ACTG A5175: ONCE-DAILY ARV THERAPY FOR HIV-1 IN RESOURCE-LIMITED SETTINGS

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 以前的大多数抗逆转录病毒疗法(ARV)试验都是在北美和欧洲的经济发达国家进行的。大多数艾滋病毒-1感染者生活在世界上资源有限的地区。现有数据表明，严格坚持治疗是ARV疗效的主要决定因素。由于可能影响依从性的因素(例如，药物毒性、共病和营养状况)在资源有限的国家可能有所不同，因此在这种情况下，抗逆转录病毒疗法的相对疗效也可能不同。增加依从性的一种方法是通过减少方案中的药片数量和每天的剂量来降低ARV方案的复杂性。预计简单的每日一次方案将增加依从性，从而提高ARV的疗效。每日一次方案的提供也将促进实施直接观察的抗逆转录病毒药物递送模型。因此，在资源有限的情况下，需要较少每日一次服药的三种抗逆转录病毒药物组合在治疗艾滋病毒-1感染方面具有潜在优势。 因此，这项研究假设，在资源有限的情况下，每天一次使用2个核苷类似物逆转录酶抑制剂(NRTI)+一个蛋白酶抑制剂(PI)或一个非NRTI(NNRTI)治疗并不比包含NNRTI的每日两次方案差。这项研究的终点是1)死亡，2)治疗12周后的疾病发展，或3)病毒学失败，定义为HIV RNA和GT；在治疗16周后连续两次测量为1000拷贝/毫升。 在步骤1(每个站点10名患者)中，美国和国际ACTG站点的大约1500名接受治疗的NA患者(包括曾接受过预防艾滋病毒母婴传播的短程ZDV和/或NVP的孕妇)将被随机分为3组：1)3TC/ZDV BID+EFV OD；2)FTC/ATV/DDI-EC；3)FTC/TDF/EFV OD。在步骤2中，有资格进行切换的患者--例如，病毒学失败、疾病进展、CD4计数最高下降50%--将根据现场调查员的判断，切换到步骤1中使用的三种或更多A5175研究药物和/或无法通过A5175获得的非研究药物的任何可行组合。注册将按原籍国家和艾滋病毒RNA(每毫升100,000份拷贝)分层。30%的患者进行意向治疗分析

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. Most previous trials of antiretroviral therapy (ARV) have been conducted in economically developed countries of North America and Europe. Most HIV-1-infected persons live in resource-limited areas of the world. Existing data suggest that strict adherence to treatment is a major determinant of ARV efficacy. Since factors that could affect adherence (e.g., drug toxicity, co-morbidities, and nutritional status) are likely to differ in resource-limited countries, the relative efficacy of ARV regimens in such settings may also differ. One approach to increase adherence is to decrease the complexity of ARV regimens by decreasing the number of pills in the regimen and the number of doses per day. It is expected that simple once-daily regimens will increase adherence and therefore ARV efficacy. The availability of once-daily regimens will also facilitate the implementation of directly observed models of ARV delivery. Thus, three-drug ARV combinations that require fewer pills dosed once-daily have potential advantages for the treatment of HIV-1 infection in resource-limited settings. This study, therefore, hypothesizes that once-daily treatment with 2 nucleoside analogue reverse transcriptase inhibitors (NRTIs) plus a protease inhibitor (PI) or plus a non-NRTI (NNRTI) is not inferior to a twice-daily regimen containing the NNRTI in a resource-limited setting. Endpoints of the study are 1) death, 2) disease progression after 12 weeks of therapy, or 3) virologic failure defined as an HIV RNA>1,000 copies/ml on 2 successive measurements after 16 weeks of treatment. In Step 1 (10 patients per site), about 1500 treatment-na¿ve patients (including previously pregnant women who have been treated with short-course ZDV and/or NVP for HIV prophylaxis of mother-to-child transmission) in the United States and at International ACTG sites will be randomized into 3 arms: 1) 3TC/ZDV BID + EFV OD; 2) FTC/ATV/DDI-EC OD; 3) FTC/TDF/EFV OD. In Step 2, patients who qualify for a switch - e.g., virologic failure, disease progression, decreased CD4 count <50% maximum - will be offered a switch to any viable combination of three or more of the A5175-provided study drugs used in Step 1 and/or non-study drugs not available through A5175, at the discretion of the site investigator. Enrollment will be stratified by country of origin and by HIV RNA (either > or < 100,000 copies per ml). Intent-to-treat analysis performed when 30% of