The Impact of Medications for Opioid Use Disorder on Hepatitis C Incidence Among Incarcerated Persons: A Systematic Review

Abstract

Hepatitis C virus (HCV) is highly prevalent in the criminal justice system and in persons who inject drugs, particularly opioids. Data on the impact of medications for opioid use disorder (MOUD) are abundant for infectious and noninfectious outcomes but are limited for justice-involved settings. This systematic review and meta-analysis focuses on the impact of MOUD on HCV incidence for persons in prisons and jails. Six studies were included in the qualitative synthesis, of which 4 were included for meta-analysis. A varied MOUD effect on HCV incidence was observed in part due to wide variability in prison and jail risk environments.

Introduction

There are an estimated 71 million persons globally living with hepatitis C virus (HCV) infection.¹ A significant burden of this disease is in people who inject drugs (PWID) such as opioids, and the global prevalence among PWID is estimated at approximately 40%.² In particular, the recent opioid epidemic has been associated with a spike in incident HCV cases among young PWID.³ Due in part by widespread criminalization of drug use, persons who use drugs are disproportionately represented worldwide in the criminal justice system (CJS).

The confluence of incarceration, HCV and opioid use requires evidence-based management that can address these complex and interdisciplinary public health concerns. The data on HCV transmission in the CJS, however, are limited. A systematic review evaluating HCV incidence in prisons and other closed settings meta-analyzed data from 4 sources and demonstrated a general incidence of 1.4 per 100 person-years and 16.4 per 100 person-years in detainees with a history of injection drug use (IDU).⁴ Even less, however, is known about strategies to mitigate HCV transmission in this setting and their effectiveness, particularly the impact of medications for treatment of opioid use disorder (OUD) (MOUD e.g. methadone, buprenorphine, extended-release naltrexone). MOUD have been associated with a multitude of health related outcomes including reduction in opioid use, overdose death, HIV transmission, maintenance of sustained viral response (SVR) in persons with treated HCV infection, and improved HIV viral suppression in persons living with HIV (PLH).^5–11 Notably, the benefit of MOUD also includes a reduction in acquisition of HCV in the community.¹² Despite the significant evidence base, incorporation of MOUD into the global CJS has faced resistance due to stigma and cost, precluding widespread limitation. We undertook a systematic review with the aim of assessing the effect of MOUD on HCV incidence in prisons and jails worldwide.

Methods

The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statements for reporting systematic reviews were used for this study.¹³ The study protocol was registered with PROSPERO prior to title and abstract review (CRD# 42019131996).

Study Selection

A systematic search of the literature was conducted in conjunction with a medical librarian in the databases Cochrane Library, Ovid Medline, Ovid Embase, PubMed, Scopus, Google Scholar, and Web of Science Core Collection to find articles published from the inception of each database until the final search on December 2019. The preliminary searches were performed in all of the databases on June 10, 2019 after being peer-reviewed by a second medical librarian, and the search was repeated December 10, 2019. The search was not limited by publication type, language or date. Databases were searched using a combination of controlled and free text terms (Tables 1–6; see also search strategy in Table 2).

Citations from all databases were imported into an Endnote X9 library. Duplicates were removed in Endnote, reducing the initial list of 3,587 citations to 1,939 citations. The corpus of 1,929 abstracts were imported into Covidence, a screening and data extraction tool. Two independent screeners (N.S, A.W) performed a title and abstract review with a third screener available if needed to resolve ties. The screeners selected a total of 74 records for full text review. All full manuscripts were assessed and adjudicated for relevance by two independent authors (N.S, A.W) with no resulting discrepancies. Non-English full manuscripts were read using Google Translate or, if needed, a colleague with native language proficiency.

Studies were included if: 1) They took place in a setting of active incarceration (prison or jail); 2) There was report of MOUD received by detainees (methadone, buprenorphine, or extended-release naltrexone); 3) there was data on either incident HCV infection or reinfection. Incidence data was to be evaluated and reported in person-year format. We included studies that measured incidence by seroconversion, new viremia, or cross-sectional analysis with antibody negative PCR positive participants as has been previously described.¹⁴ Studies that took place in alternate settings such as community supervision (parole), detention, or non-criminal justice locations were excluded. Reviews, editorials, and commentary were also excluded. Authors were contacted if there was any missing data such as incidence data as analyzed by MOUD receipt, or for unpublished data on continually incarcerated subsets of persons. Some publications were evaluations of the same cohort over time – the most recent and inclusive sampling was identified and included in the analysis.

Data Extraction and Analysis

Data from the included studies were extracted by NS and checked for accuracy by AW (see Table 7). We extracted crude hazard ratios (HRs) from longitudinal studies that measured incident HCV infection with and without MOUD. Cross sectional studies were not included together with longitudinal studies in the aggregated quantitative analysis.

Risk of bias was assessed for the outcome of interest in each included study using the Newcastle-Ottawa scale¹⁵ for nonrandomized studies and the Cochrane risk of bias¹⁶ for randomized controlled trials. The variables assessed for in comparison of cohorts were: percentage of injection drug use, non-opioid substance use, availability of syringe service programs (SSPs), and percentage uptake of MOUD.

