Hepatitis C (HCV) therapy for HCV mono-infected and HIV-HCV co-infected individuals living in Nepal.

BACKGROUND: Despite direct-acting antivirals (DAA), aims to "eradicate" viral hepatitis by 2030 remain unlikely. In Nepal, an expert consortium was established to treat HCV through Nepal earthquakes aftermath offering a model for HCV treatment expansion in a resource-poor setting. METHODOLOGY/PRINCIPAL FINDINGS: In 2015, we established a network of hepatologists, laboratory experts, and community-based leaders at 6 Opioid Substitution Treatment (OST) sites from 4 cities in Nepal screening 838 patients for a treatment cohort of 600 individuals with HCV infection and past or current drug use. During phase 1, patients were treated with interferon-based regimens (n = 46). During phase 2, 135 patients with optimal predictors (HIV controlled, without cirrhosis, low baseline HCV viral load) were treated with DAA-based regimens. During phase 3, IFN-free DAA treatment was expanded, regardless of HCV disease severity, HIV viremia or drug use. Sustained virologic response (SVR) was assessed at 12 weeks. Median age was 37 years and 95.5% were males. HCV genotype was 3 (53.2%) or 1a (40.7%) and 32% had cirrhosis; 42.5% were HIV-HCV coinfected. The intention-to-treat (ITT) SVR rates in phase 2 and 3 were 97% and 81%, respectively. The overall per-protocol and ITT SVR rates were 97% and 85%, respectively. By multivariable analysis, treatment at the Kathmandu site was protective and substance use, treatment during phase 3 were associated with failure to achieve SVR. CONCLUSIONS/SIGNIFICANCE: Very high SVR rates may be achieved in a difficult-to-treat, low-income population whatever the patient's profile and disease severity. The excellent treatment outcomes observed in this real-life community study should prompt further HCV treatment initiatives in Nepal.

Outcomes of Patients in Long-Term Opioid Maintenance Treatment.

BACKGROUND: Despite the importance of duration of opioid maintenance treatment (OMT), only few studies have reported outcomes of long-term OMT. OBJECTIVES: To describe outcomes of long-term (> 5 years) OMT patients with respect to substance use, physical and mental health, and socioeconomic characteristics. METHODS: Patients (n = 160) were recruited from 15 OMT offices in different regions of Germany. Data were collected using a structured interview at baseline, and clinical recordings, including urine drug screenings, during 12 monhts follow-up. RESULTS: Patients had a mean age of 44 years. During follow-up, 23% of patients showed indications of an alcohol problem. Cannabis was used by 56%, often frequently. Heroin was used by 28%, mostly infrequently. Three quarters of patients either had a non-substance related mental disorder (48.1%, most frequently affective and anxiety disorders) or somatic diagnosis (61.3%, frequently hepatitis C, HIV, or cardiovascular diseases), or both. Unemployment rate was 43.1% at baseline (27% for patients without comorbidity) and remained generally stable during follow-up. No arrests or incarcerations were recorded. During follow-up, 2.5% of patients prematurely terminated OMT, 2.5% regularly completed OMT. CONCLUSIONS: The sample as a whole was characterized by stable living conditions, high unemployment, low illicit opiate use, and a high retention rate. Continuation of OMT could enable further treatment of comorbidity and prevent resumption of a drug-dominated lifestyle. But it may well be asked how within the context of OMT further improvements can be achieved, especially with regard to further decrease of alcohol use and the treatment of depression.

Psychoeducation improves hepatitis C virus treatment during opioid substitution therapy: a controlled, prospective multicenter trial.

BACKGROUND: People who inject drugs (PWID) have a high prevalence of hepatitis C virus (HCV) infection. However, PWID are considered "difficult to treat," requiring a specifically adapted treatment setting, including psychosocial support. METHODS: In this prospective, German trial, the impact of psychoeducation (PE) on retention and sustained virologic response (SVR) during HCV therapy among PWID was evaluated. We included 198 patients in opiate substitution therapy, who fulfilled indications for antiviral treatment. All patients received pegylated interferon alfa-2a and ribavirin therapy. Patients in the intervention group (n = 82) received manualized PE sessions. RESULTS: In patients with HCV genotype 1 or 4 (GT 1/4), PE was associated with increased treatment completion (76% vs 55%, P = .038), whereas PE had no such effect among GT 2/3 patients, who showed fewer dropouts and higher SVR rates. Among GT 1/4 patients, a minimum of 5 PE sessions was associated with increased SVR (71% vs 48%, P = .037). Multivariate regression analyses confirmed the impact of PE in GT 1/4 and revealed further predictors for retention and SVR, such as preexisting mental distress and adverse events. CONCLUSIONS: In patients with a higher risk of dropout due to GT 1/4 or mental distress, PE was shown to improve retention and SVR. PE is an effective supportive intervention for HCV therapy among PWID.

Psychopathological changes and quality of life in hepatitis C virus-infected, opioid-dependent patients during maintenance therapy.

