A novel substitution in NS5A enhances the resistance of hepatitis C virus genotype 3 to daclatasvir.

Hepatitis C virus (HCV) genotype 3 presents a high level of both baseline and acquired resistance to direct-acting antivirals (DAAs), particularly those targeting the NS5A protein. To understand this resistance we studied a cohort of Brazilian patients treated with the NS5A DAA, daclatasvir and the nucleoside analogue, sofosbuvir. We observed a novel substitution at NS5A amino acid residue 98 [serine to glycine (S98G)] in patients who relapsed post-treatment. The effect of this substitution on both replication fitness and resistance to DAAs was evaluated using two genotype 3 subgenomic replicons. S98G had a modest effect on replication, but in combination with the previously characterized resistance-associated substitution (RAS), Y93H, resulted in a significant increase in daclatasvir resistance. This result suggests that combinations of substitutions may drive a high level of DAA resistance and provide some clues to the mechanism of action of the NS5A-targeting DAAs.

An Analysis of Drug-Related Problems in the Neurology Ward of a Tertiary Teaching Hospital: A Cross-Sectional Study.

Background and objective Drugs that act on the central nervous system have a high potential to cause drug-related problems (DRPs). A clinical pharmacist aided by collaborative efforts within an interdisciplinary healthcare team can prevent, detect, and resolve DRPs, thereby contributing to the promotion of medication safety and improving the quality of life of individuals under care. This study aimed to assess DRPs identified in the neurology ward of a tertiary hospital from February 2016 to November 2019. Methods This was a descriptive study with a cross-sectional and retrospective design involving secondary data collected from pharmaceutical care (PC) records. Student's t-tests, Pearson correlation coefficients, Poisson models, and logistic regression models were used to analyze the associations between age, number and type of medications, duration of hospitalization, and the occurrence of DRPs. Results A total of 130 patients were included in the study, and a total of 266 DRPs were detected, with 93 patients experiencing more than one DRP and 37 not presenting any DRPs. Necessity-related DRPs were the most prevalent (46.6%) type, followed by safety-related DRPs (28.6%). The prevalence of safety-related DRPs was higher in individuals older than 60 years (p<0.001). Conclusions Of note, 84.6% of the interventions suggested by pharmacists to resolve DRPs were accepted by the healthcare team. The high number of DRPs found underscores the importance of the clinical role of the pharmacist and interprofessional collaboration in the care of neurological patients, especially in the pharmaceutical follow-up of elderly individuals.