title: Determinants of antiviral effectiveness in influenza virus A subtype H5N1.
abstract: BACKGROUND
  Oseltamivir is widely used as treatment for influenza virus A subtype H5N1 (hereafter, "H5N1") infection but, like any intervention, is not always effective.
  
  
  METHODS
  We used Avian Influenza Registry data from 10 countries to examine the risk of death in 215 patients with confirmed H5N1 infection who were treated with oseltamivir, according to viral clade, age, respiratory failure, and adjunctive treatment with corticosteroids or antibiotics.
  
  
  RESULTS
  The median age of infected individuals was 18 years, and 50% were male. The highest fatality rate occurred in a country with clade 2.1 virus circulation, and the lowest occurred in countries with clade 2.2 virus circulation (P < .001). In univariate analyses, age of ≤5 years and treatment ≤2 days after symptom onset were protective against fatality. When accounting for all risk factors, early initiation of oseltamivir was found to be particularly effective in individuals without respiratory failure (odds ratio, 0.17; P = .04). Patients who had advanced respiratory failure requiring ventilatory support at the time of oseltamivir initiation were more likely to die from the episode of H5N1 infection than patients who did not (P < .001). Adjunctive therapy did not improve the likelihood of surviving the episode.
  
  
  CONCLUSIONS
  Oseltamivir is especially effective for treating H5N1 infection when given early and before onset of respiratory failure. The effect of viral clade on fatality and treatment response deserves further investigation.
authors.affiliation: Faculty of Medicine, Chinese University of Hong Kong, Kowloon, Hong Kong Special Administrative Region.
authors.forename: Paul K S
authors.initials: PK
authors.lastname: Chan
authors.forename: Nelson
authors.initials: N
authors.lastname: Lee
authors.forename: Mukhtiar
authors.initials: M
authors.lastname: Zaman
authors.forename: Wiku
authors.initials: W
authors.lastname: Adisasmito
authors.forename: Richard
authors.initials: R
authors.lastname: Coker
authors.forename: Wanna
authors.initials: W
authors.lastname: Hanshaoworakul
authors.forename: Viktor
authors.initials: V
authors.lastname: Gasimov
authors.forename: Ahmet Faik
authors.initials: AF
authors.lastname: Oner
authors.forename: Nazim
authors.initials: N
authors.lastname: Dogan
authors.forename: Owen
authors.initials: O
authors.lastname: Tsang
authors.forename: Bounlay
authors.initials: B
authors.lastname: Phommasack
authors.forename: Sok
authors.initials: S
authors.lastname: Touch
authors.forename: Ebun
authors.initials: E
authors.lastname: Bamgboye
authors.forename: Anna
authors.initials: A
authors.lastname: Swenson
authors.forename: Stephen
authors.initials: S
authors.lastname: Toovey
authors.forename: Nancy A
authors.initials: NA
authors.lastname: Dreyer
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000494:pharmacology; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D053124:Influenza A Virus, H5N1 Subtype / Q000187:drug effects*; D007251:Influenza, Human / Q000150:complications / Q000188:drug therapy* / Q000401:mortality / Q000821:virology*; D008297:Male; D008875:Middle Aged; D053139:Oseltamivir / Q000008:administration & dosage* / Q000494:pharmacology; D012131:Respiratory Insufficiency / Q000401:mortality / Q000821:virology; D055502:Secondary Prevention; D016019:Survival Analysis; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D053139:Oseltamivir