AIMS: To examine among maintenance patients (methadone or buprenorphine) with and without hepatitis C virus (HCV) infection (i) the frequency of psychopathological symptoms at baseline and 1-year follow-up; (ii) the association between antiviral interferon (IFN) treatment and psychopathological symptoms; and (iii) to explore whether IFN therapy has an effect on 1-year outcome of maintenance treatment. DESIGN: Naturalistic prospective longitudinal cohort design. SETTING: A total of 223 substitution centres in Germany. PARTICIPANTS: A nationally representative sample of 2414 maintenance patients, namely 800 without and 1614 with HCV infection, of whom 122 received IFN therapy. MEASURES: HCV infection (HCV+/HCV-), IFN (IFN+/IFN-) treatment status and clinical measures. Diagnostic status and severity (rated by clinician), psychopathology (BSI--Brief Symptom Inventory) and quality of life (EQ-5D--EuroQol Group questionnaire). FINDINGS: HCV+ patients revealed indications for a moderately increased psychopathological burden and poorer quality of life at baseline and follow-up compared to HCV- patients. HCV+ patients showed a marked deterioration over time only in the BSI subscale somatization (P = 0.002), and the frequency of sleep disorders almost doubled over time (12.8% at baseline; 24.1% at follow-up; P < 0.01). IFN treatment, received by 10% of HCV+ patients, did not impair efficacy or tolerability of maintenance therapy and was associated overall with neither increased psychopathological burden nor reduced quality of life. CONCLUSIONS: Findings suggest no increased risk among HCV+ patients on maintenance therapy for depressive or other psychopathological syndromes. In our patient sample, IFN treatment was not associated with increased psychopathological burden, reduced quality of life or poorer tolerability and efficacy of maintenance treatment.

Feasibility and outcome of substitution treatment of heroin-dependent patients in specialized substitution centers and primary care facilities in Germany: a naturalistic study in 2694 patients.

BACKGROUND: In many countries, buprenorphine and methadone are licensed for the maintenance treatment (MT) of opioid dependence. Despite many short-term studies, little is known about the long-term (12-month) effects of these treatments in different settings, i.e. primary care-based (PMC) and specialized substitution centers (SSCs). OBJECTIVES: To describe over a period of 12 months: (1) mortality, retention and abstinence rates; (2) changes in concomitant drug use, somatic and mental health; and (3) to explore differences between different types of provider settings. METHODS: 12-Month prospective-longitudinal naturalistic study with four waves of assessment in a prevalence sample of N=2694 maintenance patients, recruited from a nationally representative sample of N=223 substitution physicians. RESULTS: The 12-month retention rate was 75%; the mortality rate 1.1%. 4.1% of patients became "abstinent" during follow-up. 7% were referred to drug-free addiction treatment. Concomitant drug use decreased and somatic health status improved. No significant improvements were observed for mental health and quality of life. When controlling for initial severity, small PMC settings revealed better retention, abstinence and concomitant drug use rates. CONCLUSION: The study underlines the overall 12-month effectiveness of various forms of agonist MT. Findings reveal relatively high retention rates, low mortality rates, and improvements in most 12-month outcome domains, except for mental health and quality of life. PMC settings appear to be a good additional option to improve access to MTs.

A new approach to preventing relapse in opiate addicts: a psychometric evaluation.

The present study investigated psychological aspects after different methods of withdrawal treatments in opiate addicts had been conducted. Two pharmacological strategies based on delivering an opioid agonist or antagonist were used for withdrawal in opiate addicts. After detoxification, the antagonist was delivered by a pellet implanted subcutaneously. Four days after the beginning of the treatment several psychological variables such as craving, anxiety, depression, and mood were assessed and compared with data from actively consuming opiate addicts and healthy controls. In addition, 6 and 12 weeks later the relapse rates were assessed. Compared with addicts detoxified and treated with Levomethadone as well as actively heroin consuming addicts, subjects treated with Naltrexone demonstrated significantly higher positive psychological outcome concerning all assessed variables and significantly lower relapse rates. Naltrexone implants prove prevention of relapse during the most vulnerable period after detoxification. Compared with Levomethadone withdrawal, they lead to a significantly better psychological condition in patients.

Buprenorphine and methadone in the treatment of opioid dependence: methods and design of the COBRA study.

Buprenorphine and methadone are the two established substitution drugs licensed in many countries for the treatment of opioid dependence. Little is known, however, about how these two drugs are applied and how they work in clinical practice. In this paper we present the aims, methods, design and sampling issues of a collaborative multi-stage epidemiological study (COBRA) to address these issues. Based on a nationally representative sample of substitution physicians, the study is designed as an observational, naturalistic study, consisting of three major parts. The first part was a national survey of substitution doctors (prestudy, n = 379 doctors). The second part was a cross-sectional study (n = 223 doctors), which consisted of a target-week assessment of 2,694 consecutive patients to determine (a) the severity and problem profiles and treatment targets; (b) the choice and dosage scheme of the substitution drug; (c) past and current interventions, including treatment of comorbid hepatitis C; and (d) cross-sectional differences between the two drugs with regard to comorbidity, clinical course, acceptance/compliance and social integration. The third part consists of a prospective-longitudinal cohort study of 48 methadone-treated and 48 buprenorphine-treated patients. The cohort is followed up over a period of 12 months to investigate whether course and outcome of the patients differ by type or treatment received in terms of clinical, psychosocial, pharmaco-economic and other related measures. The response rate among substitution doctors was 57.1%; that among eligible patients was 71.7%. Comparisons with the federal registers reveal that the final samples of doctors and patients may be considered nationally representative with regard to regional distribution, training, type of setting as well as the frequency of patients treated with buprenorphine or methadone. The COBRA study provides a unique comprehensive database, informing about the natural allocation and intervention processes in routine care and about the course and outcome of patients treated with buprenorphine or methadone.

Pilot study of interferon alpha high-dose induction therapy in combination with ribavirin for chronic hepatitis C in HIV-co-infected patients.

Twenty-three HIV/hepatitis C virus (HCV)-co-infected patients received dose-escalated IFN-alpha (5 MIU/day) induction therapy for 10 weeks, followed by 36 weeks of thrice-weekly IFN-alpha treatment (5 MIU), both in combinations with ribavirin. Sustained HCV clearance was observed in three patients. Nine patients discontinued the study aas a result of adverse reactions such as anaemia, pancreatitis and depression. In HIV/HCV-co-infected patients, the therapeutic benefit of high-dose IFN-alpha therefore seems to be limited by its poor tolerability.