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Background & Aims HCV reinfection following successful treatment can compromise treatment outcomes. This systematic review assessed the rate of HCV reinfection following treatment among people with recent drug use and those receiving opioid agonist therapy (OAT). Methods We searched bibliographic databases and conference abstracts for studies assessing post-treatment HCV reinfection rates among people with recent drug use (injecting or non-injecting) or those receiving OAT. Meta-analysis was used to cumulate reinfection rates and meta-regression was used to explore heterogeneity across studies. Results Thirty-six studies were included (6,311 person-years of follow-up). The overall rate of HCV reinfection was 5.9/100 person-years (95% CI 4.1–8.5) among people with recent drug use (injecting or non-injecting), 6.2/100 person-years (95% CI 4.3–9.0) among people recently injecting drugs, and 3.8/100 person-years (95% CI 2.5–5.8) among those receiving OAT. Reinfection rates were comparable following interferon-based (5.4/100 person-years; 95% CI 3.1–9.5) and direct-acting antiviral (3.9/100 person-years; 95% CI 2.5–5.9) therapy. In stratified analysis, reinfection rates were 1.4/100 person-years (95% CI 0.8–2.6) among people receiving OAT with no recent drug use, 5.9/100 person-years (95% CI 4.0–8.6) among people receiving OAT with recent drug use, and 6.6/100 person-years (95% CI 3.4–12.7) among people with recent drug use not receiving OAT. In meta-regression analysis, longer follow-up was associated with lower reinfection rate (adjusted rate ratio [aRR] per year increase in mean/median follow-up 0.77; 95% CI 0.69–0.86). Compared with people receiving OAT with no recent drug use, those with recent drug use receiving OAT (aRR 3.50; 95% CI 1.62–7.53), and those with recent drug use not receiving OAT (aRR 3.96; 95% CI 1.82–8.59) had higher reinfection rates. Conclusion HCV reinfection risk following treatment was higher among people with recent drug use and lower among those receiving OAT. The lower rates of reinfection observed in studies with longer follow-up suggested higher reinfection risk early post-treatment. Lay summary Our findings demonstrate that although reinfection by hepatitis C virus occurs following successful treatment in people with recent drug use, the rate of hepatitis C reinfection is lower than the rates of primary infection reported in the literature for this population – reinfection should not be used as a reason to withhold therapy from people with ongoing injecting drug use. The rate of hepatitis C reinfection was lowest among people receiving opioid agonist therapy with no recent drug use. These data illustrate that harm reduction services are required to reduce the reinfection risk, while regular post-treatment hepatitis C assessment is required for early detection and retreatment.

