SummaryBackgroundSince the 1918 influenza pandemic, non-randomised studies and small clinical trials have suggested that convalescent plasma or anti-influenza hyperimmune intravenous immunoglobulin (hIVIG) might have clinical benefit for patients with influenza infection, but definitive data do not exist. We aimed to evaluate the safety and efficacy of hIVIG in a randomised controlled trial.MethodsThis randomised, double-blind, placebo-controlled trial was planned for 45 hospitals in Argentina, Australia, Denmark, Greece, Mexico, Spain, Thailand, UK, and the USA over five influenza seasons from 2013–14 to 2017–18. Adults (≥18 years of age) were admitted for hospital treatment with laboratory-confirmed influenza A or B infection and were randomly assigned (1:1) to receive standard care plus either a single 500-mL infusion of high-titre hIVIG (0·25 g/kg bodyweight, 24·75 g maximum; hIVIG group) or saline placebo (placebo group). Eligible patients had a National Early Warning score of 2 points or greater at the time of screening and their symptoms began no more than 7 days before randomisation. Pregnant and breastfeeding women were excluded, as well as any patients for whom the treatment would present a health risk. Separate randomisation schedules were generated for each participating clinical site using permuted block randomisation. Treatment assignments were obtained using a web-based application by the site pharmacist who then masked the solution for infusion. Patients and investigators were masked to study treatment. The primary endpoint was a six-category ordinal outcome of clinical status at day 7, ranging in severity from death to resumption of normal activities after discharge. The choice of day 7 was based on haemagglutination inhibition titres from a pilot study. It was analysed with a proportional odds model, using all six categories to estimate a common odds ratio (OR). An OR greater than 1 indicated that, for a given category, patients in the hIVIG group were more likely to be in a better category than those in the placebo group. Prespecified primary analyses for safety and efficacy were based on patients who received an infusion and for whom eligibility could be confirmed. This trial is registered with ClinicalTrials.gov, NCT02287467.Findings313 patients were enrolled in 34 sites between Dec 11, 2014, and May 28, 2018. We also used data from 16 patients enrolled at seven of the 34 sites during the pilot study between Jan 15, 2014, and April 10, 2014. 168 patients were randomly assigned to the hIVIG group and 161 to the placebo group. 21 patients were excluded (12 from the hIVIG group and 9 from the placebo group) because they did not receive an infusion or their eligibility could not be confirmed. Thus, 308 were included in the primary analysis. hIVIG treatment produced a robust rise in haemagglutination inhibition titres against influenza A and smaller rises in influenza B titres. Based on the proportional odds model, the OR on day 7 was 1·25 (95% CI 0·79–1·97; p=0·33). In subgroup analyses for the pr...
Aims To project the impact of scaling up oral antiviral 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 programs to achieve specific targets and to examine whether hepatitis C viruse (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 reinfection following treatment. Setting/Participants The population of 8,300 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 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%–90% in 2030, compared with 2016. CHC prevalence would reduce 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 (HCV) treatment and harm reduction interventions could achieve major reductions in HCV incidence and prevalence among people who inject drugs (PWID) 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 PWID per year combined with moderate increases in harm reduction coverage.
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.
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.
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. Keywords Direct-acting antivirals, hepatitis C virus infection, people who inject drugs, sustained virological response, lost to follow up
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