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- Title
COVID-19 Rebound After VV116 vs Nirmatrelvir-Ritonavir Treatment: A Randomized Clinical Trial.
- Authors
Yang, Zhitao; Xu, Yu; Zheng, Ruizhi; Ye, Lei; Lv, Gang; Cao, Zhujun; Han, Rulai; Li, Mian; Zhu, Yuanyue; Cao, Qiuyu; Ding, Yi; Wang, Jiqiu; Tan, Yun; Liu, Feng; Wei, Dong; Tan, Wei; Jiang, Weiwei; Sun, Jing; Sun, Shouyue; Shao, Jie
- Abstract
Key Points: Question: How common is COVID-19 rebound after a standard 5-day course of treatment with VV116 vs nirmatrelvir-ritonavir? Findings: In this randomized clinical trial of 345 patients with mild-to-moderate COVID-19, viral load rebound occurred in 20.0% of patients in the VV116 group and 21.7% of patients in the nirmatrelvir-ritonavir group. Symptom rebound occurred in 25.6% of patients in the VV116 group and 24.5% of patients in the nirmatrelvir-ritonavir group. Meaning: Viral load rebound and symptom rebound are both common and not significantly different after a standard 5-day course of treatment with either VV116 or nirmatrelvir-ritonavir for mild-to-moderate COVID-19. Importance: With the widespread use of anti–SARS-CoV-2 drugs, accumulating data have revealed potential viral load rebound after treatment. Objective: To compare COVID-19 rebound after a standard 5-day course of antiviral treatment with VV116 vs nirmatrelvir-ritonavir. Design, Setting, and Participants: This is a single-center, investigator-blinded, randomized clinical trial conducted in Shanghai, China. Adult patients with mild-to-moderate COVID-19 and within 5 days of SARS-CoV-2 infection were enrolled between December 20, 2022, and January 19, 2023, and randomly allocated to receive either VV116 or nirmatrelvir-ritonavir. Interventions: Participants in the VV116 treatment group received oral 600-mg VV116 tablets every 12 hours on day 1 and 300 mg every 12 hours on days 2 through 5. Participants in the nirmatrelvir-ritonavir treatment group received oral nirmatrelvir-ritonavir tablets with 300 mg of nirmatrelvir plus 100 mg of ritonavir every 12 hours for 5 days. Participants were followed up every other day until day 28 and every week until day 60. Main Outcomes and Measures: The primary outcome was viral load rebound (VLR), defined as a half-log increase in viral RNA copies per milliliter compared with treatment completion. Secondary outcomes included a reduction in the cycle threshold value of 1.5 or more, time until VLR, and symptom rebound, defined as an increase of more than 2 points in symptom score compared with treatment completion. The primary outcome and secondary outcomes were analyzed using the full analysis set. Sensitivity analyses were conducted using the per protocol set. Adverse events were analyzed using the safety analysis set. Results: The full analysis set included 345 participants (mean [SD] age, 53.2 [16.8] years; 175 [50.7%] were men) who received VV116 (n = 165) or nirmatrelvir-ritonavir (n = 180). Viral load rebound occurred in 33 patients (20.0%) in the VV116 group and 39 patients (21.7%) in the nirmatrelvir-ritonavir group (P =.70). Symptom rebound occurred in 41 of 160 patients (25.6%) in the VV116 group and 40 of 163 patients (24.5%) in the nirmatrelvir-ritonavir group (P =.82). Viral whole-genome sequencing of 24 rebound cases revealed the same lineage at baseline and at viral load rebound in each case. Conclusions and Relevance: In this randomized clinical trial of patients with mild-to-moderate COVID-19, viral load rebound and symptom rebound were both common after a standard 5-day course of treatment with either VV116 or nirmatrelvir-ritonavir. Prolongation of treatment duration might be investigated to reduce COVID-19 rebound. Trial Registration: Chinese Clinical Trial Registry Identifier: ChiCTR2200066811 This randomized clinical trial compares COVID-19 rebound after a standard 5-day course of antiviral treatment with VV116 vs nirmatrelvir-ritonavir.
- Subjects
CHINA; COMBINATION drug therapy; RISK assessment; DIARRHEA; VIRAL load; RESEARCH funding; DATA analysis; STATISTICAL sampling; HOSPITAL care; RANDOMIZED controlled trials; SEVERITY of illness index; REVERSE transcriptase polymerase chain reaction; CHI-squared test; DESCRIPTIVE statistics; AGE distribution; ANTIVIRAL agents; LONGITUDINAL method; KAPLAN-Meier estimator; ODDS ratio; DRUG efficacy; STATISTICS; RITONAVIR; DISEASE relapse; COMPARATIVE studies; CONFIDENCE intervals; VOMITING; COVID-19; SEQUENCE analysis; PROPORTIONAL hazards models; NAUSEA; DISEASE risk factors
- Publication
JAMA Network Open, 2024, Vol 7, Issue 3, pe241765
- ISSN
2574-3805
- Publication type
Article
- DOI
10.1001/jamanetworkopen.2024.1765