Ziresovir in hospitalised infants with RSV infection

Read article: Submitted by: Robert Duguid, Royal Darwin Hospital, September 2024 .Supervising consultants: Jennifer Yan, Joshua Francis, Te-Yu Hung.Background:Respiratory syncytial virus (RSV) is a leading cause of hospitalisation of infants globally. Notwithstanding improvements in supportive care measures, many decades have passed with little progress in the development of effective anti-viral therapeutics that can reduce RSV related morbidity. However, there has been a recent surge of promising interventions including maternal vaccines and infant immunisation that have created justifiable excitement amongst paediatricians. Ziresovir is an orally administered RSV F protein inhibitor developed to treat RSV infection. Findings:In this pharmaceutical company sponsored phase 3 multicentre, double-blind, randomised, placebo-control trial of 302 Chinese infants aged 1-24 months hospitalised with RSV infection; infants who received ziresovir twice daily for 5 days had statistically significant reduction in Wang clinical bronchiolitis score at day 3 compared to placebo (-3.4 points [95% CI, -3.7 to -3.1] vs. -2.7 points [95% CI, -3.1 to -2.2], -0.8 points [95% CI, -1.3 to -0.3]; p=0.002). There was also a greater reduction in viral load in the ziresovir group without significant adverse events associated with its use. Take home message:This is a well conducted placebo-controlled therapeutics clinical trial in children targeting an important disease in an appropriate population. However, the clinical significance of the primary outcome chosen is questionable. Given the majority of infants in high-income settings (even those at the highest risk of severe RSV infection) will improve with supportive care, outcomes such as duration of hospitalisation and ICU admission would be of greater importance to this cohort. It would be interesting to see ziresovir (and other novel RSV strategies) studied in low- and middle-income settings where mortality and morbidity related to RSV infection is far greater. It is also notable that anti-viral resistance developed in 9% of patients during treatment.