Nirmatrelvir-ritonavir therapy demonstrated manageable tolerability among COVID-19 patients with CKD

Despite being an effective oral antiviral therapy for coronavirus 2019 (COVID-19), nirmatrelvir-ritonavir (NMV-r) was not approved for patients with an estimated glomerular filtration rate (eGFR) <30mL/min/1.75m2.1 This can be attributed to a phenomenon known as “renalism”, which is the frequent exclusion of patients with advanced chronic kidney disease (CKD) and patients receiving dialysis and kidney transplant recipients from clinical trials evaluating new drugs.2 Furthermore, pharmacokinetic data implied that levels of nirmatrelvir would accumulate with decreasing kidney function.2 Nevertheless, nephrology experts from the Chinese University of Hong Kong (CUHK)’s Faculty of Medicine (CU Medicine) and the Prince of Wales Hospital (PWH) had suggested that a modified dosage of NMV-r, administered after hemodialysis, can theoretically limit the extent of drug accumulation, allowing the use of this antiviral therapy in patients with CKD.2 However, much remains uncertain in the implementation of NMV-r therapy in patients with CKD.1

A prospective, single-arm interventional study was conducted to evaluate the safety and effectiveness of dose-adjusted NMV-r treatment in patients with CKD and COVID-19.1 A total of 85 adult patients with CKD (eGFR <60mL/min/1.75m2) and COVID-19 infection were recruited.1 Patients with an eGFR <30mL/minute/1.73m2 were classified into the low-eGFR group (n=65), while patients with an eGFR between >30mL/minute/1.73m2 were classified into the high-eGFR group (n=10).1 Additionally, 10 COVID-19 patients with an eGFR >60mL/min/1.75m2 were also included as controls.1 A modified dosage of NMV-r was calculated by the CKD Epidemiology collaboration (CKD-EPI) creatinine equation based on the eGFR of each patient cohort and administered for 5 days.1 The prevalence of adverse events (AEs) and drug-discontinuation events served as the primary endpoints of this study.1 Secondary endpoints focused on the virological outcomes such as polymerase chain reaction (PCR) cycle threshold (Ct) value and virological rebound.1

The modified dose of combined NMV-r therapy has proven to be well-tolerated among COVID-19 patients with CKD.1 The overall prevalence rates of AEs and serious AEs are 9.4% and 5.9%.1 A total of 5 patients discontinued treatment due to severe COVID-19 pneumonia and 2 other patients discontinued from gastrointestinal symptoms.1 No significant difference in the prevalence of AEs was observed between low- and high-eGFR cohorts.1 Cough (21.2%) and fatigue (11.8%) were the 2 most frequent symptoms reported during treatment.1 These symptoms resolved in 18.3 ± 11.1 days with no significant difference in resolution time between the two eGFR cohorts (19.4 ± 11.1 vs. 17.9 ± 11.2; p=0.7).1

In terms of virological outcomes, a negative rapid antigen test (RAT) result was achieved after a mean period of 5.4 ± 3.3 days of treatment.1 The overall mean PCR Ct value was significantly increased after the 5-day treatment when compared to the baseline (p<0.001), with 63.8% of patients having a PCR Ct value >30 by day 5.1 The mean Ct value further increased to 38.8 ± 7.9 at day 15, resulting a final PCR Ct value of 43.7 ± 4.0 at day 30, both of which were significant improvements from the baseline (p<0.001).1 No significant differences in the change in viral load were observed between the low- and high-eGFR cohorts.1 In addition, 11.8% of patients experienced viral rebound during the study period, with 5.9% of patients developed symptom rebound.1 Nevertheless, none of the symptom rebound was associated with viral rebound.1

To conclude, the results of this study provided further evidence supporting the safety profile of NMV-r across different eGFR levels in COVID-19 patients, particularly high-risk patients with CKD (eGFR <30mL/min/1.75m2).1 Additionally, the results also indicated the remarkable efficacy of NMV-r regardless of the patient’s eGFR status.1 Hence, modified doses of NMV-r according to eGFR can be considered for COVID-19 patients with CKD.1

  1. Chan GCK, et al. Safety Profile and Clinical and Virological Outcomes of Nirmatrelvir-Ritonavir Treatment in Patients With Advanced Chronic Kidney Disease and Coronavirus Disease 2019 (COVID-19). Clin Infect Dis. 2023;ciad371.
  2. Hiremath S, et al. Prescribing nirmatrelvir/ritonavir for COVID-19 in advanced CKD. Clin J Am Soc Nephrol. 2022; 17(8):1247-1250.

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