Insights from Investigator Evaluating Paxlovid's Effectiveness in Vaccinated Older Adults

Randomized clinical trials of nirmatrelvir-ritonavir (Paxlovid) have shown reduced COVID-19-related hospitalizations in unvaccinated individuals, but its effectiveness in vaccinated populations remains unclear. This question is particularly important for older adults, who are at higher risk for severe COVID-19 outcomes. In an exclusive interview with investigator Katherine L Kahn, MD, professor of Medicine at UCLA, we examined the effects of Paxlovid on older, vaccinated adults.

The study conducted using data from Ontario, Canada, focused on over 1.6 million individuals aged 65-74. The population was highly vaccinated, with nearly 88% having received at least two doses of the COVID-19 vaccine. Participants were analyzed to determine the impact of increased access to Paxlovid on hospitalization and mortality rates. The study’s main goal was to evaluate if the positive outcomes observed in unvaccinated populations from previous trials applied to vaccinated older adults.

In Ontario, access to Paxlovid was restricted based on age and risk factors. Individuals aged 70 and older could access the medication if they tested positive for COVID-19 and had at least one symptom. For those under 70, only high-risk individuals could receive Paxlovid. This policy allowed for a unique opportunity to evaluate how restricted access to the medication affected a highly vaccinated population.

The findings showed that increasing access to Paxlovid for older individuals did not significantly improve hospitalization or death rates. Kahn explained, “Doubling the access to Paxlovid for older individuals didn’t significantly improve hospitalization or death rates, which raised questions about whether Paxlovid should be used routinely in vaccinated, standard-risk individuals.”

The study challenges the routine use of Paxlovid in vaccinated populations. Previous trials have shown that Paxlovid reduces hospitalization and death rates in unvaccinated individuals, but Kahn’s study suggests that for vaccinated, standard-risk individuals, the medication may not offer the same benefits. “These results challenge the effectiveness of Paxlovid in the highly vaccinated population,” Kahn stated.

Given the high vaccination rates, the study implies that vaccination itself significantly reduces the likelihood of severe COVID-19 outcomes, making the need for treatments like Paxlovid less critical for vaccinated individuals. The study calls into question whether the high costs and potential side effects of Paxlovid are justified for vaccinated individuals, particularly those at standard risk.

Kahn’s research highlights the need for ongoing investigation into the effectiveness of COVID-19 treatments in vaccinated populations. A recent CDC report found a 30% reduction in hospitalization rates for those vaccinated against COVID-19, with rates improving further for individuals over 65 and for those with high-risk conditions. For these groups, hospitalization reductions were observed at rates of 40% and up to 55%, respectively.

Kahn emphasized the importance of shared decision-making in treatment protocols. “We should consider linking vaccination and the use of Paxlovid in future treatment guidelines,” Kahn said. “The more highly vaccinated a population is, the less likely they are to develop COVID, which reduces the need for treatments like Paxlovid.” Although, she also noted that for those who do get COVID, “we should consider whether they are willing to use a medicine that might cause side effects, such as a bad taste or rebound symptoms.”

The cost of Paxlovid is another key factor in its accessibility. Kahn highlighted that the average cost of a 5-day treatment course of Paxlovid is $1,669.43, raising questions about the cost-effectiveness of widespread use in vaccinated individuals.

This study provides valuable data for clinicians and policymakers as they navigate COVID-19 treatment in vaccinated populations. The findings suggest that Paxlovid may not be as beneficial in reducing hospitalizations or deaths for vaccinated, standard-risk older adults, challenging its routine use for these groups. The study also emphasizes the importance of clear communication between healthcare providers and patients, as well as the need for an integrated approach to vaccination and treatment decisions.

As Kahn concluded, “The more we can educate and engage patients in decision-making, the better equipped we’ll be to manage COVID-19 effectively, particularly in vaccinated, older populations.”

Reference
Mafi JN, Vangala S, Kapral MK, et al. Hospitalizations and Mortality Among Older Adults With and Without Restricted Access to Nirmatrelvir-Ritonavir. JAMA. Published online February 20, 2025. doi:10.1001/jama.2024.28099