Direct-acting antiviral treatment for chronic hepatitis C in people who use drugs in a real-world setting.

BACKGROUND: Direct-acting antivirals (DAAs) offer high cure rates in people who inject drugs (PWID) with hepatitis C virus (HCV) infection. There are concerns regarding lower response rates among PWID in real life. We evaluated the outcome of DAA therapy in PWID in a real-world setting and the factors that affect it. METHODS: We performed a retrospective analysis of 174 PWID with chronic hepatitis C who started DAAs in a Greek liver clinic in collaboration with an addiction program. Patients who did not return for reassessment were considered as lost to follow up (LTFU). A logistic regression model was used to assess factors associated with a sustained virological response 12 weeks after treatment completion (SVR12) and LTFU. RESULTS: Patients' mean age was 48±9.2 years and 91/174 (52.3%) were attending opioid substitution treatment programs. Overall, 144/174 (82.8%) patients completed therapy and presented for SVR12 testing, 8/174 (4.6%) did not complete treatment and 22/174 (12.6%) were LTFU. Overall SVR12 was 79.9% (139/174). For those with an available SVR12 test the response rate reached 96.5% (139/144). Regression analysis did not indicate any significant association between patient characteristics and SVR12. Age <45 years and genotype 3 were independent predictors of LTFU. Parallel use was found to have a trend towards LTFU. CONCLUSIONS: HCV treatment by hepatologists and addiction specialists is feasible, effective and safe in a real-world setting. However, as 12% of patients appear to be LTFU, more emphasis should be placed on interventions guaranteeing follow up for SVR testing and general care.

Design and Development of a Viral Hepatitis and HIV Infection Screening Program (Hprolipsis) for the General, Greek Roma, and Migrant Populations of Greece: Protocol for Three Cross-Sectional Health Examination Surveys.

BACKGROUND: Although infectious diseases are globally on the decline, they remain a major global public health problem. Among them, the hepatitis B virus (HBV) or hepatitis C virus (HCV) and HIV infection are of primary interest. Valid prevalence data on these infections are sparse in Greece, especially for vulnerable populations. OBJECTIVE: This study aimed to present the design and methods of Hprolipsis, an integrated viral hepatitis and HIV screening program administered to adults (≥18 years) from the general, Greek Roma, and migrant populations. Its aims were to estimate the prevalence of HBV, HCV, and HIV; assess infectious disease knowledge level; design, implement, and assess population-specific awareness actions; and offer individual counseling and referral when indicated and HBV vaccination to susceptible Roma and migrants. METHODS: Multistage, stratified, random sampling based on the 2011 Census was applied to select the general population sample, and nonprobability multistage quota sampling was used for Roma and migrant sample selection. Trained personnel made home (general population) or community (Roma and migrants) visits. Collected blood samples were tested for Hepatitis B surface Antigen, Hepatitis B core Antibody, Hepatitis B surface Antibody, Hepatitis C Antibody, and HIV 1,2 Antibody. The surveys were conducted during May 2013 and June 2016. To estimate an HCV prevalence of 1.5% with 0.3 precision, the required general population sample size was estimated to be 6000. As migrants constitute 10% of the whole Greek population, the migrant sample size was set to 600. A feasible sample size of 500 Greek Roma was set. RESULTS: In total, 6006 individuals from the general population (response rate 72%), 534 Greek Roma, and 612 migrants were recruited. Blood test results are available for 4245 individuals from the general population, 523 Roma, and 537 migrants. CONCLUSIONS: Hprolipsis is the first nationwide survey on HBV, HCV, and HIV. Its results will enhance our understanding of the health needs and disease burden of these diseases in the 3 studied populations. Its implementation provided useful recommendations for future studies, particularly in vulnerable populations. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/13578.

A hepatitis C outbreak preceded the HIV outbreak among persons who inject drugs in Athens, Greece: Insights from a mathematical modelling study.

People who inject drugs (PWID) comprise one of the major transmission risk groups for human immunodeficiency virus (HIV) and hepatitis C virus (HCV). In 2011, Athens experienced a large HIV outbreak among PWID. Significant public health interventions were implemented in response to the HIV outbreak. The aims of this study were to estimate the indirect effects of the HIV interventions on HCV infection and to evaluate the concept of the association between HCV and HIV infections in the case of Athens. A dynamic, stochastic, individual-based model was developed to simulate HCV transmission among PWID. We calibrated the model to reproduce the observed HCV prevalence among PWID in Greece. Two years prior to the HIV outbreak, an undetected HCV outbreak has occurred. In 2009, the incidence of HCV infection increased from 640 (495, 842) cases in 2008 to 1260 (1060, 1500). The mean time from initiation of injecting drug use to HCV acquisition decreased from 29 months in 2008 to 13 months in 2009. After HIV interventions, HCV incidence declined by 64.8% in 2012, compared to 2009. The averted HCV incidence cases attributed to the HIV-implemented interventions were 2200 (1950, 2480), during 2012-2015. The cumulative number incident HCV cases in Athens during 2002-2015 was about 9900 (7800, 12 100). Our results highlight that before the 2011 HIV outbreak in Athens, an HCV outbreak occurred in 2009. Prevention measures for HIV that took place in the Athens metropolitan area in 2012 reduced significantly the incidence of HCV.

