International Society for antiviral research

Developing treatment and prevention strategies for respiratory syncytial virus: Protecting the most vulnerable

John DeVincenzo, MD

Children's Foundation Research Institute at LeBonheur Children's Hospital, Memphis, Tennessee, United States of America

Respiratory syncytial virus (RSV) is the most common cause of infant hospitalization, the most common cause of childhood pneumonia, and rivals influenza in its impact on the frail elderly and other adults with underlying medical conditions. However, there is no licensed vaccine against RSV and the only available therapeutic agent, ribavirin, is cumbersome to deliver, and has limited and controversial efficacy. The only available prevention, palivizumab, is only partially effective, and its use is restricted to young children with underlying medical conditions comprising  <3% of the birth cohort.  There is thus a high unmet medical need for effective RSV antiviral therapies.  Several small molecule experimental antivirals have now been evaluated through early to mid-stage clinical development.  The mechanisms of action of these experimental antivirals include fusion inhibition, nucleoside analogue and non-nucleoside replication inhibition. Administration routes include aerosol and oral delivery.  Several of these antivirals have been evaluated successfully in the RSV human challenge model, and show abilities to safely reduce viral load and concomitantly reduce disease severity in healthy adults when therapy is initiated early after infection detection. These results and their limitations will be discussed and compared. The potential impact of viral resistance will also be discussed.  Translating these findings into successful pivotal clinical trial efficacy results requires a prediction of the therapeutic timing window of efficacy. Various clinical populations have different viral dynamics, and hence likely different therapeutic timing windows. These important differences will be discussed especially relating to predicting future clinical efficacy of much needed RSV antivirals.