The effect of MOUD on HCV incidence was expressed as adjusted hazard ratios. For studies that did not report hazard ratios we used the incidence rate ratio and calculated 95% confidence intervals. Hazard rates were pooled using random effects meta-analysis as described by DerSimonian and Laird.¹⁷ Between-study heterogeneity was estimated using the I² statistic. I² values of 25%, 50% and 75% were considered low, moderate and high heterogeneity.¹⁸ Because the number of included studies was less than ten, we did not perform meta-regression or test for publication bias using a funnel plot. Statistical analysis was performed using Stata/IC, version 16.1 (StataCorp, College Station, Texas).

Results

The initial and follow-up search combined returned 3,857 citations in total as shown in Figure 1. After removal of duplicates, 1939 citations remained. Initial title and abstract screening removed 1,865 articles and 74 manuscripts remained for full evaluation. Sixty-eight manuscripts were excluded, for reasons listed in Figure 1. Authors were contacted for unpublished data to determine eligibility in 16 instances. Ultimately 6 studies were included for final qualitative analysis, of which 4 were suitable for meta-analysis. Detailed study assessments and variables are reported in Table 7.

Figure 1:

PRISMA Flowchart.

A total of 6 studies were included that contained data on HCV incidence reported in relation to MOUD.^19–24 Four of the studies were longitudinal analyses (3 observational, 1 randomized controlled trial (RCT)) and two were cross-sectional analyses. Two of the cohorts were based out of Australia, 2 from Spain, 1 from Denmark and 1 from Scotland. One study described a cohort of patients who had previously been treated for HCV and retrospectively evaluated for reinfection.²¹

HCV Incidence

HCV incidence in each cohort, shown in Table 7, varied based on geographic location and incarcerated setting. HCV incidence for sub cohorts without MOUD ranged from 6.61²⁰ (Spain, 1990s) to 31.7 per 100 person-years²² (Australia, 1998). HCV incidence for subcohorts with MOUD ranged from 1.35²⁰ (Spain, 1990s) to 24.3 per 100 person-years²² (Australia, 1998).

All studies contained populations of incarcerated persons who were at risk of HCV acquisition and had excluded those with preexisting HCV infection. Four of the studies^19,22–24 described populations that were solely under continuous incarceration for the given analyses. The two Spanish cohorts^20,21 included persons who were in prison that were both continuously incarcerated and those that had been released with possible reincarceration. Author contact was pursued for subanalysis of HCV incidence related to MOUD in these continuously incarcerated populations but the data were unavailable.

Meta-Analysis

Of the six studies identified, 4 were suitable for meta-analysis^19–22 and summary incidence calculation as shown in Table 7. Prior to aggregation, HCV incidence was found to be non-significantly reduced in the MOUD population for 3 of the studies^20–22 and non-significantly increased in the MOUD population in the other.¹⁹ When the effect of MOUD on HCV acquisition was analyzed as a hazard ratio, the pooled risk was 0.91 (0.47 to 1.77; p= 0.505, I²= 0) as summarized in Figure 2. The cross-sectional evaluations had overall low event rates for HCV acquisition precluding accurate estimation of MOUD effect.

Figure 2:

Pooled Adjusted Hazard Ratio of MOUD Effect on HCV Incidence.

Substance Use and Risk Characteristics

There was a wide variability in the underlying substance use demographics of each cohort as shown in Table 8. Dolan et al.²² had specific inclusion criteria for male prisoners with heroin use seeking methadone maintenance therapy (i.e. consistent with OUD per DSM-5) and there was > 80% heroin use at baseline along with 40% methamphetamine use. Despite the entire cohort being actively incarcerated, continued injecting occurred during the 4-month follow-up evaluation in 75% of controls and 34% of the treatment arm. The other Australian study by Cunningham et al.¹⁹ was a prospective observational cohort that enrolled in two discrete time periods from roughly 2005 to 2014. In the first group of enrollment, together with being HCV seronegative, all of the participants had a lifetime history of IDU. In the second group of enrollment, participants had either a lifetime history of IDU or another potential HCV risk factor (i.e. history of tattooing, piercing, or blood fights). An overall total of 33% of individuals reported ongoing IDU since entering prison, together with 18% stimulant injection and methadone/buprenorphine injection.

The remaining 4 studies^20,21,23,24 did not specifically recruit persons with substance use but did report data on substance using sub-populations. One Spanish cohort²⁰ evaluated HCV seroconversion in a single prison in Barcelona over a decade with specific subgroup analyses in persons with IDU on methadone maintenance therapy (MMT) and IDU without MMT. The overall population with IDU, though, was low, at 7%. The other Spanish cohort²¹ evaluated HCV reinfection after treatment with pre direct acting antiviral (DAA) based regimens and the lifetime IDU prevalence was 81%, though the percentage of active IDU during the study evaluation period was reported as 10.1%. Both cross-sectional studies^23,24 evaluated general inmate populations from multiple prisons and jails. In the study by Soholm et al.²⁴, 8.5% of the population reported IDU and 3.6% reported injecting drugs in prison. The Scottish cohort by Taylor et al.²³ reported a 32% lifetime history of IDU, but in-prison injecting was described as “low” in frequency.

