Patients who report use of nirmatrelvir-ritonavir during acute COVID-19 infection have fewer symptoms and lower viral loads, but nirmatrelvir-ritonavir receipt is associated with increased risk for symptom and viral rebound when compared with no treatment. These study results were presented at IDWeek 2023, held from October 11 to 15, in Boston, Massachusetts. 

Researchers conducted an analysis among patients who tested positive for SAR-CoV-2 infection between March 2022 and March 2023. The researchers compared symptom and viral load trajectories during acute COVID-19 infection between patients who received nirmatrelvir-ritonavir and those who received no treatment. Patients were enrolled within 6 days of symptom onset; the follow-up period was 10 days. The researchers collected data on patient demographics, daily symptoms, medication history, and clinical history. Specimens were also collected from the patients for SARS-CoV-2 testing via quantitative polymerase chain reaction. The researchers used propensity score matching balance covariates between nirmatrelvir-ritonavir recipients and those who received no treatment.

The researchers evaluated patients for the occurrence of symptom and viral rebound. Symptom rebound was as defined as the occurrence of at least 2 additional symptoms; viral rebound was defined as an increase of at least 0.5 over a minimum of 5 log10 IU/mL in SARS-CoV-2 viral load. Wilcoxon testing was used to compare mean daily symptoms and viral loads between the groups, and logistic regression was used to calculate the odds of rebound. 

After propensity score matching, the final analysis included 116 patients in the treated group and 232 in the untreated group. The median patient age ranged between 54 and 56 years, 83% of patients were non-Hispanic White, 91% had received at least 3 COVID-19 vaccine doses, 78% reported comorbidities, and 28% reported prior COVID-19 infection.

In outpatient settings, N/R treated individuals had fewer symptoms and lower viral loads, but greater odds of symptom and viral rebound compared to similar untreated individuals.

The median time between symptom onset and nirmatrelvir-ritonavir initiation was 2 (IQR, 1-3 days). 

Overall, the rate of symptom rebound was higher among patients in the treated vs untreated group (32% vs 19%; odds ratio [OR], 1.95; 95% CI, 1.17-3.24).

However, the number of mean daily symptoms were lower in patients who received nirmatrelvir-ritonavir vs no treatment (1.6 vs 2.0; P =.2). Of note, the reduction in mean daily symptoms associated with nirmatrelvir-ritonavir use was significant when the analysis was restricted to patients who experienced no symptom rebound (0.8 vs 1.5; P =.01).

Viral load rebound was observed in 25% of patients who received nirmatrelvir-ritonavir and 13% of those who received no treatment (OR, 2.31; 95% CI, 1.17-4.55). However, further between-group analyses showed significantly lower mean daily viral loads in nirmatrelvir-ritonavir recipients overall (1.5 vs 2.7 log10 IU/mL). Similar results were observed in nirmatrelvir-ritonavir recipients with (4.8 vs 5.6 log10 IU/mL) and without (1.1 vs 2.5 log10 IU/mL) incident viral rebound (all P <.05).

Limitations of this study include the use of different specimen types (nasal vs saliva swabs) and the use of different quantification standards to assess SARS-CoV-2 viral load. 

According to the researchers, “In outpatient settings, N/R [nirmatrelvir-ritonavir] treated individuals had fewer symptoms and lower viral loads, but greater odds of symptom and viral rebound compared to similar untreated individuals.”

This article originally appeared on Infectious Disease Advisor.

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