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INTRODUCTION: We assessed the performance of direct-acting antivirals (DAAs) in hepatitis C virus (HCV)-infected people who use drugs (PWUDs) in terms of sustained virological response (SVR) and adherence rates in comparison to a location-matched cohort of non-PWUD HCV patients. METHODS: All consecutive HCV RNA-positive PWUDs were enrolled between 2015 and 2019. All subjects underwent DAA treatment according to international guidelines and then followed, at least, up to 12 weeks after the end of treatment (SVR12). The SVR and adherence to treatment was compared with that of non-PWUD HCV patients observed at hepatological units of the CLEO platform. Intention-to-treat analysis was performed. RESULTS: A total of 1,786 PWUDs who were followed up were available for assessment. Most PWUDs (85.4%) were managed inside the specialized outpatient addiction clinics (SerDs). The overall SVR rate was 95.4%. The SerDs group achieved an SVR rate of 96.2%compared with 91.6% of the non-SerDs group (P < 0.001). Comparison with the non-SerDs group and the control HCV group showed a significant difference in the dropout rate (0.6% in the SerDs group versus 2.8% in the non-SerDs group and 1.2% in the control group; P < 0.001). At multivariate analysis, factors independently associated with SVR were use of the most recent regimens (elbasvir/grazoprevir, glecaprevir/pibrentasvir, and sofosbuvir/velpatasvir; odds ratio: 3.126; P = 0.000) and belonging to the SerDs group (odds ratio: 2.356; P = 0.002). DISCUSSION: The performance of DAAs in PWUD is excellent, if 2 conditions are met: (i) that the latest generation drugs are used and (ii) that the patients are managed within the SerDs. [ABSTRACT FROM AUTHOR]

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 (χ2 < 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 field‐practice 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. [ABSTRACT FROM AUTHOR]

Background & Aims In patients with chronic HCV-1 infection, recent evidences indicate that determination of a dinucleotide polymorphism (ss469415590, ΔG/ TT) of a new gene, designated IFN λ-4, might be more accurate than the 12979860 CC type of the IL28B locus in predicting sustained virological response ( SVR) following peg-interferon and ribavirin. In addition, combined genotyping of different SNPs of the IL28B locus was shown to help dissect patients most prone to SVR among those with rs12979860 CT. We examined whether single or combined genotyping of two IL28B SNPs, rs12979860 and rs8099917, and ss469415590 variation might improve the prediction of SVR. Results In the study cohort of 539 patients, 38% had SVR. The SNPs 12979860 CC, rs8099917 TT, and rs469415590 TT/ TT correlated significantly with SVR (68%, 50%, and 67%). Carriers of either the triplotype rs12979860 CC_ss469415590 TT/ TT_rs8099917 TT or the diplotype rs12979860 CC_ss469415590 TT/ TT had the highest SVR rate (72%). In carriers of the rs12979860 T allele, neither the rs8099917 nor the ss469415590 improved the response prediction. After pooling this finding with data from previous studies, in rs12979860 T heterozygous individuals the co-presence of the rs8099917 TT SNP was associated with improved response prediction. Conclusion In HCV-1 patients, the rs12979860 polymorphism appeared as the hit SNP better predicting response following peg-interferon and ribavirin treatment. Additional ss469415590 or rs8099917 genotyping had no added benefit for response prediction. In the subset of carriers of the rs12979860 T allele, genotyping of the rs8099917 SNP was unhelpful in the present investigation, but may inform clinical prediction of treatment response when our data were pooled with previous investigations. [ABSTRACT FROM AUTHOR]

Background & Aims: The pool of HCV genotype 1 patients likely to be cured by peg-interferon and ribavirin remains to be quantified. Methods: In 1045 patients treated with peg-interferon and ribavirin, two therapeutic strategies were confronted: the first one evaluated only baseline variables associated with sustained virological response (SVR), and the second one included the rapid virologic response (RVR) in addition to baseline predictors. An 80% SVR rate was the threshold to retain a strategy as clinically relevant. Results: Overall, 414 patients (39.6%) attained SVR. In the first strategy, the hierarchy of features independently associated with SVR was IL28B CC genotype (OR 5.082; CI 3.637–7.101), low (<400,000IU) viremia (OR 2.907; CI 2.111–4.004), F0–F2 fibrosis (OR 1.631; CI 1.122–2.372) and type 2 diabetes (OR 0.528; CI 0.286–0.972). In the alternative strategy, SVR was associated with RVR (OR 6.273; CI 4.274–9.208), IL28B CC genotype (OR 3.306; CI 2.301–4.751), low viremia (OR 2.175; CI 1.542–3.070), and F0–F2 fibrosis (OR 1.506; CI 1.012–2.242). Combining the favorable baseline variables, the rates of SVR ranged from 42.4% to 83.3%, but only 66 patients (6.3%, overall) with all predictors could be anticipated to reach the >80% SVR threshold. Only 26.6% of no-RVR patients attained SVR. Among the 255 RVR patients, the likelihood of SVR was 61.8% in those with unfavorable predictors, 80% in the presence of a single predictor, and 100% when both predictors were present. By using this model, 200 patients (19.1%) were predicted to have an 80% chance of being cured with dual therapy. Conclusions: A consistent subset of naïve HCV-1 patients, identified by some baseline characteristics and RVR, may benefit from dual treatment with peg-interferon and ribavirin. [Copyright &y& Elsevier]

Background: Metabolic syndrome (MS) represents a cluster of cardiovascular risk factors that has become a serious problem for HIV-1-infected patients. It has been proposed that disturbance of phosphate metabolism may represent a key feature of MS. Thus, we undertook the present study to investigate the relationship between phosphate levels and the presence of the characteristics of MS. Methods: One hundred and twenty-one HIV-1-infected patients were consecutively enrolled in a prospective, cross-sectional, single-centre study. Kidney tubular function was examined using tubular resorption of phosphate and normalized renal threshold phosphate concentration. Results: Univariate analysis showed that serum phosphate levels correlated negatively with systolic and diastolic blood pressure, glucose values, waist circumference, insulin, and triglycerides. Moreover, there was a positive relationship between phosphate and high-density lipoprotein (HDL) cholesterol. Multivariate analysis showed that insulin levels were correlated with serum phosphate concentration ( r == − 0.24, p == 0.01). Conclusions: Our data show that HIV-1-infected patients with MS have lower phosphate levels. [ABSTRACT FROM AUTHOR]

Examines the frequency of first therapy interruption (TI) of highly active antiretroviral therapy (HAART) in HIV clinical practice. Identification of the factors associated with TI and therapy resumption; Risk of developing clinical events during TI and during continuous therapy; Implications for the management of HAART.