MOUD and Harm Reduction Characteristics

Similarly, there was wide variability in the degree of MOUD uptake in substance using populations and availability of adjunctive harm reduction services. Cunningham et al.¹⁹ reported an uptake of MMT or buprenorphine in about 15 to 20% of their originally recruited cohort with a lifetime IDU history. There were no syringe service programs in this study but bleach disinfectant materials were available. Methadone allocation was randomized in Dolan et al²², but there was crossover reported in both study arms; 68% of the treatment group were still on MMT at 4 months, and 19% of the control subjects started MMT during the trial period. The average methadone dose was 61 mg for this study. No syringe service resources were available however. In both Spanish cohorts^20,21, MMT was offered to all persons with IDU, and SSPs were more widely available. In Marco et al 2013²¹, 40% of those with IDU were on MMT throughout the study evaluation, and 3 out of 4 of the participating prisons had SSPs. Both cross-sectional cohorts^23,24 had moderate proportions of MOUD uptake with Taylor et al.²³ reporting that 57% of PWID were on MOUD at the time of interview, and Soholm et. al²⁴ reporting that 47% of the PWID were on MOUD. Neither prison system in these cohorts, however, reported using SSPs.

HCV Reinfection

Only one study was identified that reported HCV reinfection related to MOUD²¹. For persons within prison with IDU reported and MOUD receipt, the HCV incidence rate was 1.64 per 100 person-years, compared to 7.49 per 100 person-years in persons within prison with a history IDU and no MOUD. Notably, though continuously incarcerated persons were included, the study was not limited to this population and included those that had been released with possible reincarceration.

Discussion

The transmission of HCV virus in prisons and jails is intricately related to the carceral management of substance use disorders (SUDs) that involve injection drug use (IDU), in particular opioids. To our knowledge, our systematic review is the first to address the effect of medication treatment for OUD on HCV acquisition in the justice-involved setting.

Our study reveals a high degree of variability for the effect of MOUD on HCV incidence and reinfection. Despite two studies in the quantitative analysis suggesting a reduced HCV incidence in PWID on MOUD, the fourth study and largest cohort¹⁹ suggested a correlation between MOUD receipt and elevated HCV incidence. As has been previously reported by the author group^25–27, the reasons for this finding in the fourth study, known as the HITS cohort, are likely multifactorial. First, the overall MOUD uptake in their study population was relatively low. In the first half of the study, only 15 to 20% of the populations were retained on MMT or buprenorphine, all of whom had a lifetime history of IDU. Second, the HITS cohort was observational and nonrandomized, and hence those prescribed methadone or buprenorphine might represent a subpopulation of those with more severe OUD leading to more risky addiction behaviors. This was corroborated by a high degree of in prison injecting, including approximately 18% with stimulant injection, and even injection of buprenorphine and methadone.

The range of MOUD effect on HCV incidence likely reflects the analogous range of unique risk environments that each incarcerated setting represents. In Dolan et al²², the single RCT included in this meta-analysis, there was accordingly the least bias in MOUD allocation by virtue of randomization. HCV incidence was high, similar to the HITS cohort¹⁹, and a nonsignificant trend towards reduction of HCV incidence in those with methadone was reported. Both of these Australian cohorts likely represent similar risk environments with high rates of co-stimulant use and in-prison injecting. Notably, both cohorts had no SSPs. In comparison, the two cohorts by Marco et al^20,21 had relatively lower burdens of PWID, and yet SSPs were available to the participants in the majority of the prisons and jails. Although our analysis was limited in power by the number of relevant included manuscripts, further study of the MOUD effect in the presence or absence of SSPs or in terms of high versus low MOUD uptake would be informative. Whether MOUD type affects prison HCV transmission rates is also as of yet unclear. When the burden of high risk injecting and sharing of works is substantial, implementation of factors such as high MOUD uptake and SSPs likely become more integral to reducing HCV transmission, as has been shown in non-incarcerated populations.²⁸ Provision of SSPs likely becomes all the more important when stimulant use is highly prevalent and MOUD is hence not effective.

For the cross-sectional studies that were not included in the quantitative analysis^23,24, both had low overall incidences of HCV infection and limited event rates in the continuously incarcerated populations preventing assessment of MOUD effect. However, the authors of these studies suggested that relatively low in prison injecting populations, coupled with high uptake of MOUD (47 to 57%) resulted in an overall low HCV incidence.

Relevant manuscripts regarding the MOUD effect on HCV reinfection post treatment in the CJS were the most limited and had the highest element of bias. In Marco et al 2013²¹, the only included reinfection study, participants who had been treated with interferon based regimens were surveilled with HCV RNA PCR from 2003–2010 on an annual basis. The overall reinfection rate was relatively low at 5.27 per 100 person-years though this was confounded by the many persons who were released from prison during the study period. For those with IDU and on an effective dose of methadone, the incidence was 1.64 per 100 person-years compared to 7.49 per 100 person-years in those with IDU not on an effective methadone dose. Though this incidence rate difference itself was nonsignificant, the authors found a significant difference when analyzed as a proportion (2.1% on MMT versus 16.3% not on MMT; p = 0.031). These data are similar to the extension arm of the PREVAIL study¹⁰ that observed HCV reinfection rates as low as 1.22 per 100 person-years in a population that was fully comprised of persons with OUD on agonist therapy. More data is needed to corroborate the incidence of HCV reinfection in the CJS to support feasibility of successful treatment and more widespread initiation of DAAs in prisons and jails.

