Patient-centred models of hepatitis C treatment for people who inject drugs: a multicentre, pragmatic randomised trial

Alain H Litwin¹, Paula J Lum², Lynn E Taylor³, Shruti H Mehta⁴, Judith I Tsui⁵, Judith Feinberg⁶, Arthur Y Kim⁷, Brianna L Norton⁸, Moonseong Heo⁹, Julia Arnsten⁸, Paul Meissner¹⁰, Alison Karasz¹¹, M Diane Mckee¹¹, John W Ward¹², Nirah Johnson¹³, Irene Pericot-Valverde¹⁴, Linda Agyemang⁸, Ellen S Stein², Aurielle Thomas¹⁵, Courtney Borsuk⁴, Kendra L Blalock⁵, Samuel Wilkinson¹⁶, Katherine Wagner¹⁷, Jillian Roche⁷, Cristina Murray-Krezan¹⁸, Jessica Anderson¹⁷, Vanessa Jacobsohn¹⁹, Anne F Luetkemeyer², Oluwaseun Falade-Nwulia²⁰, Kimberly Page¹⁷; HERO Study Group

Affiliations

¹ School of Health Research, Clemson University, Clemson, SC, USA; Department of Medicine, University of South Carolina School of Medicine, Greenville, SC, USA; Department of Medicine, Prisma Health, Greenville, SC, USA. Electronic address: alain.litwin@prismahealth.org.
² Department of Medicine, University of California San Francisco, San Francisco, CA, USA.
³ College of Pharmacy, University of Rhode Island, Providence, RI, USA; HIV and Viral Hepatitis Services, CODAC Behavioral Health, Providence, RI, USA.
⁴ Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
⁵ Department of Medicine, University of Washington, Seattle, WA, USA.
⁶ Department of Behavioral Medicine and Psychiatry, and Department of Medicine, Section of Infectious Diseases, West Virginia University School of Medicine, Morgantown, WV, USA.
⁷ Division of Infectious Diseases, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
⁸ Department of Medicine, Albert Einstein College of Medicine/Montefiore Medical Center, New York, NY, USA.
⁹ Department of Public Health Sciences, Clemson University, Clemson, SC, USA.
¹⁰ Department of Family and Social Medicine, Albert Einstein College of Medicine/Montefiore Medical Center, New York, NY, USA.
¹¹ Department of Family Medicine & Community Health, University of Massachusetts Chan Medical School, Worcester, MA, USA.
¹² Coalition for Global Hepatitis Elimination, The Task Force for Global Health, Decatur, GA, USA.
¹³ New York City Department of Health and Mental Hygiene, New York City, NY, USA.
¹⁴ Department of Psychology, Clemson University, Clemson, SC, USA; School of Health Research, Clemson University, Clemson, SC, USA.
¹⁵ College of Pharmacy, University of Rhode Island, Providence, RI, USA.
¹⁶ Office of Research Program Management, West Virginia University School of Medicine, Morgantown, WV, USA.
¹⁷ University of New Mexico Health Sciences Center, Department of Internal Medicine, University of New Mexico, Albuquerque, NM, USA.
¹⁸ Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
¹⁹ Department of Psychiatry and Behavioral Sciences, University of New Mexico, Albuquerque, NM, USA.
²⁰ Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

PMID: 36370741
DOI: 10.1016/S2468-1253(22)00275-8

Randomized Controlled Trial

Patient-centred models of hepatitis C treatment for people who inject drugs: a multicentre, pragmatic randomised trial

Alain H Litwin et al. Lancet Gastroenterol Hepatol. 2022 Dec.

. 2022 Dec;7(12):1112-1127.

doi: 10.1016/S2468-1253(22)00275-8.

Authors

Affiliations

¹ School of Health Research, Clemson University, Clemson, SC, USA; Department of Medicine, University of South Carolina School of Medicine, Greenville, SC, USA; Department of Medicine, Prisma Health, Greenville, SC, USA. Electronic address: alain.litwin@prismahealth.org.
² Department of Medicine, University of California San Francisco, San Francisco, CA, USA.
³ College of Pharmacy, University of Rhode Island, Providence, RI, USA; HIV and Viral Hepatitis Services, CODAC Behavioral Health, Providence, RI, USA.
⁴ Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
⁵ Department of Medicine, University of Washington, Seattle, WA, USA.
⁶ Department of Behavioral Medicine and Psychiatry, and Department of Medicine, Section of Infectious Diseases, West Virginia University School of Medicine, Morgantown, WV, USA.
⁷ Division of Infectious Diseases, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
⁸ Department of Medicine, Albert Einstein College of Medicine/Montefiore Medical Center, New York, NY, USA.
⁹ Department of Public Health Sciences, Clemson University, Clemson, SC, USA.
¹⁰ Department of Family and Social Medicine, Albert Einstein College of Medicine/Montefiore Medical Center, New York, NY, USA.
¹¹ Department of Family Medicine & Community Health, University of Massachusetts Chan Medical School, Worcester, MA, USA.
¹² Coalition for Global Hepatitis Elimination, The Task Force for Global Health, Decatur, GA, USA.
¹³ New York City Department of Health and Mental Hygiene, New York City, NY, USA.
¹⁴ Department of Psychology, Clemson University, Clemson, SC, USA; School of Health Research, Clemson University, Clemson, SC, USA.
¹⁵ College of Pharmacy, University of Rhode Island, Providence, RI, USA.
¹⁶ Office of Research Program Management, West Virginia University School of Medicine, Morgantown, WV, USA.
¹⁷ University of New Mexico Health Sciences Center, Department of Internal Medicine, University of New Mexico, Albuquerque, NM, USA.
¹⁸ Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
¹⁹ Department of Psychiatry and Behavioral Sciences, University of New Mexico, Albuquerque, NM, USA.
²⁰ Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

PMID: 36370741
DOI: 10.1016/S2468-1253(22)00275-8

Abstract

Background: To achieve WHO targets for the elimination of hepatitis C virus (HCV) as a public threat, an increased uptake of HCV treatment among people who inject drugs (PWID) is urgently needed. Optimal HCV co-located treatment models for PWID have not yet been identified. We aimed to compare two patient-centred models of HCV care in PWID with active drug use.

