Overton Edgar Turner, Tebas Pablo, Coate Bruce, Ryan Robert, Perniciaro Amy, Dayaram Yaswant K, De La Rosa Guy, Baugh Bryan P
a Department of Medicine , University of Alabama School of Medicine , Birmingham , AL , USA.
b Department of Medicine , University of Pennsylvania , Philadelphia , PA , USA.
HIV Clin Trials. 2016 Mar;17(2):72-7. doi: 10.1080/15284336.2016.1141468.
The phase 4, METABOLIK trial demonstrated that changes in metabolic parameters with darunavir with low-dose ritonavir (DRV/r) were comparable to those observed with atazanavir with low-dose ritonavir (ATV/r). A comprehensive assessment of the effects of these agents on insulin sensitivity will provide additional, relevant clinical information.
In this substudy of METABOLIK, HIV-1-infected, antiretroviral agent-naïve male subjects aged ≥18 years with a viral load of >1,000 copies/mL were randomized to receive DRV/r 800/100 mg once daily (qd) or ATV/r 300/100 mg qd, both with a fixed dose of tenofovir disoproxil fumarate/emtricitabine 300/200 mg qd. The effects of DRV/r versus ATV/r on insulin sensitivity over 48 weeks were compared using the euglycemic hyperinsulinemic clamp, the preferred method to assess insulin sensitivity; primary end point was the effect on insulin sensitivity during the first 12 weeks.
Twenty-seven subjects completed the study. In the DRV/r arm (n=14), median glucose disposal from baseline through weeks 12 and 48 was 9.3, 11.4, and 9.9 mg/kgmin, respectively; in the ATV/r arm (n=13), these values were 8.9, 8.6, and 9.1 mg/kgmin, respectively. Median insulin sensitivity in the DRV/r arm at baseline, week 12, and week 48 was 24.0, 25.0, and 21.5 mg/kgmin per μIU/mL×100, respectively; these values in the ATV/r arm were 20.7, 22.0, and 22.0 mg/kgmin per μIU/mL×100, respectively. Most subjects had ≥1 adverse event, including three serious adverse events (n=2 [DRV/r], n=1 [ATV/r]).
DRV/r and ATV/r displayed similar modest effects on insulin sensitivity using a euglycemic hyperinsulinemic clamp.
4期METABOLIK试验表明，达芦那韦联合低剂量利托那韦（DRV/r）引起的代谢参数变化与阿扎那韦联合低剂量利托那韦（ATV/r）所观察到的变化相当。全面评估这些药物对胰岛素敏感性的影响将提供更多相关的临床信息。
在METABOLIK的这项子研究中，年龄≥18岁、病毒载量>1000拷贝/mL且未接受过抗逆转录病毒治疗的HIV-1感染男性受试者被随机分为两组，分别接受每日一次800/100mg的DRV/r或每日一次300/100mg的ATV/r，二者均联合固定剂量的富马酸替诺福韦二吡呋酯/恩曲他滨，每日300/200mg。采用正常血糖高胰岛素钳夹技术（评估胰岛素敏感性的首选方法）比较DRV/r与ATV/r在48周内对胰岛素敏感性的影响；主要终点是前12周对胰岛素敏感性的影响。
27名受试者完成了研究。在DRV/r组（n = 14）中，从基线到第12周和第48周的中位葡萄糖处置率分别为9.3、11.4和9.9mg/kg·min；在ATV/r组（n = 13）中，这些值分别为8.9、8.6和9.1mg/kg·min。DRV/r组在基线、第12周和第48周的中位胰岛素敏感性分别为每μIU/mL×100 24.0、25.0和21.5mg/kg·min；ATV/r组的这些值分别为每μIU/mL×100 20.7、22.0和22.0mg/kg·min。大多数受试者发生≥1次不良事件，包括3次严重不良事件（n = 2 [DRV/r]，n = 1 [ATV/r]）。
使用正常血糖高胰岛素钳夹技术时，DRV/r和ATV/r对胰岛素敏感性的影响相似且程度适中。