Novel public health strategies are shaping the landscape of future carceral HCV management and are areas for future study on the associated impact of MOUD. Treatment as prevention and elimination of HCV from prison “micro-environments” has been successfully demonstrated, notably in one study in the context of 33% MOUD coverage for PWID and 18% of the population utilizing SSPs.²⁹ HCV modeling of U.S. prisons has shown that nationwide opt-out screening and treatment would result in a significant reduction of new infections including in the community, but have been limited in their accounting for the role of MOUD and harm reduction services.³⁰

Limitations

Our study was limited by the scarcity of published literature on HCV incidence in incarcerated settings, particularly as it relates to its modulation by MOUD. A proportion of the full manuscripts that were reviewed had HCV incidence data but no collection of data on OUD treatment on an individual participant level.

Efforts were made to restrict inclusion to studies that only recorded HCV incidence in continuously incarcerated persons or reported data for the continuously incarcerated population separately. Recent data has shown that the risk period after release, particularly in the acute period immediately after release, represents a different and higher risk time period in which HCV acquisition is about 60% higher than other non-justice involved time periods.³¹ Even after contacting authors for clarification, separate incidence data for continuously incarcerated persons were unable to be obtained for two of the studies included. Ultimately, though, this bias likely overestimates rather than underestimates of HCV incidence reported both with and without MOUD, and perhaps underestimates the MOUD treatment effect. Other mechanisms for HCV transmission, such as tattooing, anal sex, or fights with transmission of blood, would not be mitigated by MOUD therapy and could also reduce the impact of any potential treatment effect.

Summary

While this systematic review revealed a heterogenous effect of MOUD on in-prison HCV incidence, it more likely represents the varied risk environments that each incarcerated setting represents, and that additional interventions such as syringe service programs are needed for incarcerated environments. Modulation of HCV acquisition is but one putative benefit of MOUD, which is a crucial evidence based therapy that should be offered to all persons with OUD regardless of setting. The multitude of health related outcomes, both infectious and non-infectious, are undeniable for those with opioid use disorder. There have been slow gains in the expansion of access to MOUD in incarcerated settings.^32,33 Similarly, strategies such as treatment as prevention and micro elimination of HCV with direct-acting antiviral therapy are gaining recognition. Future study will be needed to best understand how to maximally care for and mitigate the risk of persons with opioid use disorder in the criminal justice system as it relates to HCV and their overall health.

Key Points:

• HCV is highly prevalent in those with opioid use disorders (OUD) and in justice-involved populations.

• The data on the effect of medication treatments for OUD (MOUD e.g. methadone, buprenorphine, extended-release naltrexone) on HCV incidence in prisons and jails is limited.

• MOUD effect on HCV incidence in prisons and jails was mixed in part due to the variability in each individual risk environment, suggesting the need for additional harm reduction such as syringe service programs.

Appendix

Table 1.

PRISMA Checklist

	#	Checklist item	Reported on page #
TITLE
Title	1	Identify the report as a systematic review, meta-analysis, or both.	1
ABSTRACT
Structured summary	2	Provide a structured summary including, as applicable: background; objectives; data sources; study eligibility criteria, participants, and interventions; study appraisal and synthesis methods; results; limitations; conclusions and implications of key findings; systematic review registration number.	3
INTRODUCTION
Rationale	3	Describe the rationale for the review in the context of what is already known.	3
Objectives	4	Provide an explicit statement of questions being addressed with reference to participants, interventions, comparisons, outcomes, and study design (PICOS).	4
METHODS
Protocol and registration	5	Indicate if a review protocol exists, if and where it can be accessed (e.g., Web address), and, if available, provide registration information including registration number.	5
Eligibility criteria	6	Specify study characteristics (e.g., PICOS, length of follow-up) and report characteristics (e.g., years considered, language, publication status) used as criteria for eligibility, giving rationale.	6
Information sources	7	Describe all information sources (e.g., databases with dates of coverage, contact with study authors to identify additional studies) in the search and date last searched.	5–6
Search	8	Present full electronic search strategy for at least one database, including any limits used, such that it could be repeated.	Appendix
Study selection	9	State the process for selecting studies (i.e., screening, eligibility, included in systematic review, and, if applicable, included in the meta-analysis).	4–6
Data collection process	10	Describe method of data extraction from reports (e.g., piloted forms, independently, in duplicate) and any processes for obtaining and confirming data from investigators.	4–6
Data items	11	List and define all variables for which data were sought (e.g., PICOS, funding sources) and any assumptions and simplifications made.	5–6
Risk of bias in individual studies	12	Describe methods used for assessing risk of bias of individual studies (including specification of whether this was done at the study or outcome level), and how this information is to be used in any data synthesis.	7
Summary measures	13	State the principal summary measures (e.g., risk ratio, difference in means).	6–7
Synthesis of results	14	Describe the methods of handling data and combining results of studies, if done, including measures of consistency (e.g., I2) for each meta-analysis.	7
Section/topic	#	Checklist item	Reported on page #
Risk of bias across studies	15	Specify any assessment of risk of bias that may affect the cumulative evidence (e.g., publication bias, selective reporting within studies).	15; Appendix
Additional analyses	16	Describe methods of additional analyses (e.g., sensitivity or subgroup analyses, meta-regression), if done, indicating which were pre-specified.	7
RESULTS
Study selection	17	Give numbers of studies screened, assessed for eligibility, and included in the review, with reasons for exclusions at each stage, ideally with a flow diagram.	6
Study characteristics	18	For each study, present characteristics for which data were extracted (e.g., study size, PICOS, follow-up period) and provide the citations.	Table 1
Risk of bias within studies	19	Present data on risk of bias of each study and, if available, any outcome level assessment (see item 12).	6–7
Results of individual studies	20	For all outcomes considered (benefits or harms), present, for each study: (a) simple summary data for each intervention group (b) effect estimates and confidence intervals, ideally with a forest plot.	6–9
Synthesis of results	21	Present results of each meta-analysis done, including confidence intervals and measures of consistency.	6–9
Risk of bias across studies	22	Present results of any assessment of risk of bias across studies (see Item 15).	6; Appendix
Additional analysis	23	Give results of additional analyses, if done (e.g., sensitivity or subgroup analyses, meta-regression [see Item 16]).	6–9
DISCUSSION
Summary of evidence	24	Summarize the main findings including the strength of evidence for each main outcome; consider their relevance to key groups (e.g., healthcare providers, users, and policy makers).	9–11
Limitations	25	Discuss limitations at study and outcome level (e.g., risk of bias), and at review-level (e.g., incomplete retrieval of identified research, reporting bias).	11–15
Conclusions	26	Provide a general interpretation of the results in the context of other evidence, and implications for future research.	11–15
FUNDING
Funding	27	Describe sources of funding for the systematic review and other support (e.g., supply of data); role of funders for the systematic review.	1

