Clinical effectiveness of oseltamivir for influenza A(H1N1) virus with H274Y neuraminidase mutation

• Published in: The Journal of infection Vol. 59; no. 3; pp. 207 - 212
• Main Authors: Kawai, Naoki, Ikematsu, Hideyuki, Iwaki, Norio, Kondou, Kunio, Hirotsu, Nobuo, Kawashima, Takashi, Maeda, Tetsunari, Tanaka, Osame, Doniwa, Ken-ichi, Kashiwagi, Seizaburo
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Ltd 01-09-2009; Elsevier
• Subjects: Adolescent; Adult; Amino Acid Substitution; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiviral agents; Antiviral Agents - therapeutic use; Biological and medical sciences; Body Temperature; Child; Child, Preschool; General aspects; Human viral diseases; Humans; Infectious Disease; Infectious diseases; Influenza A Virus, H1N1 Subtype - drug effects; Influenza A Virus, H1N1 Subtype - genetics; Influenza A Virus, H1N1 Subtype - isolation & purification; Influenza A(H1N1); Influenza, Human - drug therapy; Influenza, Human - epidemiology; Medical sciences; Middle Aged; Mutation; Neuraminidase; Neuraminidase - antagonists & inhibitors; Neuraminidase - genetics; Oseltamivir; Oseltamivir - therapeutic use; Pharmacology. Drug treatments; Resistance; Treatment Outcome; Viral diseases; Viral diseases of the respiratory system and ent viral diseases; Young Adult; Influenza A(H1N1); Resistance; Oseltamivir; Mutation; Neuraminidase; Neuraminidase inhibitor; Enzyme; Enzyme inhibitor; Glycosylases; Infection; Glycosidases; Viral disease; Exo-α-sialidase; Hydrolases; Antiviral; Influenza A
• ISSN: 0163-4453; 1532-2742
• DOI: 10.1016/j.jinf.2009.07.002

Summary Objective To evaluate the clinical effectiveness of oseltamivir therapy started within 48 h of the onset for influenza A(H1N1) virus with H274Y neuraminidase (NA) mutation. Methods Virus was isolated before and four to six days after starting oseltamivir treatment from 73 outpatients with influenza A(H1N1) virus in the 2007–2008 and 2008–2009 seasons. NA inhibition assays (IC50 ) and sequence analyses were done using influenza viruses isolated from these patients. Body temperature was evaluated before and on the second, third, and fourth days after starting treatment. Results H274Y mutation was not shown in the 2007–2008 season (44 patients) and shown in all 29 patients in the 2008–2009 season by NA sequence analyses. The mean IC50 before oseltamivir treatment was significantly higher in 2008–2009 (319.3 ± 185.4 nM) than in 2007–2008 (1.5 ± 0.8 nM; p < .001). Patients ≤ 15 years with oseltamivir-resistant virus infection had a higher ratio of patients persisted virus after oseltamivir treatment than patients > 15 years (50% and 11.8%, respectively, p = 0.038), and a significant higher body temperature during oseltamivir treatment, compared to patients ≤15 years treated for oseltamivir-sensitive virus infection. Conclusion The clinical effectiveness of oseltamivir for the A(H1N1) virus was reduced in the 2008–2009 season compared with the previous season, especially in children, probably due to the H274Y mutation. Oseltamivir seems to be not recommended for children and patients with high-risk underlying diseases infected with H274Y mutated A(H1N1) virus.