BACKGROUND: Safe and effective antiviral agents are needed to prevent infection 
with influenza A and B virus. Oseltamivir (GS4104), which can be administered 
orally, is the prodrug of GS4071, a potent and selective inhibitor of 
influenzavirus neuraminidases. We studied the use of oseltamivir for long-term 
prophylaxis against influenza in two placebo-controlled, double-blind trials at 
different U.S. sites during the winter of 1997-1998.
METHODS: We randomly assigned 1559 healthy, nonimmunized adults 18 to 65 years 
old to receive either oral oseltamivir (75 mg given once or twice daily, for a 
total daily dose of 75 or 150 mg) or placebo for six weeks during a peak period 
of local influenzavirus activity. The primary end point with respect to efficacy 
was laboratory-confirmed influenza-like illness (defined as a temperature of at 
least 37.2 degrees C accompanied by at least one respiratory and at least one 
systemic symptom).
RESULTS: In the two studies combined, the risk of influenza among subjects 
assigned to either once-daily or twice-daily oseltamivir (1.2 percent and 1.3 
percent, respectively) was lower than that among subjects assigned to placebo 
(4.8 percent; P<0.001 and P=0.001 for the comparison with once-daily and 
twice-daily oseltamivir, respectively). The protective efficacy of oseltamivir 
in the two active-treatment groups combined was 74 percent (95 percent 
confidence interval, 53 to 88 percent) at all the sites combined and 82 percent 
(95 percent confidence interval, 60 to 93 percent) at sites in Virginia, where 
the rate of influenza infection was higher than the overall rate. For 
culture-proved influenza, the rate of protective efficacy in the two oseltamivir 
groups combined was 87 percent (95 percent confidence interval, 65 to 96 
percent). The rate of laboratory-confirmed influenza infection was lower with 
oseltamivir than with placebo (5.3 percent vs. 10.6 percent, P<0.001). 
Oseltamivir was well tolerated but was associated with a greater frequency of 
nausea (12.1 percent and 14.6 percent in the once-daily and twice-daily groups, 
respectively) and vomiting (2.5 percent and 2.7 percent, respectively) than was 
placebo (nausea, 7.1 percent; vomiting, 0.8 percent). However, the frequency of 
premature discontinuation of drug or placebo was similar among the three groups 
(3.1 to 4.0 percent).
CONCLUSIONS: Oseltamivir administered daily for six weeks by the oral route is 
safe and effective for the prevention of influenza.