Long-term efficacy and safety of atazanavir/ritonavir treatment in a real-life cohort of treatment-experienced patients with HIV type 1 infection

A total of 381 Suffolk, Ile de France, Poll Dorset, Santa Ines and crossbred sheeps was used to investigate variability, genetic relationship, and the efficiency of protein polymorphisms in racial characterization and parentage tests. The genetic characterization was done through electrophoresis and by isoelectric focusing. The investigated loci presented 64.7% of variability. Two new alleles of Hemoglobin, HbA1 and HbB1, were detected in Santa Ines, Suffolk and crossbred animals. The allele M of glucose phosphate isomerase is, probably, a genetic marker for the Suffolk breed. The values of Nei's Diversity for the leucine amino peptidase, nucleoside phosphorilase, hemoglobin and malic enzyme loci were higher than the others, indicating higherspecificity in sheep breed characterization. Fisher's test revealed that allelic frequencies were different among breeds (P < 0.01), with the exceptions of the alleles phosphogluconate dehydrogenase and Catalase loci (P > 0.05). This genic differentiation was confirmed by multivariate analysis, which dendrogram, constructed from the genetic distances, showed two main clusters: one clusters the wool and the other the hairy breeds. In the first cluster, two distinct subgroups are observed: one represented by the specialized breeds Poll Dorset and Ile de France, and the other represented by the Suffolk group, demonstrating the genetic relationships among breeds. The efficiency of these markers to exclud one of two possible sires was 76.7, 68.0, 61.3 and 84.8 % for the Poll Dorset, Ile de France, Suffolk and Santa Ines breeds, respectively. The inclusion of other markers will increase the efficiency to 100% and will allow greater precision in investigation of paternity

Daclatasvir plus sofosbuvir, with or without ribavirin, in real-world patients with HIV-HCV coinfection and advanced liver disease

Background: HIV-HCV-coinfected patients respond just as well to modern direct-acting antiviral HCV therapy as HCV-monoinfected patients. However, clinical data for all-oral HCV treatments are sparse in HIV-HCV-coinfected patients with an advanced stage of liver cirrhosis. Methods: A subanalysis of efficacy and safety for a daclatasvir (DCV) and sofosbuvir (SOF) regimen, with or without ribavirin (RBV), was undertaken in HIV-HCV-coinfected patients with advanced liver disease and no other treatment options enrolled into a European DCV compassionate use programme. Results: Fifty five HIV-HCV (mostly genotypes 1, 3, 4) coinfected patients were treated with DCV+SOF with (n=16) or without RBV (n=39), mostly for 24 weeks. Patients were predominantly (95%) cirrhotic (50% were Child-Pugh class B or C) and were receiving a wide range of antiretrovirals; 40% were injection drug users and 25% were receiving oral opioid substitution. Sustained virological response at post-treatment week 12 (SVR12) by modified intention-to-treat analysis (n=52) was 92% overall (95% CI 81.5, 97.9), and was similar with (94% [95% CI 69.8, 99.8]) or without RBV (92% [95% CI 77.5, 98.2]). Only one patient relapsed (Child-Pugh class B). The overall SVR12 rate after excluding non-virological failures (n=49) was 98% (95% CI 89.1, 99.9). Four patients discontinued treatment for adverse events and one died during treatment (not treatment-related). No patient lost opioid maintenance or required a change of antiretrovirals due to drug-drug interactions. Conclusions: DCV+SOF, with or without RBV, showed high SVR12 rates and was well tolerated in this real-world cohort of HIV-HCV-coinfected patients with very advanced liver diseas

Daclatasvir plus sofosbuvir, with or without ribavirin, achieved high sustained virological response rates in patients with HCV infection and advanced liver disease in a real-world cohort

Objective We assessed the effectiveness and safety of daclatasvir (DCV) plus sofosbuvir (SOF), with or without ribavirin (RBV), in a large real-world cohort, including patients with advanced liver disease. Design Adults with chronic HCV infection at high risk of decompensation or death within 12 months and with no available treatment options were treated in a European compassionate use programme. The recommended regimen was DCV 60 mg plus SOF 400 mg for 24 weeks; RBV addition or shorter duration was allowed at physicians' discretion. The primary endpoint was sustained virological response at post-treatment week 12 (SVR12). Results Of the 485 evaluable patients, 359 received DCV+SOF and 126 DCV+SOF+RBV. Most patients were men (66%), white (93%) and treatment-experienced (70%). The most frequent HCV genotypes were 1b (36%), 1a (33%) and 3 (21%), and 80% of patients had cirrhosis (42% Child–Pugh B/C; 46% Model for End-Stage Liver Disease score >10). SVR12 (modified intention-to-treat) was achieved by 91% of patients (419/460); 1 patient had virological breakthrough and 13 patients relapsed. Virological failure was not associated with treatment group (adjusted risk difference DCV+SOF minus DCV+SOF+RBV: 1.06%; 95% CI −2.22% to 4.35%). High SVR12 was observed regardless of HCV genotype or cirrhosis, liver transplant or HIV/HCV coinfection status. Twenty eight patients discontinued treatment due to adverse events (n=18) or death (n=10) and 18 died during follow-up. Deaths and most safety events were associated with advanced liver disease and not considered treatment related. Conclusions DCV+SOF with or without RBV achieved high SVR12 and was well tolerated in a diverse cohort of patients with severe liver disease. Trial registration number NCT0209966

RENACER study: Assessment of 12-month efficacy and safety of 168 certolizumab PEGol rheumatoid arthritis-treated patients from a Spanish multicenter national database

Objective: To assess effectiveness and safety of certolizumab PEGol (CZP) in rheumatoid arthritis (RA) patients after 12 months of treatment and to detect predictors of response.Methods: Observational longitudinal prospective study of RA patients from 35 sites in Spain. Variables (baseline, 3- and 12-month assessment): sociodemographics, previous Disease Modifying Anti-Rheumatic Drug (DMARD) and previous Biological Therapies (BT) use; TJC, SJC, ESR, CRP, DAS28, SDAI. Response variables: TJC, SJC, CRP, ESR, and steroids dose reductions, EULAR Moderate/Good Response, SDAI response and remission, DAS28 remission. Safety variables: discontinuation due to side-effects. Descriptive, comparative and Logistic regression analyses were performed.Results: We included 168 patients: 79.2% women, mean age 54.5 years (+/- 13.2 SD), mean disease duration 7.5 years (+/- 7.3 SD). Mean number of prior DMARD: 1.4 (+/- 1.2 SD), mean number of prior BT was 0.8 (+/- 1.1). Mean time on CZP was 9.8 months (+/- 3.4 SD). A total of 71.4% were receiving CZP at 12-month assessment. Baseline predictors of response: lower prior number DMARD; low number prior BT; higher CRP, ESR, TJC, SJC, DAS28 and SDAI (