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Intravenous remdesivir (RDV) is US Food and Drug Administration–approved for hospitalized and nonhospitalized individuals with coronavirus disease 2019. RDV undergoes intracellular metabolic activation to form the active triphosphate, GS‐443902, and other metabolites. Alternative administration routes, including localized pulmonary delivery, can lower systemic exposure and maximize exposure at the site of action. This study evaluated the pharmacokinetics (PK) and safety of inhaled RDV in healthy adults. This phase Ia, randomized, placebo‐controlled study evaluated inhaled RDV in healthy participants randomized 4:1 to receive RDV or placebo as single doses (4 cohorts) or multiple once‐daily doses (3 cohorts). Doses in cohorts 1–6 were administered as an aerosolized solution for inhalation through a sealed facemask; doses in cohort 7 were administered as an aerosolized solution for inhalation through a mouthpiece. Safety was assessed throughout the study. Seventy‐two participants were enrolled (inhaled RDV, n = 58 and placebo, n = 14). Following single RDV doses, RDV, GS‐704277, and GS‐441524 plasma PK parameters indicated dose‐proportional increases in area under the concentration‐time curve (AUC) extrapolated to infinite time, AUC from time zero to last quantifiable concentration, and maximum observed concentration. Analyte plasma concentrations after multiple RDV doses were consistent with those for single‐dose RDV. Analyte plasma exposures were lower when RDV was administered with a mouthpiece versus a sealed facemask. The most common adverse events included nausea, dizziness, and cough. Single‐ and multiple‐dose inhaled RDV exhibited linear and dose‐proportional plasma PK. Administration of RDV via inhalation was generally safe and well‐tolerated. [ABSTRACT FROM AUTHOR]

Aim: The combination of ledipasvir and sofosbuvir (LDV/SOF) has been approved for the treatment of various hepatitis C virus (HCV) genotypes across many countries. This article presents an integrated analysis of three prospective phase II/III trials in the Asia‐Pacific region to evaluate the efficacy and safety of 12 weeks of LDV/SOF in HCV genotype 2 patients without cirrhosis or with compensated cirrhosis. Methods: A total of 200 patients were included in the integrated analysis. The primary end‐point was the rate of sustained virologic response for 12 weeks after the end of therapy (SVR12), analyzed by fibrosis stage, treatment history, HCV genotype subtype, and presence of baseline resistance‐associated substitutions (RAS). Safety was evaluated by adverse events and laboratory abnormalities. Results: Twelve weeks of treatment with LDV/SOF was associated with high SVR12 rates (overall 98%) in patients with genotype 2 HCV, irrespective of fibrosis stage, treatment history, genotype 2 subtype, and presence of baseline non‐structural protein 5A resistance‐associated substitution (NS5A RAS), and LDV/SOF was well tolerated. Conclusions: Twelve weeks of treatment with LDV/SOF provides a highly effective and safe treatment for patients with genotype 2 HCV, including those with advanced fibrosis. As a ribavirin‐free and protease inhibitor‐free regimen with minimal on‐treatment monitoring requirements, LDV/SOF can potentially play a crucial role in achieving the WHO's goal of HCV elimination. [ABSTRACT FROM AUTHOR]

Background Hepatitis C virus (HCV) direct-acting antiviral therapy is effective among people receiving opioid substitution therapy (OST), but studies are limited by small numbers of nongenotype 1 (GT1) patients. The aim of this study was to evaluate the treatment completion, adherence, SVR12, and safety of sofosbuvir-based therapies in HCV patients receiving and not receiving OST. Methods Ten phase 3 studies of sofosbuvir-based regimens included ION (ledipasvir/sofosbuvir ± ribavirin for 8, 12, or 24 weeks in GT1), ASTRAL (sofosbuvir/velpatasvir for 12 weeks in GT1-6), and POLARIS (sofosbuvir/velpatasvir and sofosbuvir/velpatasvir/voxilaprevir in GT1-6). Patients with clinically significant drug use (last 12 months) or noncannabinoids detected at screening were ineligible. Results Among 4743 patients, 4% (n = 194) were receiving OST (methadone; n = 113; buprenorphine, n = 75; other, n = 6). Compared with those not receiving OST (n = 4549), those receiving OST (n = 194) were younger (mean age, 48 vs 54), more often male (73% vs 61%), GT3 (38% vs 17%), treatment-naïve (78% vs 65%), and cirrhotic (36% vs 23%). Among those receiving and not receiving OST, there was no significant difference in treatment completion (97% vs 99%, P =.06), SVR12 (94% vs 97%, P =.06), relapse (0.5% vs 2.1%, P =.19), adverse events (78% vs 77%, P =.79), or serious adverse events (3.6% vs 2.4%, P =.24). There was no difference in SVR12 in patients with cirrhosis (99% vs 95%, P =.25) or those with G3 (95% vs 95%, P =.77) in those receiving OST. Among patients receiving OST, SVR12 was high among those receiving methadone (95%) and buprenorphine (96%). Conclusion Sofosbuvir-based therapies are effective and safe in patients receiving OST. [ABSTRACT FROM AUTHOR]