NA inhibitors (oseltamivir and zanamivir) have been studied for both treatment and prophylaxis with the human influenza A subtypes H1, H2, and H3 as well as influenza B (Table 7 ) [80] [81] [82] . In animal models with HPAI H5N1, their efficacy has been well documented, with improved survival rates seen after infection [83] [84] [85] . Oseltamivir has been used in avian influenza outbreaks involving H7N7 and HPAI H5N1, and therapy with oseltamivir has been shown to decrease the viral load in nasal secretions in patients infected with HPAI H5N1 [11, 86, 87] . Resistance to oseltamivir has been documented in a HPAI H5N1 subtype in a Vietnamese girl treated with 75 mg daily for 4 days as post-exposure prophylaxis [68] . The NA glycoprotein had a histidine to tyrosine substitution at position 274, conveying a markedly higher IC50 for oseltamivir [68, 88] . In one study, the viral count of HPAI H5N1 in nasal secretions did not decrease with the administration of oseltamivir when the H5N1 isolate carried this resistance mutation [68] . However, resistance produced by this change may be overcome with higher doses of oseltamivir in vitro, and this change has not been documented to confer resistance to zanamivir [88] .