Metabolic Effects of Darunavir/Ritonavir Versus Atazanavir/Ritonavir in Treatment-Naive, HIV Type 1-Infected Subjects over 48 Weeks
Metabolic Effects of Darunavir/Ritonavir Versus Atazanavir/Ritonavir in Treatment-Naive, HIV Type 1-Infected Subjects over 48 Weeks
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DOI：
10.1089/aid.2011.0327
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发表时间：
2012-10-01
影响因子：
1.5
通讯作者：
De La Rosa, Guy
中科院分区：
文献类型：
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作者：
Aberg, Judith A.;Tebas, Pablo;De La Rosa, Guy
我们评估了每天一次（qd）达芦那韦/利托那韦（DRV/r）与每日一次阿扎那韦/利托那韦（ATV/r）联合固定剂量替诺福韦/恩曲他滨的代谢变化。这是一项 4 期、多中心、开放标签、随机探索性研究。初治的 HIV-1 感染成人接受 DRV/r 800/100 mg 每日一次或 ATV/r 300/100 mg 每日一次，均联合恩曲他滨/替诺福韦 200/300 mg 每日一次。主要终点：甘油三酯水平从基线到第12周的变化。次要终点：第12周和第48周脂质参数的变化、胰岛素敏感性、炎症/凝血/细菌易位生物标志物、病毒载量、CD4(+)细胞计数以及第48周脂肪组织分布的变化和受试者对身体变化的感知。在 DRV/r 组中，分别有 32/34 和 29/34 的受试者完成了第 12 周和第 48 周；在 ATV/r 组中，分别有 30/31 和 25/31 的受试者完成了第 12 周和第 48 周。从基线到第 12 周和第 48 周，两组的血脂参数均观察到微小变化。第 12 周时，各组之间的总胆固醇（DRV/r，20.3 mg/dl；ATV/r，4.6 mg/dl）和载脂蛋白 A1（DRV/r，10.7 mg/dl；ATV/r，0.7 mg/dl）平均变化存在差异。在第 48 周，各组之间的任何血脂参数、空腹血糖或胰岛素敏感性变化均未发现临床相关差异。 48 周内，双臂的生物标志物普遍下降，功效参数有所改善。各组之间脂肪组织的变化很小并且具有可比性。两个研究组的受试者对身体变化的感知普遍有所改善。在 HIV-1 感染受试者中进行的首次试点比较表明，在 48 周的治疗过程中，DRV/r 的代谢特征与 ATV/r 相似。有必要进行进一步的随机研究。
We assessed metabolic changes for darunavir/ritonavir (DRV/r) once daily (qd) versus atazanavir/ritonavir (ATV/r) qd with fixed-dose tenofovir/emtricitabine. This was a phase 4, multicenter, open-label, randomized exploratory study. Treatment-naive, HIV-1-infected adults received DRV/r 800/100 mg qd or ATV/r 300/100 mg qd, both with emtricitabine/tenofovir 200/300 mg qd. Primary end point: change in triglyceride levels from baseline to week 12. Secondary end points: week 12 and week 48 changes in lipid parameters, insulin sensitivity, inflammatory/coagulation/bacterial translocation biomarkers, viral load, CD4(+) cell count, and week 48 changes in adipose tissue distribution and subjects' perceptions of body changes. In the DRV/r arm, 32/34 and 29/34 subjects completed weeks 12 and 48, respectively; in the ATV/r arm, 30/31 and 25/31 subjects completed weeks 12 and 48, respectively. Small changes in lipid parameters from baseline to weeks 12 and 48 were observed in both arms. Differences were noted between arms in mean changes in total cholesterol (DRV/r, 20.3 mg/dl; ATV/r, 4.6 mg/dl) and apolipoprotein A1 (DRV/r, 10.7 mg/dl; ATV/r, 0.7 mg/dl) at week 12. At week 48, no clinically relevant differences between arms were noted for changes in any lipid parameter, fasting glucose, or insulin sensitivity. Biomarkers generally decreased and efficacy parameters improved in both arms over 48 weeks. Changes in adipose tissue were small and comparable between arms. Subjects' perceptions of body changes generally improved in both study arms. This first pilot comparison in HIV-1-infected subjects suggests that DRV/r has a metabolic profile similar to ATV/r over 48 weeks of treatment. Further randomized studies are warranted.