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的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 以前的大多数抗逆转录病毒疗法试验是在北美和欧洲经济发达国家进行的。 大多数HIV-1感染者生活在世界上资源有限的地区。 现有数据表明，严格坚持治疗是抗逆转录病毒药物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、合并症和营养状况）在资源有限的国家可能不同，因此抗逆转录病毒疗法在这些环境中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抗逆转录病毒治疗方案中的药丸数量和每天的剂量数量来降低抗逆转录病毒治疗方案的复杂性。 预计简单的每日一次方案将增加依从性，从而提高ARV疗效。 提供每日一次的治疗方案也将有助于实施直接观察的抗逆转录病毒药物输送模式。 因此，三种药物的抗逆转录病毒药物组合，需要更少的药丸剂量每天一次，有潜在的优势，用于治疗艾滋病毒-1感染的资源有限的设置。 因此，本研究假设，在资源有限的情况下，2种核苷类似物逆转录酶抑制剂（NRTI）加蛋白酶抑制剂（PI）或加非NRTI（NNRTI）每日一次治疗不劣于含NNRTI的每日两次方案。 研究的终点是1）死亡，2）治疗12周后疾病进展，或3）病毒学失败，定义为治疗16周后连续2次测量HIV RNA> 1，000拷贝/ml。 在第1步（每个研究中心10例患者）中，美国和国际ACTG研究中心约1500例初治患者（包括既往接受过短程ZDV和/或NVP预防母婴传播HIV治疗的妊娠女性）将随机分为3组：1）3 TC/ZDV BID + EFV OD; 2）FTC/ATV/DDI-EC OD; 3）FTC/TDF/EFV OD。 在步骤2中，有资格转换的患者-例如，病毒学失败、疾病进展、CD 4计数降低<50%最大值-将根据研究中心研究者的判断，转换为步骤1中使用的三种或更多种A5175提供的研究药物和/或A5175无法获得的非研究药物的任何可行组合。 将按来源国和HIV RNA（>或<100，000拷贝/ml）对入组进行分层。 当30%的

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