Glecaprevir/pibrentasvir for hepatitis C virus genotype 3 patients with cirrhosis and/or prior treatment experience: A partially randomized phase 3 clinical trial.

This study assessed the efficacy and safety of ribavirin-free coformulated glecaprevir/pibrentasvir (G/P) in patients with hepatitis C virus genotype 3 infection with prior treatment experience and/or compensated cirrhosis, a patient population with limited treatment options. SURVEYOR-II, Part 3 was a partially randomized, open-label, multicenter, phase 3 study. Treatment-experienced (prior interferon or pegylated interferon ± ribavirin or sofosbuvir plus ribavirin ± pegylated interferon therapy) patients without cirrhosis were randomized 1:1 to receive 12 or 16 weeks of G/P (300 mg/120 mg) once daily. Treatment-naive or treatment-experienced patients with compensated cirrhosis were treated with G/P for 12 or 16 weeks, respectively. The primary efficacy endpoint was the percentage of patients with sustained virologic response at posttreatment week 12 (SVR12). Safety was evaluated throughout the study. There were 131 patients enrolled and treated. Among treatment-experienced patients without cirrhosis, SVR12 was achieved by 91% (20/22; 95% confidence interval [CI], 72-97) and 95% (21/22; 95% CI, 78-99) of patients treated with G/P for 12 or 16 weeks, respectively. Among those with cirrhosis, SVR12 was achieved by 98% (39/40; 95% CI, 87-99) of treatment-naive patients treated for 12 weeks and 96% (45/47; 95% CI, 86-99) of patients with prior treatment experience treated for 16 weeks. No adverse events led to discontinuation of study drug, and no serious adverse events were related to study drug. Conclusion: Patients with hepatitis C virus genotype 3 infection with prior treatment experience and/or compensated cirrhosis achieved high SVR12 rates following 12 or 16 weeks of treatment with G/P. The regimen was well tolerated. (Hepatology 2018;67:514-523).

Sufficient sampling for asymptotic minimum species richness estimators.

Biodiversity sampling is labor intensive, and a substantial fraction of a biota is often represented by species of very low abundance, which typically remain undetected by biodiversity surveys. Statistical methods are widely used to estimate the asymptotic number of species present, including species not yet detected. Additional sampling is required to detect and identify these species, but richness estimators do not indicate how much sampling effort (additional individuals or samples) would be necessary to reach the asymptote of the species accumulation curve. Here we develop the first statistically rigorous nonparametric method for estimating the minimum number of additional individuals, samples, or sampling area required to detect any arbitrary proportion (including 100%) of the estimated asymptotic species richness. The method uses the Chao1 and Chao2 nonparametric estimators of asymptotic richness, which are based on the frequencies of rare species in the original sampling data. To evaluate the performance of the proposed method, we randomly subsampled individuals or quadrats from two large biodiversity inventories (light trap captures of Lepidoptera in Great Britain and censuses of woody plants on Barro Colorado Island [BCI], Panama). The simulation results suggest that the method performs well but is slightly conservative for small sample sizes. Analyses of the BCI results suggest that the method is robust to nonindependence arising from small-scale spatial aggregation of species occurrences. When the method was applied to seven published biodiversity data sets, the additional sampling effort necessary to capture all the estimated species ranged from 1.05 to 10.67 times the original sample (median approximately equal to 2.23). Substantially less effort is needed to detect 90% of the species (0.33-1.10 times the original effort; median approximately equal to 0.80). An Excel spreadsheet tool is provided for calculating necessary sampling effort for either abundance data or replicated incidence data.