Oral oseltamivir in human experimental influenza B infection

Oseltamivir is the prodrug of Ro64-0802 (GS4071), a potent and selective in hibitor of influenza A and B virus neuraminidases, Three randomized, double -blind, placebo-controlled, parallel-group studies evaluated oral oseltamiv ir for early treatment (75 or 150 mg twice daily for 5 days) or prevention (75 mg once or twice daily for 7 days) of experimental influenza B virus in fection in healthy susceptible adults. Treatment study A (n=60) demonstrate d similar trends to treatment study B (n=117), in which 75 mg doses of osel tamivir introduced 24 h after inoculation reduced median area under curve ( AUC) virus titre (oseltamivir, 22.7; placebo, 131.1 log(10) TCID50 x h/ml; P=0.002) and duration of viral shedding (oseltamivir, 23.9 h; placebo, 95.8 h; P=0.0005). In prevention study C (n=58), oseltamivir did not reduce inf ection rates (85 versus 84%) but significantly reduced median AUC virus tit re (10.0 versus 66.9 log(10) TCID50 x h/ml; P=0.03) and duration of viral s hedding (36 versus 84 h; P=0.03) compared with placebo. Oseltamivir was wel l tolerated. No emergence of drug-resistant variants was detected by testin g last-day isolates (n=112) in neuraminidase inhibition assays. These resul ts indicate that oseltamivir has significant antiviral activity in experime ntal human influenza B virus infection when used for prophylaxis or early t reatment.