Hepatitis C Virus Reinfection Research Articles

Low hepatitis C virus reinfection rate despite ongoing risk following universal access to direct-acting antiviral therapy among people living with HIV.

To evaluate changes in injecting and sexual risk behaviours, and hepatitis C virus (HCV) reinfection incidence among people with HIV/HCV coinfection following unrestricted access to direct-acting antiviral therapy in Australia. Prospective observational cohort study (2014-2018). Among people enrolled in the Control and Elimination of HCV from HIV-infected individuals within Australia study, changes in injecting and sexual behaviour were evaluated, including injecting drug use (IDU) in the last 6 months and last month, frequency of IDU and equipment sharing, condom-less anal intercourse with casual male partner(s), and group sex. HCV reinfection incidence was evaluated with follow-up through May 2018. Overall, 272 HIV/HCV antibody-positive participants [median age; 50 years, 96% male, 83% identified as gay and bisexual men (GBM)] had behavioural data at enrolment and follow-up (median 2.91 years) available for analysis. The proportion reporting IDU in the last 6 months remained stable from enrolment (35%) to follow-up (39%). Among GBM, the proportion reporting condom-less anal intercourse with casual partner(s) at enrolment (48%) and follow-up (46%) was also similar. Reinfection was detected in five individuals (all GBM) during total follow-up of 474 person-years for an overall incidence of 1.05 per 100 person-years (95% confidence interval, 0.44-2.53). No change was observed in levels of injecting or sexual risk behaviour for HCV infection following unrestricted access to direct-acting antiviral therapy in an Australian HIV/HCV cohort. Incidence of HCV reinfection was low potentially reflecting high levels of treatment coverage within this population. Continued screening and rapid retreatment of reinfection will be required to maintain progress towards elimination.

Unmet needs of chronic hepatitis C in the era of direct-acting antiviral therapy.

The treatment of chronic hepatitis C (CHC) has been revolutionized in an era of all-oral direct-acting antivirals (DAAs) since 2014. Satisfactory treatment efficacy and tolerability can be provided by novel DAAs. Nevertheless, there are still some unmet needs and emerging issues in the treatment of CHC in the DAA era. Certain hard-to-cure populations are prone to have inferior treatment responses, including patients with severe liver decompensation, active hepatocellular carcinoma (HCC), and hepatitis C virus (HCV) genotype 3 (HCV-3) infection and those who experience multiple DAA treatment failures. Hepatitis B virus (HBV) reactivation during and after DAA treatment has raised concern regarding the use of prophylactic antivirals against HBV throughout DAA treatment. However, the standard strategy for the use of prophylactic antivirals is not uniform across regional guidelines. In the post-sustained virological response (SVR) period, HCC still occurs in a substantial proportion of patients. Due to the relatively short follow-up period, the net benefit of the achievement of an SVR by DAAs in the reduction of extrahepatic manifestations has not yet been determined. Attention must also be paid to HCV reinfection, particularly in high-risk populations. The most critical and unmet need for HCV elimination is the large gap in the HCV care cascade at the population level. To accomplish the World Health Organization (WHO)’s goal for HCV elimination by 2030, the expansion of access to HCV care requires a continuous effort to overcome practical and political challenges.

Reinfection Following Successful Direct-acting Antiviral Therapy for Hepatitis C Virus Infection Among People Who Inject Drugs.

The aim of this analysis was to calculate the incidence of hepatitis C virus (HCV) reinfection and associated factors among 2 clinical trials of HCV direct-acting antiviral treatment in people with recent injecting drug use or currently receiving opioid agonist therapy (OAT). Participants who achieved an end-of-treatment response in 2 clinical trials of people with recent injecting drug use or currently receiving OAT (SIMPLIFY and D3FEAT) enrolled between March 2016 and February 2017 in 8 countries were assessed for HCV reinfection, confirmed by viral sequencing. Incidence was calculated using person-time of observation and associated factors were assessed using Cox proportional hazard models. Seventy-three percent of the population at risk of reinfection (n = 177; median age, 48 years; 73% male) reported ongoing injecting drug use. Total follow-up time at risk was 254 person-years (median, 1.8 years; range, 0.2-2.8 years). Eight cases of reinfection were confirmed for an incidence of 3.1/100 person-years (95% confidence interval [CI], 1.6-6.3) overall and 17.9/100 person-years (95% CI, 5.8-55.6) among those who reported sharing needles/syringes. Younger age and needle/syringe sharing were associated with HCV reinfection. These data demonstrate the need for ongoing monitoring and improved strategies to prevent HCV reinfection following successful treatment among people with ongoing injecting drug use to achieve HCV elimination. NCT02336139 and NCT02498015.