[Marshall, A. D.; Cunningham, E. B.; Dore, G. J.; Grebely, J.] UNSW Sydney, Kirby Inst, Sydney, NSW, Australia. [Nielsen, S.] Freelance Epidemiologist, Madrid, Spain. [Aghemo, A.] Univ Milan, Fdn IRCCS CA Granda Osped Maggiore Policlin, Div Gastroenterol & Hepatol, Milan, Italy. [Alho, H.] Helsinki Univ Hosp, Abdominal Ctr, Helsinki, Finland. [Alho, H.] Univ Helsinki, Helsinki, Finland. [Backmund, M.] Univ Hosp Munich, Dept Med 2, Munich, Germany. [Bruggmann, P.] Arud Ctr Addict Med, Zurich, Switzerland. [Dalgard, O.] Univ Oslo, Akershus Univ Hosp, Dept Infect Dis, Oslo, Norway. [Dalgard, O.] Univ Oslo, Fac Med, Oslo, Norway. [Flisiak, R.] Med Univ Bialystok, Dept Infect Dis & Hepatol, Bialystok, Poland. [Foster, G.] Queen Mary Univ London, London, England. [Gheorghe, L.] Fundeni Clin Inst, Gastroenterol & Hepatol, Bucharest, Romania. [Goldberg, D.] Hlth Protect Scotland, Glasgow, Lanark, Scotland. [Goulis, I.] Dept Internal Med, Thessaloniki, Greece. [Hickman, M.] Univ Bristol, Social Med, Bristol, Avon, England. [Hoffmann, P.] Minist Hlth Luxembourg, Luxembourg, Luxembourg. [Jancoriene, L.] Vilnius Univ Hosp, Santariskiu Klin, Ctr Infect Dis, Vilnius, Lithuania. [Jarcuska, P.] Univ Hosp, Dept Internal Med 1, Kosice, Slovakia. [Jarcuska, P.] Univ Pavol Jozef Safarik, Kosice, Slovakia. [Kaberg, M.] Karolinska Univ Hosp, Dept Infect Dis, Stockholm, Sweden. [Makara, M.] St Istvan & St Laszlo Hosp, Hepatol Ctr, Budapest, Hungary. [Maimets, M.] Univ Tartu, Dept Internal Med, Tartu, Estonia. [Marinho, R.] Hosp Santa Maria, Med Sch Lisbon, Dept Gastroenterol & Hepatol, Lisbon, Portugal. [Maticic, M.] Univ Med Ctr, Clin Infect Dis & Febrile Illnesses, Ljubljana, Slovenia. [Norris, S.; Tait, M.] Dr Steevens Hosp, Natl Hepatitis Treatment Programme C, Hlth Serv Execut, Dublin, Ireland. [Olafsson, S.] Landspitali Univ Hosp, Dept Med, Div Gastroenterol, Reykjavik, Iceland. [Ovrehus, A.] Univ Southern Denmark, Odense Univ Hosp, Dept Infect Dis, Odense, Denmark. [Pawlotsky, J. -M.] Univ Paris Est, Hop Henri Mondor, Creteil, France. [Pocock, J.] Mater Hosp, Gastroenterol Dept, Msida, Malta. [Robaeys, G.] Ziekenhuis Oost Limburg, Dept Gastroenterol & Hepatol, Genk, Belgium. [Robaeys, G.] UHasselt, Dept Med & Life Sci, Hasselt, Belgium. [Robaeys, G.] UZLeuven, Dept Hepatol, Leuven, Belgium. [Roncero, C.] Univ Autonoma Barcelona, Hosp Univ Vall dHebron, Psychiat Serv, Addict & Dual Diag Unit, Barcelona, Spain. [Simonova, M.] Mil Med Acad, Dept Gastroenterol HPB Surg & Transplantol, Sofia, Bulgaria. [Sperl, J.] Inst Clin & Expt Med, Dept Hepatogastroenterol, Prague, Czech Republic. [Tolmane, I.] Infectol Ctr Latvia, Dept Hepatol, Riga, Latvia. [Tomaselli, S.] Off Publ Hlth, Vaduz, Liechtenstein. [van der Valk, M.] Acad Med Ctr, Dept Infect Dis, Amsterdam, Netherlands. [Vince, A.] Univ Zagreb, Sch Med, Univ Hosp Infect Dis, Zagreb, Croatia. [Lazarus, J. V.] Univ Copenhagen, Rigshosp, CHIP, Copenhagen, Denmark. [Lazarus, J. V.] Hosp Clin Barcelona, Barcelona Inst Global Hlth ISGlobal, Barcelona, Spain.

This study was funded by the Australian Government Department of Health and Ageing. The views expressed in this publication do not necessarily represent the position of the Australian Government. The Kirby Institute is affiliated with the Faculty of Medicine, University of New South Wales. The opinions expressed in this paper are those of the authors and do not necessarily represent that of Merck Sharp and Dohme. Support from Abbott Diagnostics for the supply of reagents is gratefully acknowledged. GD is supported by a National Health and Medical Research Council Practitioner Research Fellowships. JG is supported by a National Health and Medical Research Council Career Development Fellowship. BH is supported by a National Health and Medical Research Council Early Career Fellowship. The ARCHITECT HCV Ag kits for this study were kindly provided by Abbott.