From Moher D, Liberati A, Tetzlaff J, Altman DG, The PRISMA Group (2009). Preferred Reporting Items for Systematic Reviews and Meta-Analyses: The PRISMA Statement. PLoS Med 6(7): e1000097. doi:10.1371/journal.pmed1000097; with permission. For more information, visit: www.prisma-statement.org.

Table 2.

Search Strategy

Below is the search strategy for Ovid MEDLINE to identify potentially relevant studies. MeSH headings are in bold. Additional search strategies available upon request (alyssa.grimshaw@yale.edu).

prisons/ or prisoners/ or criminals/ (incarcerat* or criminal justice or prison* or jail* or court* or correctional or inmate* or convict* or offender* or criminal* or penal institution* or detained or detainee or imprison* or behind bars or confinement or confined or penitentiar* or detention* or justice involve*).mp. 1 or 2 exp Narcotics/ or exp Opioid-Related Disorders/ or exp Morphine Derivatives/ (opioid* or opiate* or heroin or Diacetylmorphine or diamorphine).mp. OUD.ti,ab. (narcotic adj3 (depend* or abuse* or addict*)).mp. Substance Abuse, Intravenous/ (“injection drug use” or “intravenous drug use” or “people who inject drugs”).mp. (IDU or IVDU or PWID).ti,ab. exp Methadone/ or exp Buprenorphine/ or Naltrexone/ (methadone or buprenorphine or naltrexone).mp. or/4–12 3 and 13 exp Hepatitis C/ (hepatitis C or hep c or PT-NANBH).mp. “Parenterally-Transmitted Non-A, Non-B Hepatitis”.mp. (HCV or CHC).ti,ab. 15 or 16 or 17 or 18 14 and 19

Table 3:

