Factors associated with clinical and virological response in patients treated with oseltamivir or zanamivir for influenza A during the 2008–2009 winter

International audienceOseltamivir or zanamivir are effective in outpatients with seasonal influenza; however, factors associated with response have been incompletely described. During the 2008/2009 epidemic, in a randomized trial for influenza A-infected outpatients, clinical (time to alleviation of flu-related symptoms) and virological (rate of patients with day 2 nasal viral load 14 (HR, 0.47; 0.32–0.70), viral load ≥5 log cgeq/µL (HR, 0.63; 0.43–0.93), and initiation of antibiotics (HR, 0.30; 0.12–0.76); a lower virological response was associated with female gender (OR, 0.45; 0.21–0.96), baseline viral load ≥5 log cgeq/µL (OR, 0.40; 0.20–0.84) and days 0–2 incomplete compliance (OR, 0.31; 0.10–0.98). For zanamivir, virological response was associated with age ≥50 years (OR, 0.29; 0.10–0.85) and initiation of antibiotics at baseline (OR, 4.24; 1.07–17.50). Factors associated with lower response to neuraminidase inhibitors in outpatients appeared to be easily identifiable during routine clinical examination and, when appropriate, by nasal sampling at baseline. The unknown association between gender and response to oseltamivir was not explained by compliance

In Vivo Influenza Virus-Inhibitory Effects of the Cyclopentane Neuraminidase Inhibitor RWJ-270201

The cyclopentane influenza virus neuraminidase inhibitor RWJ-270201 was evaluated against influenza A/NWS/33 (H1N1), A/Shangdong/09/93 (H3N2), A/Victoria/3/75 (H3N2), and B/Hong Kong/05/72 virus infections in mice. Treatment was by oral gavage twice daily for 5 days beginning 4 h pre-virus exposure. The influenza virus inhibitor oseltamivir was run in parallel, and ribavirin was included in studies with the A/Shangdong and B/Hong Kong viruses. RWJ-270201 was inhibitory to all infections using doses as low as 1 mg/kg/day. Oseltamivir was generally up to 10-fold less effective than RWJ-270201. Ribavirin was also inhibitory but was less tolerated by the mice at the 75-mg/kg/day dose used. Disease-inhibitory effects included prevention of death, lessening of decline of arterial oxygen saturation, inhibition of lung consolidation, and reduction in lung virus titers. RWJ-270201 and oseltamivir, at doses of 10 and 1 mg/kg/day each, were compared with regard to their effects on daily lung parameters in influenza A/Shangdong/09/93 virus-infected mice. Maximum virus titer inhibition was seen on day 1, with RWJ-270201 exhibiting the greater inhibitory effect, a titer reduction of >10(4) cell culture 50% infective doses (CCID(50))/g. By day 8, the lung virus titers in mice treated with RWJ-270201 had declined to 10(1.2) CCID(50)/g, whereas titers from oseltamivir-treated animals were >10(3) CCID(50)/g. Mean lung consolidation was also higher in the oseltamivir-treated animals on day 8. Both neuraminidase inhibitors were well tolerated by the mice. RWJ-270201 was nontoxic at doses as high as 1,000 mg/kg/day. These data indicate potential for the oral use of RWJ-270201 in the treatment of influenza virus infections in humans