Efficacy and safety of daclatasvir plus pegylated-interferon alfa 2a and ribavirin in previously untreated HCV subjects coinfected with HIV and HCV genotype-1: a Phase III, open-label study.

BACKGROUND: Daclatasvir (DCV) is a potent, pangenotypic, hepatitis C virus (HCV) non-structural protein 5A inhibitor with low potential for drug interactions with antiretroviral therapy (ART). We evaluated the safety and efficacy of DCV plus peginterferon alfa-2a/ribavirin (PegIFN/RBV) in HIV-1/HCV genotype-1-coinfected patients. METHODS: AI444043 (NCT01471574), an open-label, Phase III, single-arm, response-guided treatment (RGT) study included 301 patients. They received DCV doses of 30, 60 or 90 mg once daily (depending on concomitant ART), plus weight-based RBV (<75 kg, 1000 mg/day; or ≥75 kg, 1200 mg/day), and once-weekly PegIFN 180 µg, for 24 weeks. If required by RGT, PegIFN/RBV without DCV was extended for an additional 24 weeks of therapy. The primary endpoint was the proportion of patients with sustained virologic response at post-treatment Week 12 (SVR12). RESULTS: Overall, 224 (74%) patients achieved SVR12 and the lower bound of the 95% confidence interval was higher than the historic SVR rate with PegIFN/RBV alone (70 vs. 29%). Most common adverse events (AEs) were fatigue, neutropenia, anemia, asthenia and headache. On-treatment serious AEs occurred in 24/301 (8%) patients; 18/301 (6%) discontinued treatment due to AE. CONCLUSIONS: DCV + PegIFN/RBV led to sustained HCV virologic response in the majority of HIV-1-HCV-coinfected patients, regardless of concomitant ART. HIV control was not compromised and no new safety signals were identified. This study supports DCV use in HIV-1-HCV-coinfected patients, while allowing the vast majority of patients to remain on their existing ART regimen.

The Effectiveness of Noninvasive Interventions for Temporomandibular Disorders: A Systematic Review by the Ontario Protocol for Traffic Injury Management (OPTIMa) Collaboration.

OBJECTIVE: To determine the effectiveness and cost-effectiveness of noninvasive interventions for temporomandibular disorders (TMD). METHODS: We systematically searched MEDLINE, EMBASE, CINAHL, PsycINFO, and Cochrane Central register from 1990 to 2014 for effectiveness studies and the Cochrane Health Technology Assessment Database, EconLit, NHS Economic Evaluation Database, and Tufts Medical Center Cost-Effectiveness Analysis Register from 1990 to 2014 for cost-effectiveness studies. Random pairs of independent reviewers critically appraised eligible studies using the Scottish Intercollegiate Guidelines Network criteria. Evidence from eligible studies was synthesized using best-evidence synthesis methodology. RESULTS: Our search for effectiveness studies yielded 16,995 citations; 31 were relevant and 7 randomized controlled trials (published in 8 articles) had a low risk of bias. We found no relevant cost-effectiveness studies. The evidence suggests that for persistent TMD: (1) cognitive-behavioral therapy and self-care management lead to similar improvements in pain and disability but cognitive-behavioral therapy is more effective for activity interference and depressive symptoms; (2) cognitive-behavioral therapy combined with usual treatment provides short-term benefits in pain and ability to control pain compared with usual treatment alone; (3) intraoral myofascial therapy may reduce pain and improve jaw opening; and (4) structured self-care management may be more effective than usual treatment. The evidence suggests that occlusal devices may not be effective in reducing pain and improving motion for TMD of variable duration. Evidence on the effectiveness of biofeedback is inconclusive. DISCUSSION: The available evidence suggests that cognitive-behavioral therapy, intraoral myofascial therapy, and self-care management are therapeutic options for persistent TMD.