Aiming towards hepatitis C virus elimination in Greece.

There are estimated to be 74,000-134,000 patients living with chronic hepatitis C in Greece, but only 20-30% of them are aware of their disease status. In July 2017, the Hellenic National Plan for Hepatitis C was announced in alignment with the World Health Organization goals for the eradication of hepatitis C virus (HCV) by the year 2030. This article discusses the epidemiology and current treatment of chronic hepatitis C in Greece. Additionally the authors propose actions on how to bring back to care diagnosed patients lost to follow up, optimize access to care for HCV-infected people who inject drugs, and increase HCV screening in the general population. The medical community in Greece can play a pivotal role in the implementation of the HCV National Plan and in the efforts to reach the goal of HCV elimination.

The Effect of Interrupted/Deferred Antiretroviral Therapy on Disease Risk: A SMART and START Combined Analysis.

Background: Pooled data from the SMART and START trials were used to compare deferred/intermittent versus immediate/continuous antiretroviral therapy (ART) on disease risk. Methods: Endpoints assessed were AIDS, serious non-AIDS (SNA), cardiovascular disease (CVD), cancer, and death. Pooled (stratified by study) hazard ratios (HRs) from Cox models were obtained for deferred/intermittent ART versus immediate/continuous ART; analyses were conducted to assess consistency of HRs across baseline-defined subgroups. Results: Among 10156 participants, there were 124 AIDS, 247 SNA, 117 cancers, 103 CVD, and 120 deaths. Interventions in each trial led to similar differences in CD4 count and viral suppression. Pooled HRs (95% confidence interval) of deferred/intermittent ART versus immediate/continuous ART were for AIDS 3.63 (2.37-5.56); SNA 1.62 (1.25-2.09); CVD 1.59 (1.07-2.37); cancer 1.93 (1.32-2.83); and death 1.80 (1.24-2.61). Underlying risk was greater in SMART than START. Given the similar HRs for each trial, absolute risk differences between treatment groups were greater in SMART than START. Pooled HRs were similar across subgroups. Conclusions: Treatment group differences in CD4 count and viral suppression were similar in SMART and START. Likely as a consequence, relative differences in risk of AIDS and SNA between immediate/continuous ART and deferred/intermittent ART were similar. Clinical Trials Registration: NCT00027352 and NCT00867048.

Clinical and epidemiological characteristics of hepatitis C virus-infected people who inject drugs: a Greek descriptive analysis.

BACKGROUND: It is estimated that 17,000 people who inject drugs (PWID) in Greece have hepatitis C virus (HCV) viremia. The aim of our study was to explore the characteristics of the HCV-infected, direct acting antiviral (DAA)-naïve PWID. METHODS: This is a retrospective analysis of PWID with HCV infection. We selected data from six liver clinics during the period from 1st May 2014 to 31st May 2017 in order to record the characteristics of infected PWID. RESULTS: We included 800 PWID with HCV infection (78.5% male, mean age 42±10 years) who had not received DAAs before 1st June 2017. One third of the patients had comorbidities (diabetes mellitus, arterial hypertension and psychological disorders); 70% were smokers, 27% alcohol users, 67% unemployed, 29% married, and 34% had education >12 years; 65% were attending addiction programs; 57% were receiving methadone and 36% buprenorphine. Sporadic or systemic drug use was reported by 37% while 1.4% and 2.9% had HIV and HBV coinfection, respectively. The genotype distribution was 20.5%, 4.6%, 3.3%, 61% and 10% for genotypes 1a, 1b, 2, 3 and 4, respectively. Mean (±SD) liver stiffness was 9±7 kPa and 21% of the patients had cirrhosis. Half of the patients were in the F0-F1 stage of liver disease, defined as stiffness ≤7 kPa. CONCLUSIONS: Our real-life data suggest that HCV genotype 3 remains the predominant genotype among PWID. One third of PWID had comorbidities and one-fifth cirrhosis. Half of PWID had early-stage liver disease and remained without access to DAAs according to the Greek prioritization criteria.

Treatment and primary prevention in people who inject drugs for chronic hepatitis C infection: is elimination possible in a high-prevalence setting?

