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. 2022 Dec 1;5(12):e2245086.
doi: 10.1001/jamanetworkopen.2022.45086.

Incidence of Viral Rebound After Treatment With Nirmatrelvir-Ritonavir and Molnupiravir

Grace Lai-Hung Wong  1   2   3 , Terry Cheuk-Fung Yip  1   2   3 , Mandy Sze-Man Lai  1   2   3 , Vincent Wai-Sun Wong  1   2   3 , David Shu-Cheong Hui  1   2   4 , Grace Chung-Yan Lui  1   2   4
Affiliations

Incidence of Viral Rebound After Treatment With Nirmatrelvir-Ritonavir and Molnupiravir

Grace Lai-Hung Wong et al. JAMA Netw Open. .

Abstract

Importance: Some patients treated with nirmatrelvir-ritonavir have experienced rebound of COVID-19 infections and symptoms; however, data are scarce on whether viral rebound also occurs in patients with COVID-19 receiving or not receiving molnupiravir.

Objective: To examine the incidence of viral rebound in patients with COVID-19 who were treated with the oral antiviral agents nirmatrelvir-ritonavir and molnupiravir.

Design, setting, and participants: This cohort study identified 41 255 patients with COVID-19 who were hospitalized from January 1, 2022, to March 31, 2022, in Hong Kong and assessed 12 629 patients with serial cycle threshold (Ct) values measured. Patients were followed up until the occurrence of the clinical end point of interest, death, date of data retrieval (July 31, 2022), or up to 30 days of follow-up, whichever came first.

Exposures: Molnupiravir or nirmatrelvir-ritonavir treatment.

Main outcomes and measures: Viral rebound, defined as a Ct value greater than 40 that decreased to 40 or less.

Results: Of 12 629 patients (mean [SD] age, 65.4 [20.9] years; 6624 [52.5%] male), 11 688 (92.5%) were oral antiviral nonusers, 746 (5.9%) were molnupiravir users, and 195 (1.5%) were nirmatrelvir-ritonavir users. Compared with nonusers, oral antiviral users were older, had more comorbidities, and had lower complete vaccination rates. The mean (SD) baseline Ct value was slightly higher in nirmatrelvir-ritonavir users (22.2 [6.0]) than nonusers (21.0 [5.4]) and molnupiravir users (20.9 [5.4]) (P = .04). Viral rebound occurred in 68 nonusers (0.6%), 2 nirmatrelvir-ritonavir users (1.0%), and 6 molnupiravir users (0.8%). Among 76 patients with viral rebound, 12 of 68 nonusers, 1 of 6 molnupiravir users, and neither of the nirmatrelvir-ritonavir users died of COVID-19.

Conclusions and relevance: In this cohort study, viral rebound was uncommon in patients taking molnupiravir or nirmatrelvir-ritonavir and was not associated with increased risk of mortality. Given these findings, novel oral antivirals should be considered as a treatment for more patients with COVID-19 in the early phase of the infection.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr G.L.-H. Wong reported receiving grants from Gilead Sciences and personal fees from Abbott, AbbVie, Bristol-Myers Squibb, Echosens, Furui, Gilead Sciences, Janssen, and Roche outside the submitted work. Dr Yip reported serving as a speaker and consultant for Gilead Sciences outside the submitted work. Dr V.W.-S. Wong reported receiving personal fees from Abbott, AbbVie, Boehringer Ingelheim, Echosens, Gilead Sciences, Intercept, Inventiva, Novo Nordisk, Pfizer, and TARGET PharmaSolutions and grants from Gilead Sciences outside the submitted work. Dr Lui reported receiving grants from Gilead Sciences, MSD, and ViiV outside the submitted work. No other disclosures were reported.

Figures

Figure.
Figure.. Virologic and Treatment Course of Individuals With Viral Rebound of COVID-19 After Treatment With Molnupiravir or Nirmatrelvir-Ritonavir
The width of the bars corresponds to the length of time each patient received treatment. Ct indicates cycle threshold.
See this image and copyright information in PMC

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