ACTG A5095: 3 PROTEASE INHIBITOR-SPARING REGIMENS FOR INITIAL TREATMENT OF HIV

ACTG A5095：HIV 初始治疗的 3 种保留蛋白酶抑制剂的方案

• 批准号: 7378252
• 负责人: JUDITH Ann ABERG
• 金额: $ 1万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-04-01 至 2007-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7378252
• 关键词: ACTG; A5095; PROTEASE; INHIBITOR; SPARING

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This is a randomized, double-blind comparison of three protease inhibitor (PI)-sparing regimens for the initial treatment of HIV infection with the goal being to suppress and maintain HIV-1 levels <200 copies/ml. The safety and tolerability of the 3 initial PI-sparing regimens will also be determined. The rationale for conducting this study is that current treatment guidelines recommend combination regimens of 2 nucleoside analogues with either a PI or a nonnucleoside reverse transcriptase inhibitor (NNRTI) as the preferred therapy for the initial treatment of HIV infection. However, the efficacy of current regimens is limited by their complexity, pharmacokinetic characteristics, short- and long-term side effects, and drug-resistance profiles at the time of virologic failure. Consequently, the identification of new initial regimens that are simpler, better tolerated, preserve treatment options in the event of virologic failure, and improve on antiretroviral potency is needed. In addition, recent concern over the long-term toxicities of PIs and the extensive cross-resistance among the available PIs have led to the testing of "PI-sparing" regimens. The methodology consists of the following: Step 1: Patients are randomly selected to receive 1 of 3 blinded treatment regimens: abacavir (ABC)/lamivudine (3TC)/zidovudine (ZDV)/efavirenz (EFV), ABC/3TC/ZDV, or 3TC/ZDV/EFV. Patients with confirmed virologic failure on Step 1 and confirmed plasma HIV RNA levels of 10,000 copies/ml or greater must register to Step 2. Patients with confirmed virologic failure on Step 1 and plasma HIV RNA < 10,000 copies/ml may remain on Step 1 or register to Step 2. Step 2: Step 2 is open label. Regimens include 2 nucleoside reverse transcriptase inhibitors (NRTIs) in combination with either EFV or BMS-232632. Based on genotypic resistance results, the NRTI combination may be a fixed-dose combination of 3TC/ZDV or 2 of the following: ZDV, didanosine (ddI), 3TC, stavudine (d4T), and ABC; however, the ZDV/d4T combination is not permitted. Clinical assessments and laboratory evaluations are done at entry, at Weeks 2, 4, 6, 8, 12, 16, 20, 24, and then every 8 weeks thereafter for the duration of the study. Evaluations are also required when a protocol-allowed drug substitution is made. In addition, 2 substudies are being conducted: a neurology substudy for efavirenz and a pharmacology substudy for BMS-232632.

该子项目是利用 NIH/NCRR 资助的中心拨款提供的资源的众多研究子项目之一。子项目和研究者 (PI) 可能已从另一个 NIH 来源获得主要资金，因此可以在其他 CRISP 条目中得到体现。列出的机构是中心的机构，不一定是研究者的机构。这是对 HIV 感染初始治疗的三种蛋白酶抑制剂 (PI) 保留方案进行的随机、双盲比较，目的是抑制和维持 HIV-1 水平<200 拷贝/ml。还将确定 3 种初始 PI 保留方案的安全性和耐受性。进行这项研究的理由是，当前的治疗指南建议将 2 种核苷类似物与 PI 或非核苷逆转录酶抑制剂 (NNRTI) 的组合方案作为 HIV 感染初始治疗的首选疗法。然而，当前治疗方案的功效受到其复杂性、药代动力学特征、短期和长期副作用以及病毒学失败时的耐药情况的限制。因此，需要确定更简单、耐受性更好、在病毒学失败时保留治疗选择并提高抗逆转录病毒效力的新初始治疗方案。此外，最近对 PI 的长期毒性和现有 PI 之间广泛的交叉耐药性的担忧导致了“PI 保留”方案的测试。该方法包括以下内容： 第 1 步：随机选择患者接受 3 种盲法治疗方案中的一种：阿巴卡韦 (ABC)/拉米夫定 (3TC)/齐多夫定 (ZDV)/依非韦伦 (EFV)、ABC/3TC/ZDV 或 3TC/ZDV/EFV。在步骤 1 中确认病毒学失败且血浆 HIV RNA 水平达到 10,000 拷贝/ml 或更高的患者必须注册至步骤 2。在步骤 1 中确认病毒学失败且血浆 HIV RNA < 10,000 拷贝/ml 的患者可以继续在步骤 1 中进行或注册至步骤 2。 步骤 2：步骤 2 是开放标签。治疗方案包括 2 种核苷逆转录酶抑制剂 (NRTI) 与 EFV 或 BMS-232632 的组合。根据基因型耐药结果，NRTI组合可以是3TC/ZDV或以下2种的固定剂量组合：ZDV、去羟肌苷(ddI)、3TC、司他夫定(d4T)和ABC；然而，ZDV/d4T 组合是不允许的。临床评估和实验室评估在入组时、第 2、4、6、8、12、16、20、24 周进行，然后在研究期间每 8 周进行一次。当进行方案允许的药物替代时也需要进行评估。此外，还有两项子研究正在进行中：依非韦伦的神经学子研究和 BMS-232632 的药理学子研究。