ITTREAT (Integrated Community Test - Stage - TREAT) Hepatitis C service for people who use drugs: Real-world outcomes.

Direct-acting antivirals (DAAs) provide an unprecedented opportunity for a "find-and-treat strategy." We aimed to report real-world clinical, patient reported and health economic outcomes of community-based hepatitis C virus (HCV) screening/treatment in people who use drugs (PWUDs). Project ITTREAT (2013-2021), established at a drug and alcohol treatment centre, offered a comprehensive service. Generic (SF-12v2 and EQ-5D-5L) and liver-specific (SFLDQoL) health-related quality of life (HRQoL) were assessed before and after HCV treatment. Costs/case detected and cured were calculated. Primary outcome measure was sustained virological response (SVR) (intention to treat). Till March 2018, 573 individuals recruited, 462 (81%) males, mean age 40.5±10.0years. Of the 125 treated, 115 (92%) had past/current history of injecting drug use, 88 (70%) were receiving opioid agonist treatment and 50 (40%) were homeless. Twenty-six per cent received interferon-based and 74% DAA-only regimens. SVR (ITT) was 87% (90% with DAAs). Service uptake/HCV treatment completion rates were >95%, HCV reinfection being 2.63/100 person years (95% CI 0.67-10.33). HRQoL improved significantly at end of treatment (EOT) in those with SVR: SFLDQoL (symptoms, memory, distress, loneliness, hopelessness, sleep and stigma) (P</=.011); SF-12 v2 physical and mental health domains (P<.001); and EQ-5D-5L composite profile score (P=.009) and visual analogue scale, P<.001. Cost (British pounds 2018) per case detected was £171; mean cost per cure (excluding medication) was £702±188. Excellent real-world SVRs in PWUDs with significant improvement in HRQoL can be achieved at modest costs. Project ITTREAT endorses community-based integrated services to help achieve HCV elimination.

Epidemiological trends in HCV transmission and prevalence in the Viennese HIV+ population.

Background & AimsHuman immunodeficiency virus (HIV)/hepatitis C virus (HCV) coinfection is common in people who inject drugs (PWIDs). Recently, ‘high‐risk’ behaviour among men who have sex with men (MSM) has emerged as another main route of HCV transmission. We analysed temporal trends in HCV epidemiology in a cohort of Viennese HIV+ patients.MethodsHepatitis C virus parameters were recorded at HIV diagnosis (baseline [BL]) and last visit (follow‐up [FU]) for all HIV+ patients attending our HIV clinic between January 2014 and December 2016. Proportions of HIV+ patients with anti‐HCV(+) and HCV viraemia (HCV‐RNA(+)) at BL/FU were assessed and stratified by route of transmission.ResultsIn all, 1806/1874 (96.4%) HIV+ patients were tested for HCV at BL. Anti‐HCV(+) was detected in 93.2% (276/296) of PWIDs and in 3.7% (31/839) of MSM. After a median FU of 6.9 years, 1644 (91.0%) patients underwent FU HCV‐testing: 167 (90.3%) of PWIDs and 49 (6.7%) of MSM showed anti‐HCV(+). Among 208 viraemic HCV‐RNA(+) patients at BL, 30 (14.4%) had spontaneously cleared HCV, 76 (36.5%) achieved treatment‐induced eradication and 89 (42.8%) remained HCV‐RNA(+) at last FU. Among 1433 initially HCV‐naive patients, 45 (3.5%) acquired de‐novo HCV infection (11.1% PWIDs/80.0% MSM; incidence rate (IR) 0.004%; 95% confidence interval [CI] 0.0%‐0.022%) and 14 had HCV reinfections (85.7% PWIDs/14.3% other; IR 0.001%; 95% CI 0.0%‐0.018%) during a median FU of 6.7 years (interquartile range 7.4).ConclusionHepatitis C virus testing was successfully implemented in the Viennese HIV(+) patients. Anti‐HCV(+) prevalence remained stable in HIV+ PWIDs but almost doubled in HIV+ MSM. De‐novo HCV infection occurred mostly in MSM, while HCV reinfections were mainly observed in PWIDs. HCV treatment uptake was suboptimal with 42.8% remaining HCV‐RNA(+) at FU.

