We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Optimal timing of nirmatrelvir/ritonavir treatment after COVID-19 symptom onset or diagnosis: target trial emulation.
- Authors
Wong, Carlos K. H.; Lau, Jonathan J.; Au, Ivan C. H.; Lau, Kristy T. K.; Hung, Ivan F. N.; Peiris, Malik; Leung, Gabriel M.; Wu, Joseph T.
- Abstract
Reports of symptomatic rebound and/or test re-positivity among COVID-19 patients following the standard five-day treatment course of nirmatrelvir/ritonavir have sparked debates regarding optimal treatment timing and dosage. It is unclear whether initiating nirmatrelvir/ritonavir immediately after symptom onset would improve clinical outcomes and/or lead to post-treatment viral burden rebound due to inadequate viral clearance during treatment. Here we show that, by emulating a randomized target trial using real-world electronic medical record data from all 87,070 adult users of nirmatrelvir/ritonavir in Hong Kong between 16th March 2022 and 15th January 2023, early initiation of nirmatrelvir/ritonavir treatment (0 to 1 days after symptom onset or diagnosis) significantly reduced the incidence of 28-day all-cause mortality and hospitalization compared to delayed initiation (2 or more days) (absolute risk reduction [ARR]: 1.50% (95% confidence interval 1.17-1.80%); relative risk [RR]: 0.77 (0.73, 0.82)), but may be associated with a significant elevated risk of viral burden rebound (ARR: −1.08% (−1.55%, −0.46%)), although the latter estimates were associated with high uncertainty due to limited sample sizes. As such, patients should continue to initiate nirmatrelvir/ritonavir early after symptom onset or diagnosis to better protect against the more serious outcomes of hospitalization and mortality. Nirmatrelvir/ritonavir can reduce COVID-19 severity when initiated within five days of symptom onset but the optimal timing within this window is unknown. Here, the authors emulate a randomised trial using electronic health records from Hong Kong and find evidence for a benefit of early treatment initiation.
- Subjects
HONG Kong (China); COVID-19 treatment; RITONAVIR; ELECTRONIC health records; COVID-19; SYMPTOMS
- Publication
Nature Communications, 2023, Vol 14, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-023-43706-0