Efficacy and safety of oral oseltamivir for influenza prophylaxis in transplant recipients.

BACKGROUND Haematopoietic stem cell transplant (HSCT) and solid organ transplant (SOT) recipients are at high risk for severe influenza and its complications, and may not be adequately protected by vaccination. METHODS Liver, kidney, or liver-kidney transplant or allogeneic HSCT recipients aged ≥1 year were randomized to oseltamivir (75 mg once daily for those ≥13 years or weight-based dosing for children 1-12 years) or placebo for 12 weeks during periods of local influenza circulation. Patients were assessed for influenza infection via daily diary, every-other-week culture and PCR, and baseline and end-of-treatment serology. RESULTS A total of 477 subjects were enrolled (239 oseltamivir and 238 placebo); most were adults (96%) and SOT recipients (81%). In the intent-to-treat population, the frequency of laboratory-confirmed clinical influenza (culture positive and/or >4-fold increase in haemagglutinin antibody inhibition [primary end point]) was similar in the oseltamivir and placebo groups (2.1% [5/237] and 2.9% [7/238]). Incidence of laboratory-confirmed influenza was significantly reduced in the oseltamivir group versus placebo when determined by reverse transcriptase-PCR (1.7% [4/237] versus 8.4% [20/238]; 95% CI 2.8, 11.1) or viral culture (<1% [1/237] versus 3.8% [9/238]; 95% CI 0.7, 6.6), giving protective efficacies of 79.9 and 88.8%, respectively. Serious adverse events (oseltamivir 8% and placebo 10%) and adverse events (oseltamivir 55% and placebo 58%) were reported in both arms with a similar frequency. One illness due to oseltamivir-resistant A/H1N1 virus was detected in each group. CONCLUSIONS Oseltamivir prophylaxis is generally well-tolerated and may reduce culture- or PCR-confirmed influenza incidence in transplant recipients.