Outcomes of Real-World Integrated HCV Microelimination for People Who Inject Drugs: An expansion of the Punjab Model

Abstract

Background: The prevalence of chronic hepatitis C (CHC) in People Who Inject Drugs (PWID) is 8-10% as compared to 3·6% in the general population in Punjab, India. We assessed the real-world efficacy and safety of free-of-charge generic direct-acting antivirals (DAAs), sofosbuvir with an NS5A inhibitor (ledipasvir, daclatasvir or velpatasvir)±ribavirin in the microelimination of CHC in PWID in a public health setting.

Methods: An integrated care team at 25 sites provided algorithm based DAAs treatment to PWID supervised by telemedicine clinics between 18th June 2016 and 31st July 2019. The primary endpoint was sustained virological response at 12 weeks (SVR-12); the secondary endpoints were treatment completion, adherence, safety, and adverse events. ClinicalTrials.gov number: NCT01110447.

Findings: We enrolled 3477 PWID (87·2% men; mean age 33·6±12·5 years; 83·8% rural; 6·8% compensated cirrhosis). While 2280 (65·5%) patients completed treatment, 1978 patients completed 12 weeks of follow up for SVR-12. SVR-12 was achieved in 91·1% of patients per protocol, 49.5% as per intention to treat (ITT) and 90·1% in a modified ITT analysis. Of 546 (15·7%) patients with treatment interruptions, 99 (19·7%) could be traced to test for SVR-12 with a cure rate of 77·8%. There were no major adverse events or consequent treatment discontinuation.

Interpretation: Integrated care of PWID with CHC with DAAs is safe and effective. Measures for reducing treatment interruptions will further improve outcomes.

Funding: The Government of the state of Punjab, India under the Mukh Mantri Punjab Hepatitis C Relief Fund (MMPHCRF) project, funds the project.

Keywords: ALT, alanine aminotransferase; CHC, chronic hepatitis C; CI, confidence interval; DAAs, direct-acting antiviral agents; DCV, Daclatasvir; DH, District Hospital; ECHO, Extension for Community healthcare Outcome; G, Genotype; HBV, hepatitis B virus; HCC, hepatocellular carcinoma; HCV; HCV, hepatitis C virus; IDU, injection drug use; INASL, Indian National Association for study of the Liver; India; LDV, ledipasvir; MMPHCRF, Mukh Mantri Punjab Hepatitis C Relief Fund; NVHCP, National Viral Hepatitis Control Programme; OST, opioid substitution therapy peg-interferon; PWID, People Who Inject Drugs; RBV, ribavirin; SOF, sofosbuvir; SVR, sustained virologic response; VEL, Velpatasvir; hepatitis C virus; injection drug use; microelimination; people who inject drugs.

Conflict of interest statement

None of the authors has any conflict of interest to declare.

© 2021 The Authors.

Figures

Figure 1

Patient enrolment and outcomes analysis. (a) per protocol (PP) analysis (Cure Rate = 91.0%) (b) Intention to treat (ITT) analysis where all interruptions were treated as failures (Cure Rate = 49.5%) and (c) a modified ITT analysis where all patients with successful sustained virological response (SVR-12) in the interruptions arm were included as cured. (Cure Rate= 91.1%) *Received at least 1-dose of treatment. ** Completed at least 4 weeks of treatment and 12 weeks of follow up.

Figure 2

Chronic Hepatitis C Elimination Strategy in India. The National Viral Hepatitis Control Programme was launched in 2018 to meet the 2030 target for viral hepatitis elimination in India using public health infrastructure with expansion of access to care, vaccination for hepatitis B, delivery of free-of-charge antiviral therapy for chronic hepatitis C and B, use of telemedicine tools to ensure specialist supervision, microelimination in subgroups like people who inject drugs (PWID), dialysis patients etc, improved biomedical waste disposal, blood banking safety, safety engineered syringes and collaboration with other health services. Abbreviations: DCV, daclatasvir; HCV, hepatitis C virus; PWID, people who inject drugs; NVHCP, National Viral Hepatitis Control Programme; RBV, ribavirin; SOF, sofosbuvir; VEL, velpatasvir.