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F. Khawaja et al.
good, regardless of prandial state.98 Although clinical trials on RSV infections in transplant recipients have been chal- lenging due to low recruitment,71 two phase II trials on presatovir in HCT recipients with RSV infections were recently completed99,100 (ClinicalTrials.gov number NCT02254408). To overcome potential low recruitment, 189 HCT recipients with RSV infections limited to the upper respiratory tract were recruited from a total of 43 centers in nine countries over 2.5 years.99,100 Preliminary data showed that presatovir was not effective at reducing nasal RSV viral load over time or at reducing the incidence of lower respiratory tract complications. However, in an exploratory analysis, presatovir did reduce the rate of pro- gression to lower respiratory tract complications in patients with lymphopenia relative to the rate in placebo- treated patients. Furthermore, presatovir was not effective at reducing nasal RSV viral load, supplemental oxygen use or all-cause mortality in another phase II trial in HCT recipients with RSV LRTI.99,100 Several lessons were learned from the two trials. HCT recipients with one or more risk factors (i.e. lymphopenia, neutropenia, or infected within a year from transplant) for poorer outcomes from RSV infections may benefit the most from an effective antiviral therapy. On the other hand, time from symptom onset and time before the development of lower respiratory tract complications are probably critical factors in deter- mining the effectiveness of fusion inhibitors.
The development of another novel agent, ALX-0171, was recently stopped and the drug may not enter clinical trials on RSV infections in HCT recipients. This inhaled agent is a trivalent nanobody that inhibits RSV replication by binding the F-protein on the surface of the virus and thereby neutralizes RSV by blocking virus uptake into cells. A recent phase 1 trial in infants with RSV infections was prematurely terminated due to lack of efficacy (ClinicalTrials.gov identifier: NCT03418571).
Prevention of respiratory syncytial virus infection
The prevention of RSV in HM patients and HCT recipi- ents is limited to infection control measures and interven- tions. There are many reports of outbreaks in these popu-
lations of patients,13-18,101,102 and the emphasis has been on multifaceted interventions, including compliance with hand hygiene, contact precautions with gowns and the use of gloves, screening visitors and healthcare workers for respiratory symptoms and restricting visitors and healthcare workers if they are symptomatic, grouping RSV-infected patients together, and sometimes screening asymptomatic patients in the same treatment areas. These interventions have been shown to be effective in mixed adult and pediatric patients.19,103,104 At our institution, we place all patients diagnosed with respiratory viral infec- tions on contact and droplet precautions.105
Interestingly, the use of chemoprophylaxis with palivizumab was described during an outbreak15 in patients who were at high risk of acquiring RSV infections in a bone marrow transplant ward. Sixteen asymptomatic patients were given one prophylactic dose of palivizumab during the outbreak, and none developed an RSV infec- tion. These results warrant further investigation into the use of palivizumab in an outbreak; however, no definite recommendation can be made at this time. Finally, an RSV vaccine for children or adults is not available at present. Multiple trials in children and healthy adults are in progress (www: ClinicalTrials.gov). Whether immunization for RSV would be beneficial in immunocompromised patients is uncertain.
Conclusions
RSV is a common respiratory viral infection in adult HM patients and HCT recipients. Its incidence is affected by its seasonality and geography and the diagnostic method used. The mortality rate associated with RSV can be high in severely immunocompromised patients with LRTI. The use of an ISI is helpful to stratify HCT recipients into risk categories; a similar scoring system is needed for HM patients. Ribavirin, with or without IVIG, may mitigate the impact of RSV infections in this population of patients. The further development of new antiviral agents or other treatment modalities is of the utmost importance to have a greater impact on rates of progression to LTRI and mor- tality in adult HM patients and HCT recipients.
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