Long-term follow-up of HCV patients with sustained virological response after treatment with pegylated interferon plus ribavirin

BackgroundThe progress of liver diseases may not stop after viral eradication. This study aimed to provide data on long-term prognosis of patients with hepatitis C virus (HCV) infection who underwent pegylated interferon plus ribavirin (PR) regimen and achieved a sustained virological response 24 weeks post-treatment (SVR24). MethodsResponders to the PR regimen in our hospital from January 2011 to June 2014 were enrolled and prospectively followed up. Baseline characteristics were profiled. The incidence of hepatocellular carcinoma (HCC), progression of liver disease (increase in liver stiffness or occurrence of decompensated complication), and HCV recurrence was all monitored. The accumulative and annualized incidence rates (AIRs) of these adverse events were analyzed, and the risk factors were also examined. ResultsIn total, 151 patients reached a median follow-up time of 103 weeks. Among them, two had an incidence of HCC during the surveillance with AIR of 0.68% (95% CI: 0.00-1.63%). Six patients showed progression of liver disease with AIR of 2.05% (95% CI: 0.42%-3.68%). Three patients who had risky behaviors encountered HCV reinfection. The cirrhotic patients faced higher risk of poor prognosis than non-cirrhotic patients, including HCC and progression of liver disease (AIR: 6.17% vs. 1.42%, P = 0.039). ConclusionsThe incidence of HCC and progression of liver disease was evident in PR responders during the long-term follow-up period, but the risk level was low. Cirrhotic responders were more vulnerable to develop HCC post SVR24 compared with non-cirrhotic ones. HCV recurrence was rare in responders with SVR24 who had corrected their risky behaviors.

Acute hepatitis C infection among adults with HIV in the Netherlands between 2003 and 2016: a capture-recapture analysis for the 2013 to 2016 period.

BackgroundWith regards to the global strategy towards eliminating viral hepatitis, reliable surveillance systems are essential to assess the national response for eliminating hepatitis C virus (HCV).AimWe aimed to assess the completeness of the two national registries with data on acute HCV infection in people with HIV, and estimated the number of acute HCV infections among adults (aged ≥ 18 years) with HIV in the Netherlands.MethodsIn this observational study, cases of HCV infection and reinfection among adults with a positive or unknown HIV-serostatus were identified from 2003 to 2016 in two national registries: the ATHENA cohort and the National Registry for Notifiable Diseases. For 2013–2016, cases were linked, and two-way capture–recapture analysis was carried out.ResultsDuring 2013–2016, there were an estimated 282 (95% confidence interval (CI): 264–301) acute HCV infections among adults with HIV. The addition of cases with an unknown HIV-serostatus increased the matches (from n = 107 to n = 129), and subsequently increased the estimated total: 330 (95%CI: 309–351). Under-reporting was estimated at 14–20%.ConclusionUnder-reporting of acute HCV infection among people with HIV could partially be explained by an unknown HIV-serostatus, or by differences in HCV stage (acute or chronic) at first diagnosis. Surveillance data should ideally include both acute and chronic HCV infections, and enable to distinguish these as well as initial- and re-infections. National surveillance of acute HCV can be improved by increased notification of infections.

Economic Evaluation of Hepatitis C Treatment Extension to Acute Infection and Early-Stage Fibrosis Among Patients Who Inject Drugs in Developing Countries: A Case of China.

