Hospital Ramón y Cajal, IRYCIS, Madrid, Spain.
Instituto de Salud Carlos III Madrid, Madrid, Spain.
J Antimicrob Chemother. 2021 Mar 12;76(4):1046-1050. doi: 10.1093/jac/dkaa547.
Cobicistat, dolutegravir and rilpivirine are all modest inhibitors of proximal tubular creatinine secretion (IPTCrS) and hence a moderate and early non-progressive creatinine estimated glomerular filtration rate (Cr-eGFR) reduction has been observed in clinical trials. Data regarding the impact of combination of those drugs on Cr-eGFR, in the clinical practice, are scarcely known.
Changes in Cr-eGFR after starting darunavir/cobicistat alone or in combination with dolutegravir and/or rilpivirine were studied in a nationwide retrospective cohort study of consecutive HIV-infected patients initiating darunavir/cobicistat. The relationship between Cr-eGFR changes over time and the use of darunavir/cobicistat alone or darunavir/cobicistat plus dolutegravir and/or rilpivirine adjusted by different HIV patient's characteristics, socio-demographics, HIV severity and use of tenofovir concomitant medication other than antiretrovirals was explored through univariate and multivariate analyses.
The analysis included 725 patients. At 48 weeks, the combination of two or more IPTCrS (darunavir/cobicistat with rilpivirine and/or dolutegravir) was associated with higher decreases in Cr-eGFR [adjusted median difference (±SD) -3.5 ± 1.6 (95% CI -6.6 to -0.3), P = 0.047], and a decrease up to or higher than 15 mL/min/1.73 m2 was more frequent [adjusted OR 3.233 (95% CI 1.343-7.782), P = 0.009], with respect to darunavir/cobicistat alone. The Cr-eGFR changes between darunavir/cobicistat and darunavir/cobicistat with rilpivirine and/or dolutegravir showed more significant decreases in patients taking two or more IPTCrS at 12, 24 and 48 weeks. (ClinicalTrials.gov: NCT03042390).
Concomitant use of darunavir/cobicistat plus IPTCrS dolutegravir, rilpivirine, or both produced an additive effect in the expected Cr-eGFR decrease.
考比司他、度鲁特韦和利匹韦林均为近端肾小管肌酐分泌的适度抑制剂（IPTCrS），因此在临床试验中观察到肌酐估计肾小球滤过率（Cr-eGFR）的适度早期非进行性降低。关于这些药物联合使用对 Cr-eGFR 的影响，临床实践中知之甚少。
在一项全国性回顾性队列研究中，对开始使用达芦那韦/考比司他单药或联合度鲁特韦和/或利匹韦林的连续 HIV 感染患者，研究了开始使用达芦那韦/考比司他后 Cr-eGFR 的变化。通过单变量和多变量分析，探讨了随着时间的推移 Cr-eGFR 变化与达芦那韦/考比司他单药或达芦那韦/考比司他联合度鲁特韦和/或利匹韦林的使用之间的关系，同时调整了不同 HIV 患者特征、社会人口统计学特征、HIV 严重程度和除抗逆转录病毒药物以外的替诺福韦伴随药物的使用。
分析纳入了 725 名患者。在 48 周时，两种或更多种 IPTCrS（达芦那韦/考比司他联合利匹韦林和/或度鲁特韦）的联合使用与 Cr-eGFR 降低更大相关[调整后的中位数差异（±SD）-3.5±1.6（95%CI-6.6 至-0.3），P=0.047]，且下降幅度达到或超过 15 mL/min/1.73 m2 的情况更为常见[调整后的比值比（OR）3.233（95%CI 1.343-7.782），P=0.009]，与达芦那韦/考比司他单药治疗相比。在 12、24 和 48 周时，与达芦那韦/考比司他相比，使用两种或更多种 IPTCrS 的患者的 Cr-eGFR 变化显示出更显著的降低。（临床试验.gov：NCT03042390）。
达芦那韦/考比司他联合 IPTCrS 度鲁特韦、利匹韦林或两者联合使用可产生预期的 Cr-eGFR 下降的附加作用。
