No abstract

Oseltamivir treatment of influenza illness reduces LRTCs, antibiotic use, and hospitalization in both healthy and "at-risk" adults.

Our objective was to evaluate the benefit of early treatment of influenza illness using oral oseltamivir. This open-label, multicentre international study investigated the relationship between the interval from illness onset to first dose (time-to-treatment) and illness duration in the intent-to-treat infected population using accelerated failure time (AFT) modelling. A total of 1426 patients (12-70 years) presenting within 48 h of the onset of influenza symptoms were treated with oseltamivir 75 mg twice a day for 5 days during the 1999-2000 influenza season; 958 (67%) had laboratory-confirmed influenza virus infection. Earlier intervention was associated with shorter illness duration (P < 0.0001). Initiation of therapy within the first 12 h after fever onset reduced the total median illness duration by 74.6 h (3.1 days; 41%) more than intervention at 48 h. Intermediate interventions reduced the illness proportionately compared with 48 h. In addition, the earlier administration of oseltamivir further reduced the duration of fever, severity of symptoms and the times to return to baseline activity and health scores. Oseltamivir was well tolerated. The most common adverse events were nausea and vomiting, which were transient and generally occurred only with first dosing. When oseltamivir was taken with food, the tolerability was enhanced. The overall discontinuation rate was low (1.8%). In conclusion, the IMPACT study demonstrated that earlier initiation of oral oseltamivir therapy increased its therapeutic effects, which were seen at every time point of intervention and were progressive. Thus, early presentation, diagnosis and treatment of patients with influenza maximized the benefits of oseltamivir therapy.

As there is currently a lack of consensus on the most appropriate dose and duration of peginterferon alfa-2a (PEG-IFNa-2a) therapy in hepatitis B e antigen (HBeAg)-positive patients, the efficacy and safety of either 24 or 48 weeks' duration and 90 lg/week or 180 lg/week doses were compared. HBeAg-positive patients (n 5 544; 34% genotype B, 51% genotype C) were randomized to receive PEG-IFNa-2a (2 3 2 factorial design) for 24 or 48 weeks and at 90 lg/week or 180 lg/week and included in the per-protocol population. The primary efficacy endpoint of the noninferiority study was HBeAg seroconversion 6 months posttreatment. The prespecified odds ratio (OR) noninferiority margin was 1.88 with a one-sided significance level of 0.025. The highest rates of HBeAg seroconversion 6 months posttreatment were in the 180/48 arm (36.2% versus 14.1%-25.8% in the other arms). When the dose and duration arms were pooled, the OR for noninferiority of 24 weeks versus 48 weeks was 2.17 (95% confidence interval [CI] 1.43, 3.31; P 5 0.749) and for 90 lg versus 180 lg was 1.79 (95% CI 1.18, 2.72; P 5 0.410). As the upper limit of the 95% CI of the ORs were >1.88, 24 weeks were inferior to 48 weeks and 90 lg/week was inferior to 180 lg/week. The highest rates of response in the 180/48 arm were achieved by patients with HBsAg <1,500 IU/mL at Week 12 (58%) or Week 24 (57%), whereas patients with HBsAg >20,000 IU/mL did not respond. Adverse events were typical of those associated with PEG-IFNa-2a. Conclusion: Compared with lower doses and shorter durations, the licensed PEG-IFNa-2a treatment regimen (180lg/ 48 weeks) was the most efficacious and beneficial for HBeAg-positive patients predominantly infected with hepatitis B virus genotypes B or C. (HEPATOLOGY 2011;54:1591-1599 P eginterferon alfa-2a (40 kD; PEG-IFNa-2a) has proven efficacy in hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) 1 and is one of the first-line drugs recommended for CHB by all international treatment guidelines. 2-4Although the licensed dose and duration of PEG-IFNa-2a is 180 lg/week for 48 weeks, there is currently a lack of consensus on the most appropriate dose and duration, which is reflected in varying recommendations in international guidelines. The European Association for the Study of the Liver (EASL) and American Association for the Study of Liver Diseases (AASLD) guidelines recommend 48 weeks of treatment, but EASL guidelines do not provide dose information for any of the antiviral agents recommended 2 ; Asian Pacific Association for the Study of the Liver (APASL) guidelines recommend 90-

These data demonstrate durable efficacy of enfuvirtide plus OB over 48 weeks.