We aimed to assess the cost-effectiveness of (1) treating acute hepatitis C virus (HCV) vs. deferring treatment until the chronic phase and (2) treating all chronic patients vs. only those with advanced fibrosis; among Chinese genotype 1b treatment-naïve patients who injected drugs (PWID), using a combination Daclatasvir (DCV) plus Asunaprevir (ASV) regimen and a Peg-interferon (PegIFN)-based regimen, respectively. A decision-analytical model including the risk of HCV reinfection simulated lifetime costs and quality-adjusted life-years (QALYs) of three treatment timings, under the DCV+ASV and PegIFN regimen, respectively: Treating acute infection (“Treat at acute”), treating chronic patients of all fibrosis stages (“Treat at F0 (no fibrosis)”), treating only advanced-stage fibrosis patients (“Treat at F3 (numerous septa without cirrhosis)”). Incremental cost-effectiveness ratios (ICERs) were used to compare scenarios. “Treat at acute” compared with “Treat at F0” was cost-saving (cost: DCV+ASV regimen—US$14,486.975 vs. US$16,224.250; PegIFN-based regimen—US$19,734.794 vs. US$22,101.584) and more effective (QALY: DCV+ASV regimen—14.573 vs. 14.566; PegIFN-based regimen—14.148 vs. 14.116). Compared with “Treat at F3”; “Treat at F0” exhibited an ICER of US$3780.20/QALY and US$15,145.98/QALY under the DCV+ASV regimen and PegIFN-based regimen; respectively. Treatment of acute HCV infection was highly cost-effective and cost-saving compared with deferring treatment to the chronic stage; for both DCV+ASV and PegIFN-based regimens. Early treatment for chronic patients with DCV+ASV regimen was highly cost-effective.

Hepatitis C virus (HCV) care in Canadian correctional facilities: Whereare we and where do we need to be?

Approximately 25% of people in Canadian correctional facilities have been previously exposed to hepatitis C virus (HCV). Despite being a high-prevalence setting, most Canadian prisons have thus far failed to engage the majority of those with chronic HCV infection in care. Several factors, including the lack of systematic screening programs, lack of on-site and trained health care personnel to improve access to care and treatment during incarceration, and the absence of standardized procedures needed to facilitate linkage to care following release likely contribute to poor engagement along the HCV care cascade for people in prison. HCV screening and engagement in care for people in prison can be improved through the implementation of universal opt-out screening upon admission and consideration of multidisciplinary care models for the provision of care. As well, the dissemination of prison-based needle and syringe programs to avert new HCV infections and re-infections should be considered. To meet the World Health Organization (WHO) 2030 HCV elimination goals, engaging researchers, clinicians and other health care providers, policy makers, correctional officials, and members of community in dialogue will be an essential first step going forward.

Hepatitis C reinfection with protease inhibitor-resistant hepatitis C virus in an HIV-coinfected MSM.

There is an ongoing global hepatitis C virus (HCV) epidemic mainly related to high-risk behaviour in persons who inject drugs (PWID) and in HIV-infected men who have sex with men (MSM) which continues to fuel the HCV epidemic. Treatment of HCV infection with direct antiviral therapy (DAA) has been very successful in the last decade. Main obstacles for HCV elimination are HCV reinfections observed in PWID and HIV-infected MSM. We present here an HIV-infected MSM patient who has been reinfected thrice with HCV. The virus which was investigated from his last reinfection episode reveals transmission of a newly acquired HCV protease inhibitor (PI) resistance, despite not having been exposed to HCV-PIs during his last DAA therapy.

Rationale and design of a randomized pragmatic trial of patient-centered models of hepatitis C treatment for people who inject drugs: The HERO study

BackgroundAlthough people who inject drugs (PWID) having the highest incidence and prevalence of hepatitis C virus (HCV) in the US, HCV treatment is rarely provided to PWID due to assumptions about poor adherence and reinfection risk. As direct-acting antiviral agents (DAAs) have achieved sustained virologic response (SVR) rates of 95% or more, evidence-based strategies are urgently needed to demonstrate real-world effectiveness in marginalized patient populations such as PWID. The objectives of this study are: 1) to determine whether either of two patient-centered treatment models – patient navigation (PN) or modified directly observed therapy (mDOT) – results in more forward movement along the HCV care cascade including treatment initiation, adherence, and SVR; 2) using quantitative and qualitative methods, to understand factors associated with lack of treatment uptake, poor adherence (<80%), failure to achieve SVR, DAA resistance, and HCV reinfection. MethodsThe HERO study is a multi-site, pragmatic randomized clinical trial conducted in eight states where 754 HCV-infected PWID were randomly assigned to either PN or mDOT. ConclusionsThis study addresses an urgent need for timely and accurate information on optimal models of care to promote HCV treatment initiation, adherence, treatment completion and SVR among PWID, as well as rates and factors associated with reinfection and resistance after treatment. This clinical trial has the potential to provide valuable information on how to reduce the burden of the HCV epidemic in PWID.

