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Hepatitis C Reinfection in People Who Inject Drugs in Resource-Limited Countries: A Systematic Review and Analysis.

ABSTRACT: Hepatitis C (HCV) is a global pandemic. The World Health Organization has developed a strategic plan for HCV elimination that focuses on low- and middle-income countries (LMICs) and high-risk populations, including people who inject drugs (PWID). While direct-acting antiviral (DAA) therapies are highly effective at eliminating HCV infections and have few side effects, medical professionals and policymakers remain concerned about the risk of reinfection among PWID. This study is a systematic review of research measuring the rate of HCV reinfection among PWID in LMICs and identifies additional areas for further research. A systematic search strategy was used to identify studies documenting HCV reinfection after sustained virologic response in PWID in LMICs. We refined results to include studies where at least 50% of participants had DAA treatment for primary HCV infection. Pooled reinfection rate was calculated across all studies. Seven studies met eligibility criteria. Most studies were conducted in six upper middle-income countries (Mexico, Romania, Russia, Taiwan, Georgi, and Brazil) and one lower middle-income country (Bangladesh) with a total of 7665 participants. No study included information from PWID in low-income countries. Sample sizes ranged from 200 to 3004 individuals, with demographic data missing for most participants. Four studies used deep gene sequencing, and reflex genotyping procedures to differentiate reinfection (infection by a different HCV genotype/subtype) from virologic relapse (infection by the same strain). The follow-up time of people cured from primary chronic HCV infection ranged from 12 weeks to 6.6 years. The pooled reinfection rate of all seven studies was 2.8 (range: 0.02 to 10.5) cases per 100 person-years (PY). In the five studies that differentiated relapse from reinfection, the incidence of reinfection was 1.0 per 100 PY. To date, research on reinfection rates among PWID in LMICs remains limited. Research focused on PWID in low-income countries is particularly needed to inform clinical decision making and evidence-based programs. While rates of reinfection among PWID who complete DAA treatment in upper and lower middle-income countries were similar or lower than rates observed in PWID in high-income countries, the rates were highly variable and factors may influence the accuracy of these measurements. This systematic review identifies several areas for continued research. Policies concerning access to HCV testing and treatment should be comprehensive and not place restrictions on PWID in these settings.

SUBMITTER: Muller A

PROVIDER: S-EPMC7400365 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Hepatitis C Reinfection in People Who Inject Drugs in Resource-Limited Countries: A Systematic Review and Analysis.

Muller Abbe A Vlahov David D Akiyama Matthew J MJ Kurth Ann A

International journal of environmental research and public health 20200709 14

Hepatitis C (HCV) is a global pandemic. The World Health Organization has developed a strategic plan for HCV elimination that focuses on low- and middle-income countries (LMICs) and high-risk populations, including people who inject drugs (PWID). While direct-acting antiviral (DAA) therapies are highly effective at eliminating HCV infections and have few side effects, medical professionals and policymakers remain concerned about the risk of reinfection among PWID. This study is a systematic revi ...[more]

PMID: 32659974

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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.

Project description:Background & aimsScale-up of highly effective direct-acting antivirals (DAAs) for HCV among people who inject drugs (PWID) in Scotland has led to a reduction in the prevalence of viraemia in this population. However, the extent of reinfection among those treated with DAAs remains uncertain. We estimated HCV reinfection rates among PWID in Scotland by treatment setting, pre- and post-introduction of DAAs, and the potential number of undiagnosed reinfections resulting from incomplete follow-up testing.MethodsThrough linkage of national clinical and laboratory HCV data, a retrospective cohort of PWID who commenced treatment between 2000-2018 and achieved a sustained virological response (SVR) were followed up for reinfection to December 2019. Reinfection was defined as a positive HCV antigen or RNA test.ResultsOf 5,686 SVRs among 5,592 PWID, 4,126 (73%) had an HCV RNA or antigen test post-SVR. Of those retested, we identified 361 reinfections (3.9/100 person-years [PY]). The reinfection rate increased from 1.5/100 PY among PWID treated in 2000-2009 to 8.8/100 PY in 2017-2018. The highest reinfection rates were observed among those treated in prison (14.3/100 PY) and community settings (9.5/100 PY). Among those treated in the DAA era (2015-2018), 68% were tested within the first year post-SVR but only 30% in the second year; while 169 reinfections were diagnosed in follow-up, an estimated 200 reinfections (54% of the estimated total) had gone undetected.ConclusionsHCV reinfection rates among PWID in Scotland have risen alongside the scale-up of DAAs and broadened access to treatment for those at highest risk, through delivery in community drug services. Promotion of HCV testing post-SVR among PWID is essential to ensure those reinfected are identified and retreated promptly.Lay summaryIncreased rates of hepatitis C reinfection in Scotland were observed following the rapid scale-up of highly effective direct-acting antiviral (DAA) treatments among people who inject drugs. This demonstrates that community-based treatment pathways are reaching high-risk groups, regarded vital in efforts to eliminate the virus. However, we estimate that less than half of reinfections have been detected in the DAA era because of inadequate levels of retesting beyond the first year following successful treatment. Sustained efforts that involve high coverage of harm reduction measures and high uptake of annual testing are required to ensure prompt diagnosis and treatment of those reinfected if the goals of elimination are to be met.

Project description:Mounting evidence suggests that laws and policies prohibiting illegal drug use could have a central role in shaping health outcomes among people who inject drugs (PWID). To date, no systematic review has characterised the influence of laws and legal frameworks prohibiting drug use on HIV prevention and treatment.Consistent with PRISMA guidelines, we did a systematic review of peer-reviewed scientific evidence describing the association between criminalisation of drug use and HIV prevention and treatment-related outcomes among PWID. We searched MEDLINE, Embase, SCOPUS, PsycINFO, Sociological Abstracts, CINAHL, Web of Science, and other sources. To be included in our review, a study had to meet the following eligibility criteria: be published in a peer-reviewed journal or presented as a peer-reviewed abstract at a scientific conference; examine, through any study design, the association between an a-priori set of indicators related to the criminalisation of drugs and HIV prevention or treatment among PWID; provide sufficient details on the methods followed to allow critical assessment of quality; be published or presented between Jan 1, 2006, and Dec 31, 2014; and be published in the English language.We identified 106 eligible studies comprising 29 longitudinal, 49 cross-sectional, 22 qualitative, two mixed methods, four mathematical modelling studies, and no randomised controlled trials. 120 criminalisation indicators were identified (range 1-3 per study) and 150 HIV indicators were identified (1-5 per study). The most common criminalisation indicators were incarceration (n=38) and street-level policing (n=39), while the most frequent HIV prevention and treatment indicators were syringe sharing (n=35) and prevalence of HIV infection among PWID (n=28). Among the 106 studies included in this review, 85 (80%) suggested that drug criminalisation has a negative effect on HIV prevention and treatment, 10 (9%) suggested no association, five (5%) suggested a beneficial effect, one (1%) suggested both beneficial and negative effects, and five (5%) suggested both null and negative effects.These data confirm that criminalisation of drug use has a negative effect on HIV prevention and treatment. Our results provide an objective evidence base to support numerous international policy initiatives to reform legal and policy frameworks criminalising drug use.Canadian Institutes of Health Research and US National Institutes of Health.

Dataset Information

Hepatitis C Reinfection in People Who Inject Drugs in Resource-Limited Countries: A Systematic Review and Analysis.

Publications

Hepatitis C Reinfection in People Who Inject Drugs in Resource-Limited Countries: A Systematic Review and Analysis.

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