Pilot Outreach Program in Remedis-The Promising Step toward HCV Elimination among People Who Inject Drugs.

The global effort to eliminate HCV infection requires new approaches to accessing and testing the affected population in a setting with as low of a threshold as possible. The focus should be on socially marginalized people who inject drugs (PWIDs) and who are not willing or able to visit standard medical services. With this vision, we established an outreach service-a testing point in an ambulance in the park in front of the Main Railway Station of the capital city of Prague-to provide bloodborne disease testing and treatment. The service was available every week on Wednesday afternoon. Over the initial two years of our experience, 168 unique people were tested. Of them, 82 (49%) were diagnosed with chronic HCV infection and were eligible for treatment with antivirals. Of these, 24 (29%) initiated antiviral treatment over the study period, and 17 (71%) of these individuals achieved a documented sustained virological response. Offering medical services in PWIDs' neighborhoods helps overcome barriers and increase the chances that they will become patients and begin HCV treatment. The described outcomes appear promising for reaching the vision of linkage to the care of such a hard-to-reach population and can serve as a feasible model of care for further expansion.

Efficacy and safety of peginterferon α-2a (40 KD) plus ribavirin in treatment-naive chronic hepatitis C patients in Central and Eastern Europe.

OBJECTIVE: Assess the safety and efficacy of 24 or 48 weeks of treatment with peginterferon α-2a (40 KD) plus ribavirin in treatment-naive patients with chronic hepatitis C. METHODS: All patients in this open-label multinational study were assigned at the investigator's discretion to receive peginterferon α-2a (40 KD) 180 µg/week plus ribavirin (800 mg/day) for a total of 24 weeks or peginterferon α-2a (40 KD) 180 µg/week plus ribavirin (1000/1200 mg/day) for a total of 48 weeks. Treatment success was defined as sustained virological response [sustained virological response (SVR); hepatitis C virus RNA less than 50 IU/ml after completion of untreated follow-up]. RESULTS: A total of 789 treatment-naive patients were enrolled, of whom 91% (138 of 152) of nongenotype 1 patients and 77% (490 of 637) of genotype 1 patients completed 24 and 48 weeks of treatment, respectively. The overall SVR rate was 58% (459 of 789), and was 70 and 55% in nongenotype 1 and genotype 1 patients, respectively. Age (per 10-year decrement) and baseline hepatitis C virus RNA level (≤ 400 000 vs. >4 00 000 IU/ml) were significantly associated with SVR by multiple logistic regression analysis. The safety profile of peginterferon α-2a (40 KD) plus ribavirin was similar to that reported in pivotal trials, with no new or unexpected safety signals. CONCLUSION: The combination of peginterferon α-2a (40 KD) plus ribavirin was well tolerated and produced an overall SVR rate of 58% in treatment-naive patients. This study confirms that SVR rates achieved in pivotal clinical trials in Western Europe and the USA can be achieved in routine clinical practice in Central and Eastern Europe.

Efficacy and safety of peginterferon α-2a (40 kD) plus ribavirin among patients with chronic hepatitis C and earlier treatment failure to interferon and ribavirin: an open-label study in central and Eastern Europe.

OBJECTIVE: To assess the safety and efficacy of 48 weeks of re-treatment with peginterferon α-2a (40 kD) plus ribavirin in previously treated hepatitis C virus (HCV) genotype 1 patients. METHODS: HCV genotype 1 patients previously treated with conventional interferon with or without ribavirin were assigned to 48 weeks of treatment with peginterferon α-2a (40 kD; 180 µg/week) plus ribavirin (recommended dose: 1000/1200 mg/day) in this open-label trial conducted in central and Eastern Europe. The primary efficacy endpoint was sustained virological response (SVR, HCV RNA <50 IU/ml) after 24 weeks of untreated follow-up. Early virological response (EVR) was defined as an undetectable HCV RNA or at least 2-log drop at week 12. RESULTS: A total of 154 of the 203 (76%) treatment-experienced genotype 1 patients completed the treatment. Overall, 113 patients (56%) achieved an EVR, 107 (53%) had an end-of-treatment response and 63 patients (31%) achieved an SVR [including 38% (40/105) of those with an earlier breakthrough or relapse and 24% (21/88) of those with earlier nonresponse]. Among patients with an EVR, 47% (53/113) achieved an SVR (positive predictive value=47%), compared with 3% (1/34) of patients without an EVR (negative predictive value=97.1%). Rates of SVR were higher in patients without cirrhosis (54/169, 32%), with a baseline viral load of 800 000 IU/ml or less (29/68, 43%) and younger than 40 years of age (36/77, 47%). CONCLUSION: The combination of peginterferon α-2a (40 kD) plus ribavirin produced an overall SVR rate of 31% in difficult-to-treat genotype 1 patients who had not responded to the previous treatment with conventional interferon plus ribavirin.

Albinterferon alfa-2b dosed every two or four weeks in interferon-naïve patients with genotype 1 chronic hepatitis C.