Reinfection With the Hepatitis C Virus in Men Who Have Sex With Men After Successful Treatment With Direct-acting Antivirals in Germany: Current Incidence Rates, Compared With Rates During the Interferon Era.

Micro-elimination of the hepatitis C virus (HCV) includes treatment in populations at risk of ongoing HCV transmission, such as men who have sex with men (MSM) or people who inject drugs (PWID). We analyzed the HCV reinfection incidence rates of participants in the German hepatitis C cohort (GECCO) and compared our data to previous findings from the interferon era. Patients with HCV reinfections in the multi-centric GECCO cohort were compared to patients in whom no reinfection occurred. The HCV reinfection incidence rate in MSM was also compared to the incidence rate in the interferon era (using data from the European Acquired Immunodeficiency Syndrome Treatment Network [NEAT]). Between January 2014 and April 2018, 48 HCV reinfections occurred in 2298 individuals (2%), with 2346 cured HCV episodes. The median time to reinfection was 500 days (range 16-1160) and the overall HCV reinfection incidence rate was 1.89 per 100 person-years (py; 95% confidence interval [CI], 1.41-2.48). In a multivariate analysis, the transmission risk in MSM was the only independent risk factor of HCV reinfection (odds ratio, 39.3; 95% CI, 4.57-334.40; P = .001). The incidence rate in MSM was 9.02 (95% CI, 6.48-12.26) per 100 py, compared to 1.14 per 100 py in PWID (95% CI, .56-2.09). The incidence rate for a first HCV reinfection in MSM was similar in the direct-acting antiviral era, compared to the interferon era, with a hazard ratio of 1.05 (95% CI, .64-1.74; P = .831). HCV reinfection remains a frequent finding among MSM in Germany. In addition to behavioral interventions, early HCV treatment and retreatment should be implemented for this subgroup to prevent HCV transmission.

Efficacy of Direct-acting Antivirals for Chronic Hepatitis C Virus Infection in People Who Inject Drugs or Receive Opioid Substitution Therapy: A Systematic Review and Meta-analysis.

Treatment uptake for hepatitis C virus (HCV) infection in people who inject drugs (PWID) and patients on opioid substitution therapy (OST) is still low despite treatment guidelines that advocate the use of direct-acting antivirals (DAAs) in all patients. Our aim in this review was to investigate treatment outcomes among PWID and patients on OST in comparison to control cohorts. A search of Embase, Medline, PubMed, and Web of Science (from October 2010 to March 2018) was conducted to assess sustained virologic response (SVR), discontinuation rates, adherence, and HCV reinfection in PWID and patients on OST. We identified 11 primary articles and 12 conference abstracts comprising 1702 patients on OST, 538 PWID, and 19 723 patients who served as controls. Among patients on OST, the pooled SVR was 90% (95% confidence interval [CI], 87% to 93%) and pooled treatment discontinuation rate was 7% (95% CI, 4% to 11%). Similarly, the pooled SVR was 88% (95% CI, 80% to 93%) in PWID and the pooled treatment discontinuation rate was 9% (95% CI, 5% to 15%). There was no significant difference regarding pooled rates of SVR, adherence, and discontinuation between patients on OST and controls as well as between PWID and controls. HCV reinfection rates among patients on OST ranged from 0.0 to 12.5 per 100 person-years. HCV treatment outcomes in PWID and patients on OST are similar to those in patients without a history of injecting drugs, supporting current guideline recommendations to treat HCV in these patient populations.

HCV reinfections after viral clearance among HIV-positive patients with recent HCV infection in Taiwan.