Methods: We did a pragmatic randomised controlled trial at eight US cities in eight opioid treatment programmes and 15 community health centres. PWID actively injecting within 90 days of study entry were randomly assigned (1:1) to either patient navigation or modified directly observed therapy (mDOT) using computer-generated variable block sizes of 2-6 stratified by city, clinical settings, and cirrhosis status. The randomisation code was concealed, in a centralised REDCap database platform, from all investigators and research staff except for an authorised data manager at the data coordinating centre. All participants received a fixed-dose combination tablet (sofosbuvir 400 mg plus velpatasvir 100 mg) orally once daily for 12 weeks. The primary outcome was sustained virological response (SVR; determined by chart review between 70 days and 365 days after end of treatment and if unavailable, by study blood draws), and secondary outcomes were treatment initiation, adherence (measured by electronic blister packs), and treatment completion. Analyses were conducted within the modified intention-to-treat (mITT; all who initiated treatment), intention-to-treat (all who were randomised), and per-protocol populations. This trial is registered with ClinicalTrials.gov, NCT02824640.

Findings: Between Sept 15, 2016, and Aug 14, 2018, 1891 individuals were screened and 1136 were excluded (213 declined to participate and 923 did not meet the eligibility criteria). We randomly assigned 755 participants to patient navigation (n=379) or mDOT (n=376). In the mITT sample of participants who were randomised and initiated treatment (n=623), 226 (74% [95% CI 69-79]) of 306 participants in the mDOT group and 236 (76% [69-79]) of 317 in the patient navigation group had an SVR, with no significant difference between the groups (adjusted odds ratio [AOR] 0·97 [95% CI 0·66-1·42]; p=0·35). In the ITT sample (n=755), 226 (60% [95% CI 55-65]) of 376 participants in the mDOT group and 236 (62% [57-67]) of 379 in the patient navigation group had an SVR (AOR 0·92 [0·68-1·25]; p=0·61) and in the per-protocol sample (n=501), 226 (91% [87-94]) of 248 participants in the mDOT group and 235 (93% [89-96]) of 253 in the patient navigation group had an SVR (AOR 0·79 [0·41-1·55]; p=0·44). 306 (81%) of 376 participants in the mDOT group and 317 (84%) of 379 participants in the patient navigation group initiated treatment (AOR 0·86 [0·58-1·26]; p=0·44) and, among those, 251 (82%) participants in the mDOT group and 264 (83%) participants in the patient navigation group completed treatment (AOR 0·90 [0·58-1·39]; p=0·63). Mean daily adherence was higher in the mDOT group (78% [95% CI 75-81]) versus the patient navigation group (73% [70-77]), with a difference of 4·7% ([1·9-7·4]; p=0·0010). 421 serious adverse events were reported (217 in the mDOT group and 204 in the patient navigation group), with the most common being hospital admission (176 in the mDOT group vs 161 in the patient navigation group).

Interpretation: In this trial of active PWID, both models resulted in high SVR. Although adherence was significantly higher in the mDOT group versus the patient navigation group, there was no significant difference in SVR between the groups. Increases in adherence and treatment completion were associated with an increased likelihood of SVR. These results suggest that active PWID can reach high SVRs in diverse settings with either mDOT or patient navigation support.

Funding: Patient-Centered Outcomes Research Institute, Gilead Sciences, Quest Diagnostics, Monogram Biosciences, and OraSure Technologies.

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Conflict of interest statement

Declaration of interests OF-N has served on advisory panels for Gilead Sciences and reports research funds from AbbVie paid to Johns Hopkins University. JF has received research grant support from Gilead Sciences. AYK has served on advisory boards for Biomarin. AFL received research grant support from Gilead and Merck. The Task Force for Global Health receives funds for the general support of the Coalition for Global Hepatitis Elimination from Abbott, Gilead, AbbVie, Merck, Siemens, Roche, Pharco, Zydus-Cadila, governmental agencies, and philanthropic organisations. AHL has served on advisory boards for Gilead Sciences and Merck Pharmaceuticals and received research funding from Gilead Sciences. SHM has received speaker fees from Gilead Sciences. LET has received UpToDate Royalties for peer review of viral hepatitis topics. All other authors declare no competing interests.

Comment in

Simplifying hepatitis C care models: a crucial step towards hepatitis C elimination.
Marshall AD, Matthews GV. Marshall AD, et al. Lancet Gastroenterol Hepatol. 2022 Dec;7(12):1066-1068. doi: 10.1016/S2468-1253(22)00306-5. Lancet Gastroenterol Hepatol. 2022. PMID: 36370732 No abstract available.

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Patient-centred models of hepatitis C treatment for people who inject drugs: a multicentre, pragmatic randomised trial

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Patient-centred models of hepatitis C treatment for people who inject drugs: a multicentre, pragmatic randomised trial

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