Modified-dose nirmatrelvir-ritonavir well tolerated, effective in advanced CKD patients

Modified-dose regimens of nirmatrelvir-ritonavir are well tolerated and effective in COVID-19 patients with advanced chronic kidney disease (CKD), including those on dialysis, a study by the Chinese University of Hong Kong (CUHK) has shown.

Nirmatrelvir-ritonavir is currently not recommended in patients with estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m². However, patients with advanced CKD, especially those on dialysis, are at increased risk of severe COVID-19. Researchers from CUHK therefore evaluated the safety profile (primary outcome) as well as clinical and virological outcomes of nirmatrelvir-ritonavir used at doses modified according to eGFR in CKD patients with COVID-10. [Clin Infect Dis 2023;doi:10.1093/cid/ciad371]

The prospective, single-arm, interventional study included 85 patients (mean age, 64.2 years; male, 58.8 percent; vaccinated with ≥3 doses of COVID-19 vaccine, 88.2 percent) recruited between November 2022 and January 2023. Among these patients, 59 (69.4 percent) had stage 5 CKD and were on dialysis, six (7.1 percent) had eGFR <30 mL/min/1.73 m² and were not on dialysis, 10 (11.8 percent) had eGFR 30–60 mL/min/1.73 m², and 10 patients (11.8 percent) had eGFR >60 mL/min/1.73 m² (ie, controls).

Patients in the control group received nirmatrelvir 300 mg and ritonavir 100 mg BID for 5 days. Those with 30–60 mL/min/1.73 m² received nirmatrelvir 150 mg and ritonavir 100 mg BID for 5 days, while those with eGFR <30 mL/min/1.73 m² who were not on dialysis received nirmatrelvir 300 mg and ritonavir 100 mg QD on day 1 followed by nirmatrelvir 150 mg and ritonavir 100 mg QD on days 2–5.

In patients on dialysis, those with body weight ≥40 kg received nirmatrelvir 300 mg and ritonavir 100 mg QD on day 1 followed by nirmatrelvir 150 mg and ritonavir 100 mg QD on days 2–5. Patients on dialysis with body weight <40 kg received nirmatrelvir 150 mg and ritonavir 100 mg QD on day 1, followed by nirmatrelvir 150 mg and ritonavir 100 mg QD every 48 hours on days 2–5. Patients on haemodialysis (n=39) took nirmatrelvir-ritonavir after the haemodialysis procedure.

Almost all patients (n=80; 94.1 percent) completed the full course of oral antiviral treatment. Adverse events (AEs) and serious AEs (SAEs) occurred in 9.4 percent and 5.9 percent of patients, respectively, and led to drug discontinuation in 5.9 percent of patients.

Rates of AEs and SAEs were comparable between patients with eGFR <30 mL/min/1.73 m² and >30 mL/min/1.73 m² (AEs, 9.2 percent and 10 percent, respectively) (SAEs, 6.2 percent and 5 percent, respectively). Drug discontinuation due to AEs occurred in 7.7 percent of patients with eGFR <30 mL/min/1.73 m² and none of the patients with eGFR >30 mL/min/1.73 m².

Viral load significantly decreased on days 5, 15 and 30 (p<0.001), and the reduction was consistent among patients with eGFR <30 mL/min/1.73 m². By day 5, 63.8 percent of patients had a polymerase chain reaction (PCR) cycle threshold (Ct) value >30.

Although 11.8 percent of patients experienced virological rebound, this was transient and asymptomatic. Symptomatic rebound occurred in 5.9 percent of patients at a mean of 4 days after symptom resolution. Most symptoms were runny nose, cough, dry mouth, and myalgia, which were transient and not associated with virological rebound.

“Our results provide supportive evidence of nirmatrelvir-ritonavir use in patients with eGFR <30 mL/min/1.73 m², including those on dialysis,” the researchers concluded. “Based on our preliminary data, modified doses of nirmatrelvir-ritonavir can be considered in this high-risk group of patients with advanced CKD, especially when an alternative treatment is unavailable.”