Higher rates of hepatitis C virus (HCV) reinfection after viral clearance have been well described among HIV-positive men who have sex with men (MSM) in Europe. The epidemiology of HCV reinfection, however, has rarely been investigated among HIV-positive patients in Asia-Pacific region. We retrospectively identified HIV-positive patients with recent HCV infection who had cleared their primary infection, either spontaneously or via treatment, between January 2011 and May 2018. All included patients were observed until 31 March 2019. HCV reinfection was defined as recurrent HCV viraemia after achieving viral clearance with anti-HCV treatment or after spontaneous clearance. During the study period, 219 HIV-positive patients (90.4% MSM) were diagnosed with recent HCV infection. Viral clearance with successful treatment was achieved in 108 patients (49.3%) and spontaneous clearance occurred in 20 (9.1%); of them, 18 (14.1%) acquired HCV reinfections, resulting in an incidence rate of 8.2 per 100 person-years of follow-up (95% CI 5.2-13.1). With the adjusted Cox proportional hazards model, we found a higher reinfection risk in patients with syphilis (adjusted hazard ratio 10.3, 95% CI 1.4-77.8, P=.023) compared to those without syphilis. HCV RNA testing, if performed only following syphilis and elevated aminotransferases, might miss 44.4% and 33.3% of HCV reinfections, respectively. Similar to the findings in Europe, we observed a high incidence of HCV reinfection among HIV-positive Taiwanese with recent HCV infection, which was significantly associated with syphilis. To identify HCV reinfections, annual HCV RNA testing should be instituted instead of testing driven by symptoms, syphilis or elevated aminotransferases.

Low Hepatitis C Reinfection Following Direct-acting Antiviral Therapy Among People Who Inject Drugs on Opioid Agonist Therapy.

Direct-acting antiviral (DAA) therapy is highly effective in people who inject drugs (PWID); however, rates, specific injection behaviors, and social determinants associated with hepatitis C virus (HCV) reinfection following DAA therapy among PWID on opioid agonist therapy (OAT) are poorly understood. PREVAIL was a randomized controlled trial that assessed models of HCV care for 150 PWID on OAT. Those who achieved sustained virologic response (SVR) (n = 141; 94%) were eligible for this extension study. Interviews and assessments of recurrent HCV viremia occurred at 6-month intervals for up to 24 months following PREVAIL. We used survival analysis to analyze variables associated with time to reinfection. Of 141 who achieved SVR, 114 had a least 1 visit in the extension study (62% male; mean age, 52 years). Injection drug use (IDU) was reported by 19% (n = 22) in the extension study. HCV reinfection was observed in 3 participants. Over 246 person-years of follow-up, the incidence of reinfection was 1.22/100 person-years (95% CI, 0.25-3.57). All reinfections occurred among participants reporting ongoing IDU. The incidence of reinfection in participants reporting ongoing IDU (41 person-years of follow-up) was 7.4/100 person-years (95% CI, 1.5-21.6). Reinfection was associated with reporting ongoing IDU in the follow-up period (P < .001), a lack confidence in the ability to avoid contracting HCV (P < .001), homelessness (P = .002), and living with a PWID (P = .007). HCV reinfection was low overall, but more common among people with ongoing IDU following DAA therapy on OAT, as well as those who were not confident in the ability to avoid contracting HCV, homeless, or living with a PWID. Interventions to mediate these risk factors following HCV therapy are warranted.

Elimination of hepatitis C virus infection among people who use drugs: Ensuring equitable access to prevention, treatment, and care for all

There have been major strides towards the World Health Organization goal to eliminate hepatitis C virus (HCV) infection as a global public health threat. The availability of simple, well-tolerated direct-acting antiviral therapies for HCV infection that can achieve a cure in >95% of people has provided an important tool to help achieve the global elimination targets. Encouragingly, therapy is highly effective among people receiving opioid agonist therapy and people who have recently injected drugs. Moving forward, major challenges include ensuring that new infections are prevented from occurring and that people who are living with HCV are tested, linked to care, treated, receive appropriate follow-up, and have equitable access to care. This editorial highlights key themes and articles in a special issue focusing on the elimination of HCV among people who inject drugs. An overarching consideration flowing from this work is how to ensure equitable access to HCV treatment and care for all. This special issue maps the field in relation to: HCV prevention; the cascade of HCV care; strategies to enhance testing, linkage to care, and treatment uptake; and HCV treatment and reinfection. In addition, papers draw attention to the ‘risk environments’ and socio-ecological determinants of HCV acquisition, barriers to HCV care, the importance of messaging around the side-effects of new direct-acting antiviral therapies, the positive transformative potential of treatment and cure, and the key role of community-based drug user organizations in the HCV response. While this special issue highlights some successful efforts towards HCV elimination among people who inject drugs, it also highlights the relative lack of attention to settings in which resources enabling elimination are scarce, and where elimination hopes and potentials are less clear, such as in many low and middle income countries. Strengthening capacity in areas of the world where resources are more limited will be a critical step towards ensuring equity for all so that global HCV elimination among PWID can be achieved.

