Has Oseltamivir Been Shown to Be Effective for Treatment of H5N1 Influenza?

EDITORIAL COMMENTARY

Has Oseltamivir Been Shown to Be Effective for Treatment of H5N1 Influenza?

http://www.journals.uchicago.edu/doi/full/10.1086/656317
This issue of JID features an article by Adisasmito et al. It reviews previous clinical report, case series etc to determine whether oseltamivir is effective for treatment of H5N1 influenza.

In total, 308 cases were identified from 12 countries: 41 from Azerbaijan, Hong Kong SAR, Nigeria, Pakistan, and Turkey (from clinical records); 175 from Egypt and Indonesia (from various sources); and 92 from Bangladesh, Cambodia, China, Thailand, and Vietnam (from various publications). Overall crude survival was 43.5%; 60% of patients who received 1 dose of oseltamivir alone (OS⁺) survived versus 24% of patients who had no evidence of anti‐influenza antiviral treatment (OS⁻) ( ). Survival rates of OS⁺ groups were significantly higher than those of OS⁻ groups; benefit persisted with oseltamivir treatment initiation 6–8 days after symptom onset. Multivariate modeling showed 49% mortality reduction from oseltamivir treatment.

It is interesting to note that 14 cases in the Adisasmito report were treated with higher than standard dosages and 7 (50%) survived; 20 were treated for longer than 5 days (median, 7 days) and 15 (75%) survived. In view of the need for better treatment and the safety data available on higher dosages (150 mg twice daily) and longer durations of oseltamivir treatment, it seems reasonable to adopt the WHO proposed treatment of a higher dosage and duration of 10 days for H5N1 influenza and possibly all cases of influenza pneumonia. Finally, parenteral treatment with either the unapproved peramivir or zanamivir preparations may be best for this severe disease.

In summary, the combined experience with oseltamivir treatment by Adisasmito et al supports the belief that oseltamivir given orally at approved dosages for 5 days is beneficial for treatment of H5N1 influenza, particularly if treatment is started early in the course of illness. However, improvement in therapy is needed, and available data suggest oral therapy with a higher dosage (150 mg twice daily) and a longer duration (7–10 days) or parenteral therapy with peramivir or zanamivir are likely to improve on the standard oral oseltamivir treatment regimen.