Clinical effectiveness of oseltamivir and zanamivir for treatment of influenza A virus subtype H1N1 with the H274Y mutation: a Japanese, multicenter study of the 2007-2008 and 2008-2009 influenza seasons.
BACKGROUND
Influenza A virus subtype H1N1 with the H274Y mutation emerged and spread worldwide. However, the clinical effectiveness of the neuraminidase inhibitors, oseltamivir and zanamivir, has not been adequately reevaluated.


METHODS
Data from 164 patients with H1N1 virus infection and 59 patients with H3N2 virus infection during the 2008-2009 influenza season and 68 patients with H1N1 virus infection during the 2007-2008 influenza season who received a neuraminidase inhibitor were analyzed. The duration of fever (body temperature 37.5 degrees C) after the first dose of oseltamivir or zanamivir and from onset of symptoms was calculated from patient reports. The influenza virus was isolated, and its subtype was determined by hemagglutinin inhibition assay and polymerase chain reaction. The H274Y neuraminidase mutation status was determined by sequencing the neuraminidase segment.


RESULTS
Of 68 patients with H1N1 virus infection during the 2007-2008 season, 41 were treated with oseltamivir, and 27 were treated with zanamivir. During the 2008-2009 season, 77 patients with H1N1 virus infection were treated with oseltamivir, and 87 were treated with zanamivir; 31 and 28 patients with H3N2 virus infection were treated with oseltamivir and zanamivir, respectively. All 49 analyzed H1N1 virus isolates obtained during the 2008-2009 season, but none of the isolates obtained during the 2007-2008 season, contained the H274Y mutation. The mean +/- standard deviation duration of fever after the start of oseltamivir therapy was significantly longer for patients with H1N1 virus infection (49.1+/-30.2 h) than it was for patients with H3N2 virus infection (33.7+/-20.1 h; P < .01) during the 2008-2009 season and patients with H1N1 virus infection during the 2007-2008 season (32.0+/-18.9 h; P < .001). The duration of fever was significantly longer after the first dose of oseltamivir than it was after the first dose of zanamivir for patients with H1N1 virus infection during the 2008-2009 season (P <.001). The duration of fever from onset of H1N1 virus infection was significantly longer for children 15 years of age during 2008-2009 (70.6+/-34.5 h) than it was for such children during 2007-2008 (48.4+/-21.2).


CONCLUSIONS
The effectiveness of oseltamivir, but not that of zanamivir, decreased significantly for H1N1 virus infection during the 2008-2009 season.
Kawai
Naoki
N
Japan Physicians Association, Tokyo, Japan. nkawai@city.gifu.med.or.jp
Ikematsu
Hideyuki
H
Hirotsu
Nobuo
N
Maeda
Tetsunari
T
Kawashima
Takashi
T
Tanaka
Osame
O
Yamauchi
Satoshi
S
Kawamura
Kenichi
K
Matsuura
Shinro
S
Nishimura
Mika
M
Iwaki
Norio
N
Kashiwagi
Seizaburo
S
D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D024882:Drug Resistance, Viral; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D005260:Female; D005334:Fever / Q000453:epidemiology; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000235:genetics*; D007251:Influenza, Human / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009439:Neuraminidase / Q000037:antagonists & inhibitors / Q000235:genetics*; D053139:Oseltamivir / Q000627:therapeutic use*; D013997:Time Factors; D053243:Zanamivir / Q000627:therapeutic use*
D000998:Antiviral Agents; D004791:Enzyme Inhibitors; D053139:Oseltamivir; D009439:Neuraminidase; D053243:Zanamivir