Safety and Antiviral Activity of Albinterferon Alfa-2b Dosed Every Four Weeks in Genotype 2/3 Chronic Hepatitis C Patients
A phase 2, randomized, multicenter, open-label study evaluated the safety and efficacy of albinterferon alfa-2b in interferon-alpha treatment-naïve patients with genotype 2/3, chronic hepatitis C virus infection.
Forty-three patients were randomly assigned in a 1:1 ratio to receive subcutaneous albinterferon alfa-2b 1500 microg every 4 weeks (q4wk) or every 2 weeks (q2wk) with oral ribavirin 800 mg/day for 24 weeks. Primary efficacy end point was sustained virologic response (undetectable hepatitis C virus RNA 24 weeks after completion of treatment). Insulin resistance was also assessed.
The safety of albinterferon alfa-2b was acceptable, with a similar adverse event profile in both treatment arms. Discontinuation as a result of adverse events occurred in 4.5% and 14.3% of patients in the q4wk and q2wk arms, respectively. No dose reductions caused by adverse events were reported in the q4wk arm versus 9.5% in the q2wk arm. Rapid viral response rates at week 4 were 68.2% and 76.2% for the q4wk and q2wk arms, respectively; the corresponding sustained virologic response rates were 77.3% and 61.9%. Insulin resistance at baseline was significantly associated with lower sustained virologic response rates independent of body mass index.
Albinterferon alfa-2b administered at 4-week intervals was safe and well-tolerated and demonstrated significant antiviral activity in patients with genotype 2/3, chronic hepatitis C virus. Insulin resistance appeared to have an independent effect on treatment response.
Available from: Richard A Lempicki
- "One recently developed formulation of IFN is albinterferon alfa-2b (albIFN), a novel, long-acting, genetic fusion polypeptide of recombinant human albumin and interferon alfa-2b [Subramanian et al., 2007]. This formulation extended the half-life of the recombinant polypeptide product to about 200 hr while maintaining biological activity over a 14-to 28-day interval [Subramanian et al., 2007; Bain et al., 2008]. In three separate randomized controlled trials in HCV monoinfected genotype 1 or genotype 2/3 infections, albIFN administered q2week or q4week demonstrated comparable efficacy to PegIFN [Nelson et al., 2010; Zeuzem et al., 2010]. "
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ABSTRACT: The effect of different formulations of interferon on therapeutic response in patients coinfected with HIV and HCV is unclear. In this study, the safety, tolerability, viral kinetics (VK) modeling and host responses among HIV/HCV coinfected patients treated with pegylated-IFN or albinterferon alfa-2b (AlbIFN) with weight-based ribavirin were compared. Three trials treated 57 HIV/HCV coinfected genotype-1 patients with PegIFN alfa-2b (1.5 µg/kg/week) (n = 30), PegIFN alfa-2a (180 µg/week) (n = 10), and AlbIFN (900 µg/q2week) (n = 17) in combination with weight-based ribavirin (RBV). HCV RNA, safety labs, and interferon stimulated gene expression (ISG) was evaluated. Adverse events were documented at all study visits. HCV viral kinetics using a full pharmacokinetic/pharmacodynamic model was also evaluated. Baseline patient characteristics were similar across the three studies. All three formulations exhibited comparable safety and tolerability profiles and efficacy. VK/PK/PD parameters for all three studies as measured by mean efficiency and rate of infected cell loss were similar between the three groups. Host responses (ISG expression and immune activation markers) were similar among the three groups. All three regimens induced significant ISG at week 4 (P < 0.05) and ISG expression strongly correlated with therapeutic response (r = 0.65; P < 0.01). In summary, a comprehensive analysis of responses to three different interferon formulations in HIV/HCV coinfected patients demonstrated similar effects. Notably, interferon-based therapy results in a blunted host response followed by modest antiviral effect in HIV/HCV coinfected patients. This suggests that future treatment options that do not rely on host immune responses such as direct antiviral agents would be particularly beneficial in these difficult to treat patients. J. Med. Virol. © 2013 Wiley Periodicals, Inc.
Journal of Medical Virology 02/2014; 86(2). DOI:10.1002/jmv.23773 · 2.35 Impact Factor
Available from: Payam Behzadi
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ABSTRACT: Pseudomonas aeruginosa is an important bacterial pathogen which causes different infectious diseases such as wound and skin lesion infections. The main goal of this study was to induce eventual apoptotic reactions in ultraviolet-exposed colonies of Pseudomonas aeruginosa.
The colonies of Pseudomonas aeruginosa were irradiated by UVB light; then, the DNA molecules of control and UVB-exposed colonies were extracted. Eventually, the extracted DNA molecules mixed in loading dye were run in 1% agarose gel containing ethidium bromide.
No unusual pattern like DNA laddering bands or smear, were detected upon the 1% agarose gel.
Through the applied protocol in this survey, the UVB radiation is not able to trigger apoptosis pathway in UV light exposed colonies of Pseudomonas aeruginosa. It seems that the cytoprotective property of Heat shock proteins inhibit the inducing effect of UVB light in irradiated colonies of Pseudomonas aeruginosa.
Roumanian archives of microbiology and immunology 70(2):74-7.
Millimeter Wave and Far-Infrared Technology, 1989. ICMWFT '89. International Conference on; 02/1989
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