Effectiveness of 12 week ledipasvir/sofosbuvir and predictors of treatment failure in patients with hepatitis C.

OBJECTIVE: The efficacy of ledipasvir/sofosbuvir (LDV/SOF) have been demonstrated in randomized controlled trials, however,there is an unmet need for real-world effectiveness data. It is important to gather data regarding potential predictors of treatment failure with (LDV/SOF). Predictors of sustained virologic response (SVR) to all-oral HCV regimens can inform nuanced treatment decisions. The objectives of this study were to evaluate the effectiveness of LDV/SOF, SVR12 as main endpoint and SVR24 as second endpoint, and identify predictors of treatment failure. METHODS: Retrospective and observational study carried out from April 2015 to January 2016. Inclusion criteria: patients with HCV infection treated with LDV/SOF for 12 weeks during study period. The patients that were treated during 24 weeks were excluded as well as those treated with peg-interferon. Binary logistic regression was used to predict what variable was associated with treatment failure. RESULTS: A total of 122 patients were analyzed achieving SVR12 91.80% (112/122) of them. The patients with HCV genotype (GT) 1a or GT1b or GT4 achieved SVR12. Only one pre-treated non-cirrhotic HCV GT1 patients relapsed to treatment. The lowest SVR12 were obtained for GT3, 43.75%, (7/16). Everybody that got SVR12 achieved SVR24. None of the variables analyzed significantly influenced the SVR12, except GT (p=0.001). Almost all the relapses occurred in GT3. CONCLUSIONS: LDV/SOF combination has been very effective to treat GT1 and GT4 infected patients, however, has constituted a suboptimal therapeutic option for those patients infected with GT3, regardless of the rest of the variables analyzed.

Direct-acting antiviral agents in patients with hepatitis C genotype 1-4 infections in a tertiary hospital.

OBJECTIVE: Hepatitis C virus (HCV) infection is a major cause of chronic liver disease. Six different genotypes (GT) of HCV (genotypes 1-6) have been identified. The genotype is clinically relevant since the majority of current direct antiviral agents (DAA´s) do not have pangenotypic efficacy. The purpose of this study was to describe the clinical characteristics of real world patients and evaluate the effectiveness of different treatment regimens. METHODS: Retrospective and observational study carried out in a third level hospital. Study period: January 2015-January 2016. Inclusion criteria: HCV patients of any genotype treated with either DAAs ± rivabirin (RBV) or DAAs + RBV + pegilated interferon (Peg-IFN) regimens for 12 weeks. Exclusion criteria: patients without adequate clinical or analytical information available for further analysis. Patients treated for 24 weeks were excluded. The main endpoint was sustained virologic response 12 weeks after the end of treatment (SVR12), and secondary endpoint was SVR24. RESULTS: A total of 515 patients were included (aged 55.52±8.97 years). GT1: patients treated with simeprevir + sofosbuvir (SIM + SOF), ledipavir (LDV)/SOF and paritaprevir/ritonavir/ombitasvir + dasabuvir (PTV/r/OBV + DSV) ± RBV had a SVR12 of 93.59% (190/203), 98.82% (N=84/85), 94.28% (66/70), respectively. Regarding daclatasvir (DCV) + SOF and SIM + DCV, everybody (19/19) and 87.5% (7/8) got SVR12, respectively. GT2: 71.42% (N=10/14) of patients achieved SVR12, concretely, SOF + RBV had a SVR12 75% (N=6/8). GT3: 43.75% (N=7/16), 90% (N=9/10) and 95% (N=19/20) of patients treated with LDV/SOF, LDV/SOF + RBV and SOF + DCV obtained SVR12, respectively. GT4: patients treated with LDV/SOF, SIM + SOF and PTV/r/OBV ± RBV had a SVR12 rate of 100% (21/21), 91.67% (22/24) and 92% (23/25), respectively. All patients that got SVR12 achieved SVR24. CONCLUSIONS: Our study confirmed the efficacy data reported in clinical trials in a cohort of patients with GT1-4 and a wide range of basal characteristics.