List of Excluded Manuscripts

Year	First Author	Title	Journal	Exclusion Reason
2014	Andres	Efficacy of treatment with pegylated interferon alfa-2a plus ribavirin in prison inmates with or without personality disorder. Subanalysis of the perseo study	Journal of Hepatology	No Reinfection Data
2004	Anonymous	Canada: study provides further evidence of risk of hepatitis C and HIV transmission in prisons	HIV/AIDS Policy & Law Review / Canadian HIV/AIDS Legal Network	NO HCV Incidence Data
2009	Arora	Project ECHO (extension for community healthcare outcomes): Knowledge networks expand access to Hepatitis C (HCV) treatment with pegylated interferon and ribavirin in rural areas and prisons. Care is as effective as a university HCV clinic	Hepatology	No Reinfection Data
2001	Arrada	[Prevalence of HBV and HCV infections and incidence of HCV infection after 3, 6 and 12 months detention in La Sante prison, Paris]	Annales de Medecine Interne	No MOUD Data
2013	Asl	Outcome assessment of a triangular clinic as a harm reduction intervention in Rajaee-Shahr Prison, Iran	Harm Reduction Journal	No HCV Incidence Data
2010	Bate	High prevalence of late relapse and reinfection in prisoners treated for chronic hepatitis C	Journal of Gastroenterology & Hepatology	Wrong Outcomes
2013	Boelen	Molecular epidemiology and social network analysis to track HCV transmission in high-risk communities: Injecting drug users in prisons of New South Wales, Australia	Journal of Hepatology	Wrong Outcomes
2010	Boonwaat	Establishment of a successful assessment and treatment service for Australian prison inmates with chronic hepatitis C	Medical Journal of Australia	No Reinfection Data
2008	Brant	Diagnosis of acute hepatitis C virus infection and estimated incidence in low- and high-risk English populations	Journal of Viral Hepatitis	No MOUD Data
2015	Bretana	Transmission of Hepatitis C Virus among Prisoners, Australia, 2005–2012	Emerging Infectious Diseases	Duplicate Study
2004	Butler	Prisoners are at risk for hepatitis C transmission	European Journal of Epidemiology	No MOUD Data
2012	Cameron	NK cell activity in exposed-uninfected prison inmates may protect against Hepatitis C infection	Journal of Hepatology	Wrong Outcomes
2004	Champion	Incidence of hepatitis C virus infection and associated risk factors among Scottish prison inmates: a cohort study	American Journal of Epidemiology	No MOUD Data
2016	Chen	The excellent outcome of interferon-based hepatitis C treatment in Taiwanese incarcerated patients	Hepatology International	No Reinfection Data
2008	Chong	Screening blood-borne virus among incarcerated inmates	International Journal of STD & AIDS	Wrong Outcomes
2000	Christensen	Prevalence and incidence of bloodborne viral infections among Danish prisoners	European Journal of Epidemiology	No MOUD Data
2017	Corless	Managing hepatitis C virus infection in prisonsame disease, different barriers	Gut	No Reinfection Data
1995	Crofts	Spread of bloodborne viruses among Australian prison entrants	BMJ	No MOUD Data
1996	Crofts	Risk behaviours for blood-borne viruses in a Victorian prison	Australian and New Zealand Journal of Criminology	NO HCV Incidence Data
2018	Cunningham	Ongoing incident hepatitis c virus infection among people with a history of injecting drug use in an Australian prison setting	Journal of the Canadian Association of Gastroenterology	Duplicate Study
2018	Cunningham	Longitudinal injecting risk behaviours among people with a history of injecting drug use in an Australian prison setting: The HITS-p study	International Journal of Drug Policy	Wrong Outcomes
2017	Cunningham	Ongoing incident hepatitis C virus infection among people with a history of injecting drug use in an Australian prison setting, 2005–2014: The HITS-p study	Journal of Viral Hepatitis	Duplicate Study
2016	Cunningham	Stable incidence of hepatitis C virus infection among people with a history of injecting drug use in an Australian prison setting, 2005–2014: The HITS-p study	Journal of Hepatology	Duplicate Study
2005	Dolan	Four-year follow-up of imprisoned male heroin users and methadone treatment: mortality, reincarceration and hepatitis C infection	Addiction	Wrong Outcomes
2010	Dolan	Incidence and risk for acute hepatitis C infection during imprisonment in Australia	European Journal of Epidemiology	Duplicate Study
2018	Farley	Ten-year durability of sustained viral response after hepatitis C treatment in Canadian correctional institutions	Hepatology	No Reinfection Data
2009	Farley	The effects of treatment for hepatitis c virus infection in methadone maintenance and non methadone maintenance	Canadian Journal of Gastroenterology. Conference: Canadian Digestive Diseases Week	No Reinfection Data
2011	Farley	Methadone, IDU relapse and HCV re-infection after HCV therapy in Canadian community and inmate populations	Journal of Hepatology	No HCV Incidence Data
2012	Farley	Re-infection of hepatitis C virus infection in HIV/HCV co-infected inmates of correctional institutions, Canada	Journal of the International AIDS Society	Duplicate Study
2011	Farley	Successful HCV treatment in correctional facilities in British Columbia, Canada: 10 years experience	Hepatology	No Reinfection Data
2013	Farley	Treatment response among HCV genotype 1 and their subtypes	Hepatology International	Wrong Outcomes
2005	Farley	Feasibility and outcome of HCV treatment in a Canadian federal prison population	American Journal of Public Health	No Reinfection Data
2016	Fernandez-Gonzalez	Sofosbuvir/ledipasvir in Spanish prison population with chronic hepatitis C	Journal of Hepatology	No Reinfection Data
