoint was undetectable HCV RNA 12 weeks post‐treatment (SVR). Fingerstick whole‐blood samples were tested using the Xpert HCV Viral Load Fingerstick (Xpert HCV VL Fingerstick) assay and compared to the Aptima HCV Quant Dx Assay on plasma samples.ResultsOf a planned 150 participants, 32 were enrolled due to slower than anticipated recruitment [median age 46 years, 10 (31%) female, 29 (91%) G1a]. Eighteen (56%) were receiving opioid agonist therapy and 29 (91%) injected in the previous month. Twenty‐six (81%) of 32 completed treatment (lost to follow‐up, n = 5; incarceration, n = 1). There were no virological failures. Twenty‐four (75%, 95% CI 59%‐91%) of 32 achieved SVR. Two participants who completed treatment did not have SVR (loss to follow‐up, n = 1; refused test, n = 1). Among paired samples (n = 36), sensitivity of the Xpert HCV VL Fingerstick assay for HCV RNA detection was 100.0% (95% CI 75.3%‐100.0%) and specificity was 95.7% (95% CI 78.1%‐99.9%).ConclusionElbasvir/grazoprevir is effective among people with HCV G1 with recent injecting drug use. Implementation of point‐of‐care HCV RNA testing was feasible, but the high error rate requires investigation.

What Hepatitis C Virus (HCV) Diagnostic Tools Are Needed to Advance Diagnosis of Current HCV Infection in Outreach Settings and in a Nonclinical Setting?

“…The Xpert HCV Viral Load Fingerstick assay and the Xpert HCV Viral Load assay (Cepheid, Sunnyvale, California) both enable diagnosis of active infection by detecting HCV RNA in 1 hour and have a pooled sensitivity and specificity of 98% and 100%, respectively. The test has been used in multiple research and programmatic studies globally [ 31 ], including in Australia [ 33–36 ], Tanzania [ 37 ], Spain [ 38 ], Italy [ 39 ], Switzerland [ 40 ], France [ 41 ], Indonesia [ 42 ], and Cambodia [ 43 ]. Although the Cepheid platform is already used in the US for the diagnosis of other infections [ 44 ], this test is not yet FDA approved.…”

Predictors of engagement in screening for a hepatitis C virus (HCV) treatment trial in a rural Appalachian community

“…20 Studies largely from Australia and Europe reported that people who use drugs infected with HCV can be effectively screened, treated and cured with direct-acting antivirals (DAAs). [21][22][23] In fact, to meet the 2030 HCV elimination goals set forth by WHO, it was suggested that people who use drugs be specifically engaged for treatment to reduce the potential for HCV transmission. 24,25 Treating people who inject drugs makes sense from a public health perspective; if an active person who injects drugs is cured, they will no longer transmit the virus through sharing of infected syringes or other injection paraphernalia.…”

“…Studies largely from Australia and Europe reported that people who use drugs infected with HCV can be effectively screened, treated and cured with direct‐acting antivirals (DAAs) 21–23 . In fact, to meet the 2030 HCV elimination goals set forth by WHO, it was suggested that people who use drugs be specifically engaged for treatment to reduce the potential for HCV transmission 24,25 .…”

Impact of an Accelerated Pretreatment Evaluation on Linkage-to-Care for Hepatitis C-infected Persons Who Inject Drugs

“… 4 - 6 Despite concerns about reinfection risk and nonadherence to HCV treatment, there is some evidence that HCV treatment is effective in this population. 1 , 7 - 10 …”

“…[4][5][6] Despite concerns about reinfection risk and nonadherence to HCV treatment, there is some evidence that HCV treatment is effective in this population. 1,[7][8][9][10] HCV infection is typically diagnosed and assessed in several sequential steps, including antibody (anti-HCV) testing followed by confirmation of the presence of an active infection (HCV RNA), determination of the HCV genotype, and evaluation of liver fibrosis. This approach requires multiple visits, and there is a risk of attrition in between visits.…”