Interferon-free treatments in patients with hepatitis C genotype 3 infection in a tertiary hospital.

OBJECTIVE: Hepatitis C virus genotype 3 represents a unique entity within HCV treatment and multiple studies have documented that HCV genotype 3 infection is associated with more rapid disease progression than other genotypes, resulting in increased risk of cirrhosis, hepatocellular carcinoma, and all-cause mortality. In the current study, we further evaluated the real-world effectiveness of 12 weeks of ledipasvir/sofosbuvir ± ribavirin (LDV/SOF ± RBV) and sofosbuvir + daclatasvir (SOF + DCV) for treatment-naive or treatment-experienced patients infected with HCV genotype 3, with or without cirrhosis. METHODS: Retrospective and observational study carried out in a third level hospital. Study period: April 2015 to January 2016. Inclusion criteria: Patients with HCV genotype-3 infection treated either with LDV/SOF ± RBV or with SOF + DCV during study period treated for 12 weeks. The patients that were treated during 24 weeks were excluded and those treated with peg-interferon. The main endpoint measured was the sustained virologic response (SVR) at 12 weeks (SVR12) and the secondary endpoint was SVR at 24 weeks (SVR24). RESULTS: During the study period, 603 patients were treated in our hospital: 71 with genotype 3. We included 46 patients who were treated with LDV/SOF ± RBV or SOF + DCV for 12 weeks. A 43.75% (7/16) of all patients treated with LDV/SOF achieved SVR12, 90% (9/10) of the patients treated with LDV/SOF+RBV achieved SVR12 and 95% (19/20) of the patients treated with SOF+DCV achieved SVR12. There was statistically significant difference (p=0.001) between LDV/SOF respect to SOF+DCV and between LDV/SOF with regard to LDV/SOF +RBV (p=0.018) used to treat HCV genotype 3 infection. CONCLUSIONS: In conclusion, in our cohort of patients, the combination of SOF + DCV followed by LDV/SOF + RBV 12 weeks were the most effective in patients with HCV genotype 3 and with cirrhosis (SVR12 90% and 80%, respectively) and in those without cirrhosis (SVR12 100% in both combinations). All patients who achieved SVR12 also achieved SVR24, regardless of the regimen received.

[Darunavir/cobicistat monotherapy. Experience in a tertiary hospital]. / Monoterapia con darunavir/cobicistat. Experiencia en un hospital de tercer nivel.

OBJECTIVE: Ritonavir-boosted protease inhibitor (IP/r) monotherapy: darunavir/ritonavir (DRV/r) or lopinavir/ritonavir (LPV/r) monotherapy is only provided in the major treatment guidelines in pretreated patients to prevent toxicity associated with nucleoside/nucleotide reverse transcriptase inhibitor (NRTI), reduce costs and simplify antiretroviral treatment. To start IP/r monotherapy, according to GESIDA guidelines 2016, patients need to meet the following criteria: absence of chronic hepatitis B, plasma viral load <50 copies/ mL for at least 6 months and absence of protease inhibitors mutations or previous virologic failures to IP/r. Currently, there are no studies that evaluate the efficacy and safety of darunavir/cobicistat (DRV/COBI) monotherapy. METHODS: This prospective study analyzed pretreated HIV patients with DRV/r monotherapy that were switched to DRV/COBI monotherapy. The aim of the study is to describe the effectiveness and safety of the DRV/COBI monotherapy. RESULTS: Seventy-eight patients were evaluated. Patients had a median of 31.29 months of DRV/r monotherapy before DRV/COBI monotherapy. Nine of the 78 patients developed "blips" (plasma viral load: 50-200 copies/ml) and four patients had plasma viral load ≥200 copies/mL. An 83.3% (65/78) of the patients remained with undetectable plasma viral load. As for safety, there were no significant differences in lipid profile, liver function (transaminases) and renal function between DRV/r and DRV/COBI monotherapy. CONCLUSIONS: DRV/COBI monotherapy seems to be effective and safe (lipid profile, liver and kidney function). However, it will be necessary to design specific studies comparing DRV/r vs DRV/COBI monotherapy to confirm these results.