Adherence to once-daily and twice-daily direct acting antiviral therapy for hepatitis C infection among people with recent injection drug use or current opioid agonist therapy

BACKGROUND This study investigated adherence and associated factors among people with recent injection drug use (IDU) or current opioid agonist therapy (OAT) and compared once-daily to twice-daily hepatitis C virus (HCV) direct-acting antiviral (DAA) therapy. METHODS SIMPLIFY and D3FEAT are international, multicenter studies that recruited participants with recent IDU (previous 6 months; SIMPLIFY, D3FEAT) or current OAT (D3FEAT) between March 2016 and February 2017 in 8 countries. Participants received sofosbuvir/velpatasvir (once daily; SIMPLIFY) or paritaprevir/ritonavir/ombitasvir, dasabuvir (twice daily) ± ribavirin (D3FEAT) for 12 weeks administered in electronic blister packs. We evaluated overall adherence (proportion of prescribed doses taken) and nonadherence (<90% adherent) between dosing patterns. RESULTS Of 190 participants, 184 (97%) completed treatment. Median adherence was 92%, with higher adherence among those receiving once-daily vs twice-daily therapy (94% vs 87%, P = .005). Overall, 40% of participants (n = 76) were nonadherent (<90% adherent). Recent stimulant injecting (odds ratio [OR], 2.48 [95% confidence interval {CI}, 1.28-4.82]), unstable housing (OR, 2.18 [95% CI, 1.01-4.70]), and twice-daily dosing (OR, 2.81 [95% CI, 1.47-5.36]) were associated with nonadherence. Adherence decreased during therapy. Sustained virologic response was high in nonadherent (89%) and adherent populations (95%, P = .174), with no difference in SVR between those who did and did not miss 7 consecutive doses (92% vs 93%, P = .897). CONCLUSIONS This study demonstrated high adherence to once- and twice-daily DAA therapy among people with recent IDU or currently receiving OAT. Nonadherence described did not impact treatment outcomes, suggesting forgiveness to nonadherence

Adherence to sofosbuvir and velpatasvir among people with chronic HCV infection and recent injection drug use:The SIMPLIFY study

BACKGROUND:This study investigated treatment adherence among people with recent injecting drug use in a study of sofosbuvir/velpatasvir therapy for HCV infection. METHODS:SIMPLIFY is an international open-label, single-arm multicentre study that recruited participants with recent injecting drug use (previous six months) and chronic HCV genotype (G) 1-6 infection between March and October 2016 in seven countries (19 sites). Participants received sofosbuvir/velpatasvir once-daily for 12 weeks administered in a one-week electronic blister pack (records the time and date of each dose) for 12 weeks. We evaluated non-adherence (<90% adherent) as measured by electronic blister-pack assessed using logistic regression and generalised estimating equations (continuous) with detailed analyses of dosing dynamics. RESULTS:Among 103 participants, 97% (n = 100) completed treatment. Median adherence to therapy was 94%. Overall, 32% (n = 33) were considered non-adherent (<90% adherence). Adherence significantly decreased over the course of therapy. Recent stimulant injecting (cocaine and/or amphetamines) at treatment initiation and during treatment was independently associated with non-adherence. Inconsistent dose timing (standard deviation of daily dose timing of ≥240 min) was also independently associated with non-adherence to therapy. Factors associated with inconsistent dose timing included lower levels of education and recent stimulant injecting. SVR was similar among adherent and non-adherent populations (94% vs. 94%, P = 0.944). CONCLUSION:This study demonstrated high adherence to once-daily sofosbuvir/velpatasvir therapy among a population of people with recent injecting drug use. Recent stimulant injecting prior to and during DAA therapy and inconsistent dose-timing during treatment was associated with non-adherence. However, there was no impact of non-adherence on response to therapy, suggesting that adherence is not a significant barrier to successful DAA therapy in people with recent injecting drug use.Evan B.Cunningham, Janaki Amin, Jordan J.Feld, Julie Bruneau, Olav Dalgard, Jeff Powis ... et al

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Data from: Multiple polyploidy events in the early radiation of nodulating and non-nodulating legumes

Unresolved questions about evolution of the large and diverse legume family include the timing of polyploidy (whole-genome duplication; WGDs) relative to the origin of the major lineages within the Fabaceae and to the origin of symbiotic nitrogen fixation. Previous work has established that a WGD affects most lineages in the Papilionoideae and occurred some time after the divergence of the papilionoid and mimosoid clades, but the exact timing has been unknown. The history of WGD has also not been established for legume lineages outside the Papilionoideae. We investigated the presence and timing of WGDs in the legumes by querying thousands of phylogenetic trees constructed from transcriptome and genome data from 20 diverse legumes and 17 outgroup species. The timing of duplications in the gene trees indicates that the papilionoid WGD occurred in the common ancestor of all papilionoids. The earliest diverging lineages of the Papilionoideae include both nodulating taxa such as the genistoids (e.g. lupin), dalbergioids (e.g. peanut), phaseoloids (e.g. beans), and galegoids (= Hologalegina, e.g. clovers), and clades with non-nodulating taxa including Xanthocercis and Cladrastis (evaluated in this study). We also found evidence for several independent WGDs near the base of other major legume lineages, including the Mimosoid-Cassiinae-Caesalpinieae (MCC), Detarieae, and Cercideae clades. Nodulation is found in the MCC and papilionoid clades, both of which experienced ancestral WGDs. However, there are numerous non-nodulating lineages in both clades, making it unclear whether the phylogenetic distribution of nodulation is due to independent gains or a single origin followed by multiple losses

protein-sequence alignments

Peptide alignments for orthogroup clusters in the project, calculated using MUSCLE. These are multifasta alignment files

single copy trees

Low-copy trees used to estimate a species phylogeny using MP-EST methods

DNA alignments

cDNA alignments for all gene families in the project, made using pal2nal. These are multifasta alignment files