Clinical Development and Medical Affairs, Boehringer Ingelheim (Canada) Ltd., Burlington, ON, Canada.
Drugs R D. 2011 Dec 1;11(4):295-302. doi: 10.2165/11596340-000000000-00000.
The POTENT trial compared the safety and efficacy of tipranavir/ritonavir (TPV/r) to darunavir/ritonavir (DRV/r), each with an optimized background regimen (OBR) in triple-class experienced HIV-1-infected patients with resistance to more than one protease inhibitor (PI).
METHODOLOGY/PRINCIPAL FINDINGS: POTENT was a prospective, open-label study of triple-class (PI, non-nucleoside reverse transcriptase inhibitors [NNRTI], nucleoside reverse transcriptase inhibitors [NRTI]), treatment-experienced, HIV-positive patients. Subjects were randomized to either TPV/r (500/200 mg twice daily) or DRV/r (600/100 mg twice daily) on a genotype-guided, investigator-selected OBR. CD4+ counts and HIV viral loads were assayed at key timepoints. The primary endpoint was time to virologic failure (viral load ≥500copies/mL). POTENT was prematurely terminated due to slow enrollment. Thirty-nine patients were treated with either TPV/r (n = 19) or DRV/r (n = 20); 82% were male, 77% White, with mean age of 43.6 years. Mean baseline HIV RNA was 3.9 log(10) copies/mL. Median prior antiretrovirals was 11, with no prior raltegravir or maraviroc exposure. Raltegravir was the most common novel class agent in the OBRs (n = 14 TPV/r; n = 12 DRV/r). In both groups, patients achieved mean viral load decreases ≥2 log(10) copies/mL by week 8, and by week 12 mean CD4+ counts rose by 40-50 cells/mm3. Total observation time was 32 weeks. Drug-related adverse events were reported in 21% (TPV/r) and 25% (DRV/r) of patients.
CONCLUSIONS/SIGNIFICANCE: TPV/r- and DRV/r-based regimens showed similar short-term safety and efficacy. These data support the use of next-generation PIs such as tipranavir or darunavir with novel class antiretroviral agents (integrase inhibitors, CCR5 antagonists, or fusion inhibitors).
POTENT 试验比较了替拉那韦/利托那韦（TPV/r）和达芦那韦/利托那韦（DRV/r）在对一种以上蛋白酶抑制剂（PI）耐药的经三种药物治疗的 HIV-1 感染患者中与优化背景方案（OBR）联合应用的安全性和疗效。
方法/主要发现：POTENT 是一项针对经三种药物（PI、非核苷类逆转录酶抑制剂[NNRTI]、核苷类逆转录酶抑制剂[NRTI]）、治疗经验丰富、HIV 阳性的患者的前瞻性、开放性研究。受试者根据基因型和研究者选择的 OBR 随机分配至 TPV/r（500/200mg 每日两次）或 DRV/r（600/100mg 每日两次）治疗。在关键时间点检测 CD4+细胞计数和 HIV 病毒载量。主要终点是病毒学失败时间（病毒载量≥500 拷贝/mL）。由于入组缓慢，POTENT 提前终止。39 例患者接受了 TPV/r（n=19）或 DRV/r（n=20）治疗；82%为男性，77%为白人，平均年龄为 43.6 岁。基线时平均 HIV RNA 为 3.9log10 拷贝/mL。中位既往抗逆转录病毒药物为 11 种，无既往拉替拉韦或马拉维若暴露。拉替拉韦是 OBR 中最常用的新型药物（TPV/r 组 n=14；DRV/r 组 n=12）。两组患者在第 8 周时均达到了平均病毒载量下降≥2log10 拷贝/mL，第 12 周时平均 CD4+细胞计数增加了 40-50 个/mm3。总观察时间为 32 周。报告了 21%（TPV/r）和 25%（DRV/r）的患者出现了药物相关不良事件。
结论/意义：TPV/r 和 DRV/r 方案显示出相似的短期安全性和疗效。这些数据支持使用替拉那韦或达芦那韦等下一代 PI 与新型抗逆转录病毒药物（整合酶抑制剂、CCR5 拮抗剂或融合抑制剂）联合应用。
