Background Tocilizumab blocks pro-inflammatory activity of interleukin-6 (IL-6), involved in pathogenesis of pneumonia the most frequent cause of death in COVID-19 patients. Methods A multicenter, single-arm, hypothesis-driven trial was planned, according to a phase 2 design, to study the effect of tocilizumab on lethality rates at 14 and 30 days (co-primary endpoints, a priori expected rates being 20 and 35%, respectively). A further prospective cohort of patients, consecutively enrolled after the first cohort was accomplished, was used as a secondary validation dataset. The two cohorts were evaluated jointly in an exploratory multivariable logistic regression model to assess prognostic variables on survival. Results In the primary intention-to-treat (ITT) phase 2 population, 180/301 (59.8%) subjects received tocilizumab, and 67 deaths were observed overall. Lethality rates were equal to 18.4% (97.5% CI: 13.6–24.0, P = 0.52) and 22.4% (97.5% CI: 17.2–28.3, P < 0.001) at 14 and 30 days, respectively. Lethality rates were lower in the validation dataset, that included 920 patients. No signal of specific drug toxicity was reported. In the exploratory multivariable logistic regression analysis, older age and lower PaO2/FiO2 ratio negatively affected survival, while the concurrent use of steroids was associated with greater survival. A statistically significant interaction was found between tocilizumab and respiratory support, suggesting that tocilizumab might be more effective in patients not requiring mechanical respiratory support at baseline. Conclusions Tocilizumab reduced lethality rate at 30 days compared with null hypothesis, without significant toxicity. Possibly, this effect could be limited to patients not requiring mechanical respiratory support at baseline. Registration EudraCT (2020-001110-38); clinicaltrials.gov (NCT04317092).

This nonrandomized study compared the virologic and immunologic responses to potent regimens containing either efavirenz or nevirapine after considering potential systematic differences between patients receiving these drugs. Virologic failure was defined as the first of 2 consecutive measurements of virus load >500 human immunodeficiency virus RNA copies/mL. Of the 694 patients included in the analysis, 460 (66.3%) started nevirapine and 234 (33.7%) started efavirenz. The adjusted relative hazard of virologic failure for patients who started nevirapine, compared with those who started efavirenz, was 2.08 (95% confidence interval, 1.37-3.15; P=.0006). In addition, patients receiving efavirenz tended to recover 5 CD4 cells/microL more per quarter (P=.05). Although comparisons of drug efficacy in nonrandomized studies should be viewed with caution, no results from randomized controlled comparisons of these drugs are thought to be available. The findings of this study are in agreement with those of other observational studies.

Background and aims:It is paramount to identify predictors of treatment failure with direct antiviral agents in 'field-practice' patients, including people who inject drugs (PWID). Data on the efficacy of glecaprevir/pibrentasvir (GLE/PIB) in a field-practice scenario are scant. The multicentre MISTRAL study enrolled 1177 patients, including PWID, to assess real-life efficacy and safety of GLE/PIB and to identify the predictive factors for this treatment. Methods:This was a prospective, longitudinal study. The outcome variable was the rate of sustained virological response (SVR) at week 12.Results: A total of 123 patients (10%) were infected from hepatitis C virus (HCV) 3.METAVIR fibrosis score was F4 in 104 subjects (9%); 118 patients (10%) were PWID.Overall, 1163/1177 (99%) patients achieved SVR. The baseline clinical factors discriminating between treatment success and treatment failure were age at treatment (P = 0.031) and creatinine level (P = 0.034). SVR rates were not influenced by gender, substance abuse, previous treatment, treatment duration, fibrosis or chronic kidney disease stage. Compared with non-substance users, the 118 PWID exhibited a significantly different genotype pattern distribution (χ 2 < 0.001). A total of 40/118 (33.9%) of substance users were HCV3 compared to 83/1056 (7.9%) non-substance users.Only 6 patients (0.5%) reported a serious adverse event. Conclusions:The MISTRAL study provides evidence of GLE/PIB efficacy in a fieldpractice scenario in a highly epidemic HCV area in southern Italy; it unveiled significant differences in genotype distribution among the most underserved and difficult-to-treat patient subgroups including PWID. K E Y W O R D S cirrhosis, direct-acting antiviral, efficacy, HCV genotype, substance abuse Keypoints • The MISTRAL study shows that glecaprevir/pibrentasvir is effective for the treatment of hepatitis C virus in a field-practice scenario in a highly epidemic area in southern Italy. Handling editor: Alessio Aghemo S U PP O RTI N G I N FO R M ATI O N Additional supporting information may be found online in the Supporting Information section at the end of the article. How to cite this article: Persico M, Aglitti A, Milella M, et al. Real-life glecaprevir/pibrentasvir in a large cohort of patients with hepatitis C virus infection: The MISTRAL study. Liver Int.

The pool of HCV genotype 1 patients likely to be cured by peg-interferon and ribavirin remains to be quantified

Our findings support the use of DAAs in patients with advanced cirrhosis (stages 3-5) who are at greatest risk and have the most to gain from therapy.