2000	Ford	HIV, hepatitis C and risk behaviour in a Canadian medium-security federal penitentiary. Queen’s University HIV Prison Study Group	QJM	No HCV Incidence Data
2007	Haber	Correlates of incident HCV infection and seronegative-immune status in high risk, IDU prisoners	Hepatology	Duplicate Study
1999	Haber	Transmission of hepatitis C within Australian prisons	Medical Journal of Australia	No HCV Incidence Data
2017	Hajarizadeh	Incidence of hepatitis C virus infection in two maximum-security prisons in New South Wales, Australia: The SToP-C study	Journal of Hepatology	No MOUD Data
2001	Heinemann	Prevention of bloodborne virus infections among drug users in an open prison by syringe vending machines. [German]	Sucht	No MOUD Data
2010	Hernandez-Fernandez	[Results of the Spanish experience: a comprehensive approach to HIV and HCV in prisons]	Revista Espanola de Sanidad Penitenciaria	No HCV Incidence Data
1992	Lanciani	Viral infections in a sample of intravenous drug abuser prisoners	Panminerva Medica	No HCV Incidence Data
2018	Lin	Treatment of Non-cirrhotic Incarcerated Genotype 6 Chronic Hepatitis C Injection Drug Users, Compared with Genotype 1	Journal of Internal Medicine of Taiwan	No Reinfection Data
2008	Lloyd	Predictors of HCV incidence in IDU prison inmates	Journal of Gastroenterology and Hepatology	Duplicate Study
2014	Luciani	A prospective study of hepatitis C incidence in Australian prisoners	Addiction	Duplicate Study
2004	Macalino	Prevalence and incidence of HIV, hepatitis B virus, and hepatitis C virus infections among males in Rhode Island prisons	American Journal of Public Health	No MOUD Data
2010	Marco Mourino	[Predictors of adherence to treatment of chronic hepatitis C in drug-dependent inmate patients in four prisons in Barcelona, Spain]	Revista Espanola de Salud Publica	No Reinfection Data
2010	Marco Mourino	[Predictors of adherence to treatment of chronic hepatitis C in drug-dependent inmate patients in four prisons in Barcelona, Spain]. [Spanish]	Revista Espanola de Salud Publica	No Reinfection Data
2018	Marco	Reinfection in inmates with sustained viral response after treatment for chronic Hepatitis C from 2002 through 2016 in Catalonia (Spain)	Hepatology	Duplicate Study
2019	Marco	Reinfection in a large cohort of prison inmates with sustained virological response after treatment of chronic hepatitis C in Catalonia (Spain), 2002–2016	International Journal of Drug Policy	No MOUD Data
2008	Maru	Clinical outcomes of hepatitis C treatment in a prison setting: feasibility and effectiveness for challenging treatment populations	Clinical Infectious Diseases	No Reinfection Data
2009	Miller	Hepatitis C virus infection in South Australian prisoners: seroprevalence, seroconversion, and risk factors	International Journal of Infectious Diseases	No MOUD Data
2015	Nelwan	Effect of Hiv Prevention and Treatment Program on Hiv and Hcv Transmission and Hiv Mortality at an Indonesian Narcotic Prison	Southeast Asian Journal of Tropical Medicine & Public Health	No MOUD Data
2019	Papaluca	Outcomes of treatment for hepatitis C in prisoners using a nurse-led, statewide model of care	Journal of Hepatology	No Reinfection Data
2017	Papaluca	A state-wide, nurse-led model of care for HCV in the prison: High SVR12 rates that are equivalent to the specialist liver clinic	Hepatology	No HCV Incidence Data
2017	Papaluca	Outcomes of treatment for hepatitis C virus infection in the prison setting	Journal of Gastroenterology and Hepatology (Australia)	Duplicate Study
2016	Peters	HIV testing and care in prisoners: The first year results of opt-out BBV testing in Glasgow, Uk	Journal of the International AIDS Society	No HCV Incidence Data
2010	Pham	Frequent multiple hepatitis C virus infections among injection drug users in a prison setting	Hepatology	Duplicate Study
2006	Remy	Treatment for hepatitis C in jailhouses is doable and successful: Definitive data of first national French study (POPHEC)	Heroin Addiction and Related Clinical Problems	No Reinfection Data
2012	Rice	Comparison of hepatitis C virus treatment between incarcerated and community patients	Hepatology	No Reinfection Data
2014	Saiz de la Hoya	Directly observed therapy for chronic hepatitis C: A randomized clinical trial in the prison setting	Gastroenterologia y Hepatologia	No Reinfection Data
2010	Saksena	Treating hepatitis c in prisoners: Is it worth it?	Gut	No MOUD Data
2018	Shah	Breaking free from hepatitis C-hepatitis treatment in south London prisons	Hepatology	No Reinfection Data
2016	Simonovic	Antiviral Treatment of Hepatitis C in Serbian Prison Setting: Medical Treatment Outcomes and Patients’ Adherence	Medicinski Pregled	No Reinfection Data
2014	Snow	Incidence and correlates of hepatitis C virus infection in a large cohort of prisoners who have injected drugs	BMC Public Health	Wrong Outcomes
2006	Stark	A syringe exchange programme in prison as prevention strategy against HIV infection and hepatitis B and C in Berlin, Germany	Epidemiology and Infection	Wrong Outcomes
2015	Szetoo	Outcome of Hepatitis C treatment in prison: A 10 year retrospective review	Journal of Gastroenterology and Hepatology (Australia)	Duplicate Study
2010	Teutsch	Incidence of primary hepatitis C infection and risk factors for transmission in an Australian prisoner cohort	BMC Public Health	Duplicate Study
2015	Treloar	Acquiring hepatitis C in prison: the social organisation of injecting risk	Harm Reduction Journal	Duplicate Study
2014	White	Opioid substitution therapy protects against hepatitis C virus acquisition in people who inject drugs: the HITS-c study	Medical Journal of Australia	Duplicate Study

