McDonald Cheryl K, Martorell Claudia, Ramgopal Moti, Laplante Francois, Fisher Martin, Post Frank A, Liu Yapei, Curley Joanne, Abram Michael E, Custodio Joseph, Graham Hiba, Rhee Martin S, Szwarcberg Javier
Tarrant County Infectious Disease, Fort Worth, Texas.
The Research Institute, Springfield, Massachusetts.
HIV Clin Trials. 2014 Nov-Dec;15(6):269-73. doi: 10.1310/hct1506-269.
Cobicistat (COBI) is a pharmacoenhancer that optimizes systemic exposures of protease inhibitors (PIs) such as atazanavir (ATV) and darunavir (DRV).
To evaluate the efficacy and safety of switching ritonavir (RTV) to COBI in patients with creatinine clearance (CrCl) 50 to 89 mL/min who are virologically suppressed on a stable regimen containing ritonavir (RTV)-boosted ATV or DRV. Other components of the regimen remained unchanged.
A phase 3, non-comparative, open-label clinical trial.
Seventy-three patients were enrolled. At week 48, 82% maintained virologic suppression. No emergent resistance developed. Serious adverse events (AEs) occurred in 7%, and study drug discontinuation due to AEs occurred in 10% (7 patients). There were 2 renal discontinuations and no cases of proximal renal tubulopathy. Small reductions in CrCl (median [IQR]) were observed as early as week 2, after which they were nonprogressive through week 48 (-3.8 [-9 to 0.8]). Changes in CrCl by baseline CrCl (< 70 vs ≥ 70) were -1.1 [-6.5 to 6.3] versus -6.6 [-12.4 to -0.7], respectively.
In HIV-1-infected patients with CrCl 50 to 89 mL/min switching from RTV to COBI, COBI-boosted PIs in combination with 2 nucleos(t)ide reverse transcriptase inhibitors were well-tolerated and effective in maintaining virologic suppression. The renal safety profile of COBI in this study was consistent with the long-term data in patients without renal impairment from the phase 3 studies of COBI-containing regimens.
考比司他（COBI）是一种药物增强剂，可优化阿扎那韦（ATV）和达芦那韦（DRV）等蛋白酶抑制剂（PIs）的全身暴露量。
评估在肌酐清除率（CrCl）为50至89 mL/分钟、接受含利托那韦（RTV）增强的ATV或DRV稳定方案且病毒学得到抑制的患者中，将利托那韦（RTV）换为考比司他（COBI）的疗效和安全性。方案的其他成分保持不变。
一项3期、非对照、开放标签的临床试验。
纳入73例患者。在第48周时，82%的患者维持病毒学抑制。未出现新的耐药情况。7%的患者发生严重不良事件（AE），10%（7例患者）因AE停用研究药物。有2例因肾脏问题停药，无近端肾小管病变病例。早在第2周就观察到CrCl有小幅下降（中位数[四分位间距]），此后直至第48周均无进展（-3.8[-9至0.8]）。根据基线CrCl（<70 vs≥70），CrCl的变化分别为-1.1[-6.5至6.3]和-6.6[-12.4至-0.7]。
在CrCl为50至89 mL/分钟、从RTV换为COBI的HIV-1感染患者中，COBI增强的PIs联合2种核苷（酸）逆转录酶抑制剂耐受性良好，且在维持病毒学抑制方面有效。本研究中考比司他的肾脏安全性与含考比司他方案的3期研究中无肾脏损害患者的长期数据一致。