UNLABELLED: The efficacy and safety of albinterferon alfa-2b (alb-IFN), a novel recombinant protein consisting of interferon alfa-2b genetically fused to human albumin, was evaluated in a phase 2b, open-label study of patients with genotype 1, chronic hepatitis C. In all, 458 IFN-alfa treatment-naïve patients were randomized to 48-week treatment with peginterferon alfa (PEG-IFNalpha)-2a 180 microg one time per week (qwk), or alb-IFN 900 or 1,200 microg once every two weeks (q2wk), or 1,200 microg once every four weeks (q4wk), administered subcutaneously, plus weight-based oral ribavirin 1,000 or 1,200 mg/day. Hepatitis C virus RNA was measured by real-time polymerase chain reaction (limit of detection: 10 IU/mL). The primary efficacy endpoint was sustained virologic response (hepatitis C virus RNA <10 IU/mL 24 weeks after the end of treatment). By intention-to-treat analysis, sustained virologic response rates were 58.5% (69/118) with alb-IFN 900 microg q2wk, 55.5% (61/110) with 1,200 microg q2wk, and 50.9% (59/116) with 1,200 microg q4wk, and 57.9% (66/114) with PEG-IFNalpha-2a (P = 0.64 for overall test). Discontinuation rates due to adverse events were 9.3% with alb-IFN 900 microg q2wk, 18.2% with 1,200 microg q2wk and 12.1% with 1,200 microg q4wk, and 6.1% with PEG-IFNalpha-2a (P = 0.04). Hematologic reductions were lowest in the q4wk group and comparable across other groups. At week 12, mean treatment-associated missed workdays were significantly lower with alb-IFN 900 mug q2wk versus PEG-IFNalpha-2a (1.1 versus 4.3 days; P = 0.006). CONCLUSION: Alb-IFN administered q2wk or q4wk may offer comparable efficacy, with an improved dosing schedule, compared with PEG-IFNalpha-2a.

Hepatitis C virus infection among injecting drug users in the Czech Republic -- prevalence and associated factors.

AIM: To determine the prevalence of, and factors associated with, hepatitis C virus (HCV) infection in the population of Czech injecting drug users (IDUs). DESIGN: Multicentric cross-sectional study. SETTING: A convenience sample of injecting drug users was recruited using the snowball sampling method. PARTICIPANTS: Sample of 760 IDUs from 9 different Czech regions. MEASUREMENT: We used one-drop instant blood tests to determine the anti-HCV antibodies status; a structured questionnaire was completed during the interview with the researcher. We calculated the ratio of positive findings and performed univariate analyses of correlations between predictors and independent variables. Finally, we created a logistic regression model that controlled for age, region of residence, reported sharing of injection paraphernalia, and length of injection drug use and for the interaction between length of injection use and imprisonment in order to assess the predictive value of imprisonment in an individual's history. FINDINGS: 226 participants (29.74% of the tested sample) were found to be anti-HCV positive. After adjusting for the sensitivity of the test, the 'true proportion' was 34.97% (95% CI: 31.56-38.35). Many correlated independent variables were found in the univariate analyses. In our logistic regression model, we have found that imprisonment increases the odds of being anti-HCV positive by a factor of 4.3. CONCLUSION: Anti-HCV seroprevalence remains relatively low in the Czech IDUs population compared to similar populations in the developed countries. Regional differences exist in anti-HCV prevalence within the Czech Republic. The strong association of anti-HCV prevalence with imprisonment history when controlled for other potentially clinically important factors suggests the need for more effective preventive measures in Czech prisons.

Hepatitis C virus (HCV) 5'NC sequence variants and their association with hepatitis C risk groups.

BACKGROUND: Genotype distribution of hepatitis C virus (HCV) is relatively uniform in Prague, Czech Republic. Unlike the other developed countries where HCV genotype 3 is increasingly associated with injection drug users (IDU), subtype 1b remains the most prevalent HCV subtype in Prague, regardless of risk factors. OBJECTIVE: We wished to determine if subtype 1b strains could be further differentiated by comparing the conserved 5'NC sequences of the strains infecting IDU and non-IDU populations. STUDY DESIGN: All prospectively collected serum samples that were HCV RNA positive were genotyped according to the 5'NC and NS5b regions. All 5'NC sequences were further analyzed for new mutations and these data were compared to patient epidemiologic information. RESULTS: We found eight 5'NC sequence variants among 96 specimens tested. Further analysis of subtype 1b strains showed that a variant with a nucleotide insertion at -138 positions was found only among non-IDU subjects, while the variant with T-->C substitution at -94 was found only among the IDUs. CONCLUSIONS: These observations suggest that the current HCV transmission between the IDU and non-IDU populations is uncommon, and may reflect the beginning of divergence of HCV genotypes in the IDU population in Prague.

Genotypic distribution of hepatitis B virus in the Czech Republic: a possible association with modes of transmission and clinical outcome.

OBJECTIVE: The relationship between hepatitis B virus (HBV) genotype with disease or treatment outcome is beginning to be characterized. However, the link between genotype and disease transmission route has not been closely examined. We addressed this question in high-risk populations in Prague, Czech Republic. DESIGN: Patients with HBV infection were consecutively recruited into the study at an outpatient clinic between June 2000 and March 2001. Their serum samples were analysed for HBV S gene segments by polymerase chain reaction (PCR) test. The amplified product sequences were compared to those of known HBV genotypes. Patients were evaluated for other virus co-infections, and parenteral and sexual exposure histories. RESULTS: Of 57 consecutively recruited patients with evidence of HBV infection, 45 (79%) had PCR-detectable S gene sequences. Only genotypes A (n = 33; 73%) and D (n = 12; 27%) were found. There was no difference in the development of chronic infection between the two genotypes. Of nine patients co-infected with TTV, all were infected with HBV genotype A. There was a trend towards an association between number of lifetime sex partners and genotype A but not genotype D. CONCLUSIONS: In Prague, the number of HBV genotypes appears to be limited compared to other northern European countries, suggesting that the virus has recently spread in the high-risk populations. While a large proportion of HBV infections occur in intravenous drug users, a subset of HBV genotype A may be transmitted by sexual contact. An HBV subtype may influence modes of transmission of HBV.