Table 4:

Risk of Bias for Cohort Studies About MOUD Effect on HCV Incidence. Average Score 7.3

Author	Representative -ness of Exposed Cohort	Selection of the Non-Exposed Cohort	Ascertainment of Exposure	Demonstration that outcome of interest was not present at the start of the study	Comparability of cohorts on the basis of the design or analysis	Assessment of Outcome	Was follow Up long enough for outcomes to occur	Adequacy of follow up of cohorts	Total (/9)
Cunningham et al19	*	*	*	*	**	*	*	*	9
Marco et al20	*	*	*	*	*	*	*	-	7
Marco et al21	*	*	*	*	-	*	*	-	6

Table 5:

Risk of Bias for Randomized Controlled Trials About MOUD Effect on HCV Incidence

Author	Random Sequence Generation	Allocation Concealment	Selective Reporting	Other Sources of Bias	Blinding of Participants and Personnel	Blinding of Outcome Assessment	Incomplete Outcome Data
Dolan et al22	Low	Low	Low	Low	Unclear	Unclear	Low

Table 6:

Risk of Bias for Cross-Sectional Studies About MOUD Effect on HCV Incidence. Average Score 4

Author	Representativeness of Sample	Sample Size	Non-Respondents	Ascertainment of Exposure	Comparability of Different Outcome Groups	Total (/5)
Taylor et al23	*	*	*	*	-	4
Søholm et al24	*	*	*	*	-	4

Table 7:

Study Details and Outcomes

		Study Design	Participants	Study Size, Additional Information	Initial HCV prevalence	Method of HCV Incidence Evaluation	MOUD Status	Total Cohort HCV Incidence	HCV Incidence with MOUD	HCV Incidence without MOUD	Adjusted Hazard Ratio of MOUD Effect on HCV Incidence
HCV Infections
1	Cunningham et al19	Prospective observational cohort	Participants from 23 correctional centers in NSW, Australia Continuously imprisoned with lifetime IDU history OR history of tattooing, piercing, blood fights. All HCV Ab negative	320 Ab negative participants (211 in continuously imprisoned analysis) assessed from 2005 to 2014	19% on initial cohort enrollment	Biannual Ab and PCR testing	based on ‘currently receiving’ during biannual patient interview 15–20% of cohort (2005–2009)	6.30/100 PY 10/100 PY among those with active IDU in prison	11.40/100 PY	9.60/100 PY	1.32 (0.43, 4.10)
2	Dolan et al22	Randomized controlled trial	Participants in the NSW prison system with OUD (heroin) seeking MOUD treatment	191 MMT versus 191 placebo Assessed over 4 months from 19971998	72 – 76%	HCV Ab, no PCR at 4 month follow up	MMT versus waitlist (4 months)	n/a	24.30/100 PY	31.70/100 PY	0.77 (0.22, 3.56)
3	Marco et al20	Retrospective cohort	HCV seronegative participants in a single Barcelona prison	2377 participants surveilled from 1992 to 2001 Annual HCV testing offered to seronegatives. Followed post release as well	“65–99% in Spanish prisons”	HCV Ab Annual testing or with risk factors	MMT (included if continuous from enrollment to last follow up); all persons with OUD offered MMT	1.17/100 PY*	1.35/100 PY (IDU with MMT)*	6.61/100 PY (IDU without MMT)*	1.07 (0.33, 3.46)
4	Taylor et al23	Cross sectional study	Participants in 14 Scottish prisons	2446 persons evaluated with Ab and PCR from 2010 to 2011 All in prison for at least 75 days	19%	HCV Ab and PCR from dried blood spot Incidence calculated based on Ab- PCR+ participants	57% of PWID on opioid agonist treatment at time of interview	0.60–0.90/100 PY overall (in-prison transmission) 3.0–4.30/100 PY among PWID	Limited 1 participant out of 479 HCV negative PWID	Limited 2 participants out of 479 HCV negative PWID	n/a
5	Søholm et al24	Cross Sectional Study	Participants in 8 Danish prisons	801 persons evaluated with Ab and PCR from 2016 to 2017 All in prison for at least 75 days	9.40% serologic, 7.40% viremic	HCV Ab and PCR Incidence calculated based on Ab- PCR+ participants	Receipt or absence of current OST asked at time of interview 47% of PWID actively on MOUD	0.70–1.0/100 PY overall (in-prison transmission) 18.10–24.50/100 PY among PWID	35–44/100 PY	0/100 PY	n/a
HCV Reinfections
6	Marco et al21	Retrospective cohort	Participants from 4 prisons in Catalonia, Spain. All post HCV treatment (IFN based) with SVR	119 participants tested annually for reinfection from 2003–2010 Many released in interim	n/a	Annual HCV RNA PCR Genotype assessed to confirm reinfection	All persons with IDU routinely offered low dose MMT in prison. Linked on release and annually queried. 40% of those w/ IDU on MMT throughout	5.27/100 PY* 33/100 PY among active IDU	1.64/100 PY*	7.49/100 PY*	0.22 (0.06, 4.14)

Ab = Antibody; PY = Person Year; NSW = New South Wales; MMT = Methadone maintenance therapy; IDU = Injection Drug Use; PWID = people who inject drugs; IFN = Interferon; SVR = Sustained virologic response; mg = milligram

^*both continuously and non-continuously incarcerated persons

Table 8.

Study Substance Use Characteristics

		Substance Use Characteristics	Needle/Syringe Services
1	Cunningham et al19	33% of total cohort reporting IDU since entering prison 18% heroin, 4% cocaine, 14% methamphetamine Also injected methadone/buprenorphine	none bleach or quaternary amine disinfectant available
2	Dolan et al22	>80% heroin use at baseline 68% of treatment group still on MMT at 4 month follow up, 19% control subjects started MMT Average methadone dose moderate (61 mg) 40% methamphetamine use at baseline	None Bleach disinfectant available
3	Marco et al20	7% IDU	yes
4	Taylor et al23	32% with reported lifetime history of IDU Low amount of in-prison injecting “98% of Scottish PWID inject heroin”	no
5	Søholm et al24	8.5% IDU 3.6% reported injecting drugs in prison No reported info on stimulant injection at time evaluation; 85% lifetime amphetamine use	no
6	Marco et al21	81% with life history of IDU 10.1% with active IDU during study evaluation	3 out of 4 participating prisons

MMT = Methadone maintenance therapy; IDU = Injection Drug Use; PWID = people who inject drugs; IFN = Interferon; mg = milligram