High rates of early HCV reinfection after DAA treatment in people with recent drug use attended at mobile harm reduction units

Background and AimsThe World Health Organization recently called for the elimination of hepatitis C virus (HCV) and has identified people who inject drugs (PWID) as a key target population. Clinical trials analyzing currently available all-oral regimens have demonstrated a high degree of efficacy in this population, with a relatively low reinfection rate. There is an urgent need to confirm these data in a harm reduction and active consumption setting. The primary aim of this study was to evaluate the HCV reinfection rate in people with recent drug use followed at low-threshold mobile harm reduction units. MethodWe included people with recent drug use (smoked or injected heroin/cocaine in the previous 6 months) who received HCV treatment and were attended at two low-threshold mobile harm reduction units over 19 months. Sustained virologic response was assessed 12 weeks after therapy (SVR12). The incidence density of HCV reinfection was defined as the number of reinfections per 100-person years (PY) using person-time of observation and was stratified by drug consumption at initiation of HCV treatment. Cox proportional hazard regression analysis was used to assess factors associated with reinfection. ResultsDuring the study period, 160 people who used drugs in the past 6 months completed HCV therapy. 122 (73.9%) and 88 (53.3%) reported injecting drug use in the 6 months and 30 days prior to HCV treatment, respectively. The overall SVR12 was 68% in the ITT analysis (reinfection = failure) and 90.7% in the modified intent-to-treat analysis (considering reinfections as response and removing people who were missing SVR data). The cohort at-risk for reinfection (n = 121) included 47 (39.2%) people who initiated HCV treatment with recently reported abstinence. Reinfection was identified in 10 persons (8.3%), and the median time to reinfection was 7.2 (IQR 4.2–18) months. Total follow-up time at-risk was 101.1-PY (median 0.6 years, IQR 0.3–1.3). The overall incidence of reinfection was 9.8 per 100-PY (95% CI 4.7,18.2). The incidence of reinfection was higher amongst those who had injected drugs in the previous 6 months (16.7 [95%CI 8.0; 30.7] per 100-PY) and in the previous 30 days (18.9 [95% CI 8.1; 37.2] per 100-PY). In the adjusted analysis, only injecting drugs use in the month prior to initiation of HCV therapy was associated with reinfection (aHR 8.7, 95%CI 1.0; 73.6; p 0.04). ConclusionHigh efficacy of HCV treatment, was found in people with recent drug use attended and followed at low-threshold mobile harm reduction units. The high rate of early HCV reinfections in this setting should promote surveillance for reinfection at 7-month intervals after ending the treatment or earlier.

Direct-acting antiviral treatment for hepatitis C, reinfection and mortality among people attending an inner-city community health centre in Victoria, Canada

BackgroundDirect-acting antiviral (DAA) treatment for hepatitis C virus (HCV) has been shown to be effective among PWID, but more real-world data on treatment outcomes is needed. The aim of this analysis was to assess the efficacy of DAA therapy, and the rate of reinfection and mortality among people attending an inner-city community health centre in Victoria, Canada. MethodsIn this retrospective study, patients treated with DAA therapy between November 2014 and Dec 31, 2017 were included. Retrospective chart review was performed to assess recent injecting drug use (IDU, previous six months) or receipt of opioid agonist treatment (OAT). The primary endpoint was Sustained Virologic Response (SVR12). Secondary endpoints included HCV reinfection and mortality. ResultsOf 270 patients who initiated DAA treatment (31% female), 20% (n=54) had HIV/HCV coinfection, 32% (n=84) had cirrhosis, 67% (n=181) had genotype 1, 6% (n=15) had genotype 2, 26% (n=69) had genotype 3. 46% (n=125) of patients were receiving OAT and 49% (n=132) reported recent IDU. 98% (n=265) completed treatment; two people stopped due to mental health, two people died, and one was non-adherent. 92% (249 of 270) achieved SVR12. 16 patients with End of Treatment (EOT) response did not have a SVR12; 7 were lost to follow-up; 2 people refused bloodwork; 2 people died; 1 had reinfection; and 4 had viral relapse. There was no difference in SVR12 by OAT (OAT, 93% vs. no OAT, 91%, P=0.435), recent injecting drug use (yes, 92% vs. no, 92%, P=0.904), or HIV status (HIV, 92% vs. no HIV, 94%, P=0.498). Eight cases of HCV reinfection were observed over 253 person-years of follow up (3.2 cases per 100 person-years; 95% CI 1.6-6.3). Twenty people died (6.3 per 100 person-years; 95% CI 3.9-10.3), including two during therapy (drug overdose, n=2) and 18 following therapy completion (drug overdose, n=7). ConclusionThis study demonstrates that DAA treatment is effective among a marginalized population receiving care in an inner-city community health centre. The high mortality in this study highlights the importance of integrating HCV care within a framework addressing drug-related harms, preventing overdose mortality, addressing social inequalities, and improving the health of PWID.

