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High HCV SVR in Rural US Group With
Heavy Use of Opioids, Other Drugs
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AASLD-The Liver Meeting, November 4-8, 2022, Washington, DC
Mark Mascolini
Early results of an ongoing trial in a rural Kentucky county indicate that most HCV-positive drug injectors-many of them being treated for opioid use disorder-will consent to 12-week sofosbuvir/velpatasvir, complete treatment, and attain a sustained virologic response (SVR) [1]. Treatment for opioid use disorder did not predict anti-HCV treatment completion or SVR.
University of Kentucky researchers are conducting the Kentucky Viral Hepatitis Treatment Project (KeY Treat) [2,3] in an attempt to eliminate HCV infection from a rural Kentucky county struggling with an HCV-opioid syndemic. They aim to enroll and treat 400 current and former drug users and other marginalized people regardless of insurance status. KeY Treat provides all care and medications at no cost to participants.
This single-arm, open-label, phase 4 trial recruits Perry County residents at least 18 years old with detectable HCV RNA, aiming to treat them with 12 weeks of sofosbuvir/velpatasvir 400/100 mg [2]. Participants with lab-confirmed lack of immunity to hepatitis A and hepatitis B receive HAV and HBV vaccines.
After an initial phone screen to verify age and residence, the first in-person visit tests people for anti-HCV antibodies and, if positive, for HCV RNA. People with no contraindications get a 2-week supply of sofosbuvir/velpatasvir. In subsequent weeks they return for the rest of their antiviral course, viral load assays, and counseling on drug side effects and risk behaviors. At week 12, when treatment should be completed, participants get another viral load assay and counseling. Viral load is measured once more at week 24 to see if participants have achieved SVR.
Phone screeners called 901 rural residents; only 69 did not meet initial eligibility criteria. Of 832 initially eligible people, 640 (77%) came for an in-person screen. Slightly more than half, 54%, met in-person eligibility criteria and agreed to enter the study. To date, the trial includes 347 people. Among people who agreed to participate, 87% took their first dose at this first visit. Only 10 people (3%) agreeing to treatment never began therapy, leaving a treated population of 337 analyzed in this presentation.
Of these 337 people, median age stood at 41 years, 97% were white, 41.7% women, 97.3% ever used drugs, and 41.1% currently used drugs, usually methamphetamine (58.4%) and prescription opioids (58.4%). One quarter of the study group (24.9%) currently injected drugs, again usually methamphetamine (71.4%) and prescription opioids (42.2%). Median HCV RNA stood at 747,000 IU/L (interquartile range 187,000 to 3,300,000).
Three quarters of participants who began treatment (77.1%) completed the 12-week course. While a smaller proportion of current drug injectors than noninjectors completed treatment (65% vs 80.7%, P = 0.006 after adjustment for demographic and clinical factors), that two thirds completion rate in a challenged, rural injecting population indicates the soundness of the trial plan (and assuredly the commitment of participants and staff).
In an analysis of 312 participants, the only variable that independently predicted completing treatment was injecting drugs, which halved odds of completion (adjusted odds ratio [aOR] 0.48, 95% confidence interval [CI] 0.26 to 0.87). In this analysis, gender, age, white race, and treatment for opioid use disorder did not predict sofosbuvir/velpatasvir completion.
About two thirds of these 337 people attained SVR, while about 20% were lost to follow-up. Nineteen participants (5.6%) died, and another small proportion was still on treatment. Fewer than 5% completed treatment and did not achieve SVR, and half of them resumed therapy and had an undetectable HCV load at their latest visit. Thirty people (44%) lost to follow-up had an undetectable viral load at their last visit. Multivariable analysis could isolate no independent predictors of loss to follow-up, including age, race/ethnicity, gender, and current drug use. Staff used phone calls, text messages, and facebook messages to limit loss to follow-up.
Analysis of 227 participants found three independent predictors of SVR: older age in years (aOR 1.13, 95% CI 1.02 to 1.27), number of pills given (a measure of adherence; aOR 1.04, 95% CI 1.00 to 1.09), and injecting drugs (aOR 0.09, 95% CI 0.05 to 2.18; meaning drug injecting cuts chances of SVR about 90%). But the researchers again stressed that two thirds of drug injectors who started sofosbuvir/velpatasvir attained SVR.
The investigators also suggested that COVID could have affected several aspects of the study, including recruitment, loss to follow-up, and failure to attain SVR because at its peaks the pandemic put a halt to recruitment and follow-up several times during the course of this study. To date KeY Treat has cured 221 of about 26,000 Perry County residents of HCV infection.
References
1. Havens J, Schaninger T, Lofwall M, et al. The Kentucky viral hepatitis treatment project (KeY Treat): preliminary outcomes from a phase 4 clinical trial in rural Appalachia. AASLD-The Liver Meeting, November 4-8, 2022, Washington, DC. Abstract 1244.
2. ClinicalTrials.gov. The Kentucky Viral Hepatitis Treatment Study (KeY Treat). ClinicalTrials.gov identifier NCT03949764. https://clinicaltrials.gov/ct2/show/NCT03949764
3. Havens JR, Schaninger T, Fraser H, et al. Eliminating hepatitis C in a rural Appalachian county: protocol for the Kentucky Viral Hepatitis Treatment Study (KeY Treat), a phase IV, single-arm, open-label trial of sofosbuvir/velpatasvir for the treatment of hepatitis C. BMJ Open. 2021;11:e041490. doi: 10.1136/bmjopen-2020-041490. https://bmjopen.bmj.com/content/11/7/e041490.long
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