Yan Jiayi, Cai Hong, Wang Jieying, Zhu Mingli, Li Ping, Li Peiying, Wu Bin, Che Xiajing, Gu Leyi, Mou Shan
Department of Nephrology, Molecular Cell Lab for Kidney Disease, Shanghai Peritoneal Dialysis Research Center, Ren Ji Hospital, Uremia Diagnosis and Treatment Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Academy of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Front Pharmacol. 2023 Mar 22;14:1147980. doi: 10.3389/fphar.2023.1147980. eCollection 2023.
Nirmatrelvir/ritonavir has demonstrated effectiveness in high-risk patients with coronavirus disease 2019 (COVID-19). However, investigations on the efficacy and safety of nirmatrelvir/ritonavir in patients with kidney dysfunction are limited. Data were collected from the patients admitted to a COVID-19 referral center in Shanghai, China. Patients were at least 18 years of age and had a baseline estimated glomerular filtration rate (eGFR) of <60 ml/min/1·73 m. The primary endpoint was a composite of all-cause mortality, intensive care unit admission, or cardiovascular events. The secondary endpoint was viral shedding. Among the 195 participants, 73 received nirmatrelvir/ritonavir. A lower risk of the primary endpoint was observed in nirmatrelvir/ritonavir recipients compared with non-recipients [adjusted HR 0.56 (95% CI: 0.32-0.96); 0.035]. Nirmatrelvir/ritonavir recipients experienced a shorter duration of viral shedding [adjusted HR 3·70 (95%CI: 2.60-5.28); < 0.001) and faster viral load clearance versus non-recipients. Among the nirmatrelvir/ritonavir users, earlier initiation of nirmatrelvir/ritonavir within 5 days since COVID-19 diagnosis was related with shorter viral shedding time (adjusted HR 7.84 [95% CI: 3.28-18.76]; < 0.001) compared to late initiation. No patients reported serious adverse events during treatment. Our findings support the early initiation of nirmatrelvir/ritonavir for high-risk patients with impaired kidney function. This could improve patient outcomes and shorten the viral shedding period.
奈玛特韦/利托那韦已在2019冠状病毒病（COVID-19）高危患者中显示出有效性。然而，关于奈玛特韦/利托那韦在肾功能不全患者中的疗效和安全性的研究有限。数据收集自中国上海一家COVID-19转诊中心收治的患者。患者年龄至少18岁，基线估计肾小球滤过率（eGFR）<60 ml/min/1·73 m²。主要终点是全因死亡率、重症监护病房入院或心血管事件的复合终点。次要终点是病毒脱落。在195名参与者中，73人接受了奈玛特韦/利托那韦。与未接受者相比，接受奈玛特韦/利托那韦的患者发生主要终点的风险较低[调整后风险比0.56（95%置信区间：0.32-0.96）；P=0.035]。接受奈玛特韦/利托那韦的患者病毒脱落持续时间较短[调整后风险比3.70（95%置信区间：2.60-5.28）；P<0.001]，与未接受者相比病毒载量清除更快。在使用奈玛特韦/利托那韦的患者中，与延迟用药相比，在COVID-19诊断后5天内更早开始使用奈玛特韦/利托那韦与较短的病毒脱落时间相关（调整后风险比7.84[95%置信区间：3.28-18.76]；P<0.001）。治疗期间没有患者报告严重不良事件。我们的研究结果支持对肾功能受损的高危患者尽早开始使用奈玛特韦/利托那韦。这可以改善患者预后并缩短病毒脱落期。