Reinfection in a large cohort of prison inmates with sustained virological response after treatment of chronic hepatitis C in Catalonia (Spain), 2002–2016

BackgroundPrisoners and other high-risk patients who show a sustained virological response (SVR) after treatment for hepatitis C virus (HCV) can become reinfected. We aimed to calculate the rate of HCV reinfection in a large cohort of inmates with SVR and to determine factors that predict reinfection. MethodsWe included all inmates treated for hepatitis C in Catalonia (Spain) from January 2002 to December 2016 who achieved SVR and in whom viral load was subsequently determined. The incidence rate was calculated per 100 person-years (100 py) of follow up. Risk factors associated with reinfection were evaluated by bivariate log-rank test and multivariate Cox regression. Hazard ratio (HR) and their 95% confidence intervals (CI) were calculated. Results602 patients were included, with a mean age of 37.9 years: 95% were men, 74.1% had a history of intravenous drug use (IDU) and 28.7% were HIV-infected. Patients were followed for a total of 2154.9 years (average 3.58 ± 3.1 years). 63 (10.5%) had HCV reinfection. 41 (65.1%) presented different genotype/subgenotype, 8 the initial genotype/subgenotype, and in 14 (22.2%) the genotype could not be determined. Of the 21 reinfected patients who were interviewed, 20 (95.2%) reported IDU after antiviral treatment, and 7 (33.3%) during treatment. The overall incidence of reinfection was 2.9 cases per 100 py. All reinfections occurred in patients with IDU history. At multivariate level, HIV infection was associated with reinfection (HR = 3.03; CI:1.82-5.04). ConclusionIn HIV-infected inmates with IDU history, the rate of reinfection of HCV post-SVR is very high. Prisons play a key role in the detection and treatment of infection and reinfection by HCV and in the post-treatment monitoring in these patients, which should be combined with counseling and the optimization of the harm reduction programs. Effective control of these vulnerable groups favours the elimination of the HCV infection.

Primary Incidence of Hepatitis C Virus Infection Among HIV-Infected Men Who Have Sex With Men in San Diego, 2000-2015.

BackgroundLittle is known about the hepatitis C virus (HCV) epidemic among HIV-infected men who have sex with men (HIV+ MSM) in the United States. In this study, we aimed to determine the incidence of primary HCV infection among HIV+ MSM in San Diego, California.MethodsWe performed a retrospective cohort analysis of HCV infection among HIV+ MSM attending 2 of the largest HIV clinics in San Diego. Incident HCV infection was assessed among HIV+ MSM with a negative anti-HCV test and subsequent HCV test between 2000 and 2017, with data censored to 2015. HCV reinfection was assessed among HIV+ MSM successfully treated for HCV between 2008 and 2015. Infection/reinfection rates were calculated using person-time methods.ResultsAmong 3068 initially HCV-seronegative HIV+ MSM, 178 new infections occurred over 15 796 person-years, giving an incidence of 1.13 per 100 person-years (/100py; 95% confidence interval [CI], 0.97–1.31). Incidence was stable from 2000 to 2014 (0.83/100py; 95% CI, 0.41–1.48), with an increase to 3.01/100py (95% CI, 1.97–4.42) in 2015 (P = .02). Among 43 successfully treated patients, 3 were reinfected.ConclusionsHCV incidence is high among HIV+ MSM in San Diego, with evidence suggesting a recent increase in 2015. Strong HCV testing guidelines and active prevention efforts among HIV+ MSM are urgently needed that include rapid diagnosis, treatment, and risk reduction.