A Phylogenetic Analysis of Hepatitis C Virus Transmission, Relapse, and Reinfection Among People Who Inject Drugs Receiving Opioid Agonist Therapy.
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ABSTRACT: Background
Understanding hepatitis C virus (HCV) transmission among people who inject drugs (PWID) is essential for HCV elimination. We aimed to differentiate reinfections from treatment failures and to identify transmission linkages and associated factors in a cohort of PWID receiving opioid agonist therapy (OAT).Methods
We analyzed baseline and follow-up specimens from 150 PWID from 3 OAT clinics in the Bronx, New York. Next-generation sequencing data from the hypervariable region 1 of HCV were analyzed using Global Hepatitis Outbreak and Surveillance Technology.Results
There were 3 transmission linkages between study participants. Sustained virologic response (SVR) was not achieved in 9 participants: 7 had follow-up specimens with similar sequences to baseline, and 2 died. In 4 additional participants, SVR was achieved but the participants were viremic at later follow-up: 2 were reinfected with different strains, 1 had a late treatment failure, and 1 was transiently viremic 17 months after treatment. All transmission linkages were from the same OAT clinic and involved spousal or common-law partnerships.Conclusion
This study highlights the use of next-generation sequencing as an important tool for identifying viral transmission and to help distinguish relapse and reinfection among PWID. Results reinforce the need for harm reduction interventions among couples and those who report ongoing risk factors after SVR.
SUBMITTER: Akiyama MJ
PROVIDER: S-EPMC7336560 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:UnlabelledHepatitis C virus reinfection and spontaneous clearance of reinfection were examined in a highly characterised cohort of 188 people who inject drugs over a five-year period. Nine confirmed reinfections and 17 possible reinfections were identified (confirmed reinfections were those genetically distinct from the previous infection and possible reinfections were used to define instances where genetic differences between infections could not be assessed due to lack of availability of hepatitis C virus sequence data). The incidence of confirmed reinfection was 28.8 per 100 person-years (PY), 95%CI: 15.0-55.4; the combined incidence of confirmed and possible reinfection was 24.6 per 100 PY (95%CI: 16.8-36.1). The hazard of hepatitis C reinfection was approximately double that of primary hepatitis C infection; it did not reach statistical significance in confirmed reinfections alone (hazard ratio [HR]: 2.45, 95%CI: 0.87-6.86, p=0.089), but did in confirmed and possible hepatitis C reinfections combined (HR: 1.93, 95%CI: 1.01-3.69, p=0.047) and after adjustment for the number of recent injecting partners and duration of injecting. In multivariable analysis, shorter duration of injection (HR: 0.91; 95%CI: 0.83-0.98; p=0.019) and multiple recent injecting partners (HR: 3.12; 95%CI: 1.08-9.00, p=0.035) were independent predictors of possible and confirmed reinfection. Time to spontaneous clearance was shorter in confirmed reinfection (HR: 5.34, 95%CI: 1.67-17.03, p=0.005) and confirmed and possible reinfection (HR: 3.10, 95%CI: 1.10-8.76, p-value=0.033) than primary infection. Nonetheless, 50% of confirmed reinfections and 41% of confirmed or possible reinfections did not spontaneously clear.ConclusionsHepatitis C reinfection and spontaneous clearance of hepatitis C reinfection were observed at high rates, suggesting partial acquired natural immunity to hepatitis C virus. Public health campaigns about the risks of hepatitis C reinfection are required.
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