The antiviral drug combination nirmatrelvir–ritonavir (Paxlovid) was estimated to be 54% effective against SARS-CoV-2 Omicron BA.2, BA.4, and BA.5 hospitalization or death but was 80% when taken within 5 days of symptom onset, according to an observational study published yesterday in The Lancet Infectious Diseases.
Paxlovid, an oral drug, is authorized for the treatment of COVID-19 patients aged 12 years and older at high risk for severe illness.
Researchers from the University of California at Berkeley and Paxlovid maker Pfizer led an analysis of the electronic health records of nonhospitalized patients aged 12 and older who tested positive for COVID-19 from April 8 to October 7, 2022, at Kaiser Permanente Southern California. Overall, 86% had received at least two doses of COVID-19 vaccine, and 61% had received at least three.
The study generated the first observational data that included the timing of symptom onset. A total of 12,574 patients received Paxlovid at any time during their illness, 10,038 Paxlovid recipients were tested within 5 days of symptom onset, 1,755 were tested after that timeframe, and 781 didn't have COVID-19 symptoms at the point of testing.
90% effective when given on day of test
Hospitalization or death within 30 days occurred in 51 (0.7%) of Paxlovid recipients and 695 (0.6%) nonrecipients. Paxlovid's estimated effectiveness in preventing hospitalization or death was 53.6% (95% confidence interval [CI], 6.6% to 77.0%). Effectiveness rose to 79.6% (95% CI, 33.9% to 93.8%) when Paxlovid was received within 5 days of symptom onset.
Among patients who were tested within 5 days of symptom onset and received Paxlovid on the day of the test, estimated effectiveness increased to 89.6% (95% CI, 50.2% to 97.8%). Effectiveness fell to 44% among patients given Paxlovid 6 or more days after symptom onset and those who didn't have COVID-19 symptoms.
The authors said the findings show the benefit of early Paxlovid treatment among patients with mild to moderate COVID-19, regardless of vaccination status or age. "These findings are even more notable because in this population with high levels of vaccination, we still see additional benefits of this treatment," senior author Sara Tartof, PhD, of Kaiser Permanente, said in a Kaiser news release.
Among patients who were tested within 5 days of symptom onset and received Paxlovid on the day of the test, estimated effectiveness increased to 89.6%
Tartof noted that Paxlovid is most effective when given soon after symptom onset. "However, there is still some benefit to treatment 6 or more days after symptom onset," she said. "People should talk with their doctors about the best approach for them."
Absolute benefits may be low
In a related commentary, Kyle Molina, PharmD, and Adit Ginde, MD, both of Scripps Health, said the low rate of hospitalization and death by 30 days among untreated patients may limit the absolute treatment benefits in a highly vaccinated population infected with Omicron, with the need to treat 100 to 200 patients to prevent one hospitalization or death.
"Studies of whether nirmatrelvir–ritonavir affects additional patient-centred outcomes, such as post-COVID-19 condition (also known as long COVID), are planned and could affect the cost-effectiveness of the intervention and whether continued widespread use is merited as the pandemic evolves," they wrote. "Characterisation of patients who most benefit from treatment with nirmatrelvir–ritonavir and studies of when treatment is most effective are needed."
