Paxlovid Effectiveness Extends to New Omicron Subvariants

A “real-world” assessment of the effectiveness of the antiviral combination of nirmatrelvir-ritonavir in reducing risk of hospitalization from severe COVID-19 finds that protection against BA4 and BA5 omicron subvariants is similar to that demonstrated in the regulatory approval trials with delta and pre-delta subvariants.

“Given the epidemiological shift in circulating variants, a suggestion of a rebound phenomenon, and extensive vaccination of individuals at high risk, real-world data are crucial to evaluate the impact of nirmatrelvir-ritonavir and other therapies targeting COVID-19 to inform ongoing policy and practice decisions,” the investigators explained.

Neil Aggarwal, MD, Department of Medicine, University of Colorado School of Medicine, Aurora, CO, and colleagues characterize the propensity-matched, retrospective, observational cohort study as the first to examine the effectiveness of the antiviral against the currently circulating BA4 and BA5.

The investigators used records from a statewide health system in Colorado to compare outcomes of 7168 propensity matched outpatients with COVID-19 treated with nirmatrelvir-ritonavir to the course of 9361 who did not receive the antiviral, in the period between March 26 and August 25, 2022.

Emergency department visits after the diagnosis and treatment served as a surrogate for clinical important relapse. Although a test for SARS-CoV-2 was not often in the medical record, a positive test result was required for the antiviral to be prescribed and so assumed to have been obtained at home.

Aggarwal and colleagues reported that the antiviral treatment was associated with reduced 28-day all-cause hospitalization compared to no treatment (0.9% vs 1.4%, adjusted odds ratio [OR] 0.45, 95%CI 0.33-0.62). In addition, treatment was associated with significantly lower 28-day all-cause mortality (≤0.1% vs 0.2%, OR 0.15 [0.03-0.50]). In the subset of patients who were hospitalized, receiving the antiviral treatment prior to admission was associated with a shorter mean hospital length of stay of 3.4 days (SD 3.9) compared to 5.2 days (7.9) in those who had not received the antiviral as outpatients.

The investigators noted that although the antiviral was effective, the treatment effect was somewhat less than with delta and pre-delta subvariants; which they attributed to several possible factors.

“Waning COVID-19 severity, increased vaccination rates, varying time to treatment initiation after symptom onset, and presumed lower adherence to the prescribed 5-day regimen in a real world-study might explain the reduced nirmatrelvir-ritonavir effectiveness in our study compared with the pivotal EPIC-HR trial,” Aggarwal and colleagues opined.

In accompanying commentary, Carlos KH Wong, PhD and Kristy TK Lau, MSc, Department of Pharmacology and Pharmacy, and Gabriel M Leung, MD, MPH, WHO Collaborating Centre for Infectious Disease Epidemiology and Control, School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, China, suggest that that the reduced odds of emergency department visits not only reflects treatment effectiveness, but also a low incidence of clinically significant rebound after the antiviral.

The commentators point out, however, that effectiveness against current variants is not an indication of protection from future forms. "At the time of writing, emerging and recombinant variants of omicron continue to pose an imminent threat to public health, especially XBB15 and BQ11, which have even greater immune evasion capabilities than BA5,” they warn.