AIMS: To project the impact of scaling-up oral anti-viral therapy and harm reduction on chronic hepatitis C (CHC) prevalence and incidence among people who inject drugs (PWID) in Greece, to estimate the relationship between required treatment levels and expansion of harm reduction programmes to achieve specific targets and to examine whether hepatitis C virus (HCV) elimination among PWID is possible in this high-prevalence setting. DESIGN: A dynamic discrete time, stochastic individual-based model was developed to simulate HCV transmission among PWID incorporating the effect of HCV treatment and harm reduction strategies, and allowing for re-infection following treatment. SETTING/PARTICIPANTS: The population of 8300 PWID in Athens Metropolitan area. MEASUREMENTS: Reduction in HCV prevalence and incidence in 2030 compared with 2016. FINDINGS: Moderate expansion of HCV treatment (treating 4-8% of PWID/year), with a simultaneous increase of 2%/year in harm reduction coverage (from 44 to 72% coverage over 15 years), was projected to reduce CHC prevalence among PWID in Athens by 46.2-94.8% in 2030, compared with 2016. CHC prevalence would reduce to below 10% within the next 4-5 years if annual HCV treatment numbers were increased up to 16-20% PWID/year. The effect of harm reduction on incidence was more pronounced under lower treatment rates. CONCLUSIONS: Based on theoretical model projections, scaled-up hepatitis C virus treatment and harm reduction interventions could achieve major reductions in hepatitis C virus incidence and prevalence among people who inject drugs in Athens, Greece by 2030. Chronic hepatitis C could be eliminated in the next 4-5 years by increasing treatment to more than 16% of people who inject drugs per year combined with moderate increases in harm reduction coverage.

Substitution treatment or active intravenous drug use should not be contraindications for antiviral treatment in drug users with chronic hepatitis C.

INTRODUCTION AND AIMS: International guidelines and routine clinical practice express concerns about antiviral treatment in intravenous drug users (IDUs). We analysed the effect of IDU and/or substitution therapy on chronic hepatitis C (CHC) treatment adherence and response. PATIENTS AND METHODS: Intravenous drug users with CHC were divided into three groups: (A) patients on a substitution programme; (B) active users; and (C) past IDUs. Patients were treated according to the standard of care and followed by a specialist team. RESULTS: A total of 175 patients (mean age 39.4±8.8) were included. One hundred and forty-four (65%) were adherent to therapy (completing treatment and 6 months of follow-up). Twenty-two patients (36%) discontinued because of side effects, 28 (46%) discontinued on their own and 11 (18%) completed treatment but did not present at follow-up. Of 142 patients with available treatment outcome, 99 (69.7%) achieved a sustained virological response (SVR), with no differences among the study groups. Patients with genotypes 2-3 and those who completed the treatment schedule had 2.78-fold (95% CI: 1.3-5.8) and 6.4-fold (95% CI: 2.6-15.6) higher probability of achieving SVR. CONCLUSION: Active use of illicit drugs and/or drug substitution do not affect the treatment outcome in patients with CHC as long as they are closely followed and remain adherent to the treatment.

Peginterferon/ribavirin treatment achieves a higher compliance rate than interferon/ribavirin combination in patients chronically infected with HCV on methadone maintenance.

INTRODUCTION: Chronic hepatitis C virus infection (HCV) is the most common infectious disease among intravenous drug users. AIMS: To determine and compare compliance rates between two groups of chronic HCV patients from the methadone substitution program of the National Greek Organization Against Drugs treated with either pegylated interferon alpha-2b/ribavirin or with interferon alpha-2b/ribavirin during 48 weeks of therapy and 24 weeks of follow-up. Furthermore, to evaluate the efficacy of each treatment modality. METHODS: Forty-five consecutive methadone maintenance (MM) patients (group A, 36 males, nine females) were treated with pegylated interferon alpha-2b (weight-based dosing 1.5 microg/kg/week) and ribavirin 1000-1200 mg/day orally. Sixty-five consecutive MM patients (group B, 52 males, 13 females) were treated with interferon alpha-2b (6 MIU, three times/week) and ribavirin with the doses reported above. During the study, all patients were followed up periodically by hepatologists, internists, and psychiatrists. RESULTS: Baseline characteristics were similar between the two groups. Thirty-four out of 45 patients (75.6%) from group A and 31 of 65 patients (47.7%) from group B completed therapy (P =0.006). Thirty-two (71.1%) patients from group A and 27 patients (41.5%) from group B were followed-up until the end of week 72 (P = 0.004). At the end of the follow-up, sustained virologic response was achieved in 23 of 45 (51.1%) patients from group A and 21 of 65 patients (32.3%) from group B (P =0.075). CONCLUSION: Pegylated interferon alpha-2b/ribavirin treatment achieved a significantly higher compliance rate than interferon alpha-2b/ribavirin in MM patients with chronic HCV infection. After 24 weeks of follow-up, response rates were similar for patients who were compliant to treatment for both groups.