PILOT STUDY - A5173

试点研究 - A5173

• 批准号: 7381032
• 负责人: Jorge Santana
• 金额: $ 2.02万
• 依托单位: UNIVERSITY OF PUERTO RICO MED SCIENCES
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-07-01 至 2007-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7381032
• 关键词: PILOT; STUDY; A5173

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. DESIGN: A5173 is a limited-site, single-arm pilot study to measure the clearance of replication-competent HIV-1 in resting memory CD4+ cells in treatment-naive HIV-1-infected subjects who then have HIV-1 RNA levels suppressed while receiving a fusion inhibitor (enfuvirtide, formerly T-20) + inhibitors of reverse transcriptase and protease. DURATION: 96 weeks SAMPLE SIZE: 40 subjects POPULATION: HIV-1-infected individuals with plasma HIV-1 RNA levels ?1000 copies/mL and CD4+ cell counts ?100 cells/mm3, and who have had ?7 days of any other antiretroviral therapy. Subjects will be ineligible if there is evidence of recent HIV-1 seroconversion, or if the screening genotype shows the existence of a primary resistance mutation in reverse transcriptase or protease. REGIMEN: Enfuvirtide 90 mg sq BID + tenofovir 300 mg po QD + emtricitabine 200 mg po QD + saquinavir hard gel capsules 1000 mg po BID + ritonavir 100 mg po BID. Subjects and their health care providers may choose another protease inhibitor for the regimen; however, only saquinavir and ritonavir will be provided by the study. Subjects who entered under Version 1.0 may continue to take lamivudine or may switch to the study-provided emtricitabine. All subjects will have their latent cell reservoir sampled at week 24 except those who have permanently discontinued enfuvirtide or all study medications. Subjects who achieve a plasma HIV-1 RNA of 50 copies/mL at week 24 will have their latent cell reservoir sampled at weeks 48, 72, and 96. Subjects who do not achieve a plasma HIV-1 RNA of 50 copies/mL at week 24 will be followed but will not undergo additional evaluation of the latent cell reservoir. These subjects may continue to receive study medications, including enfuvirtide, and will have safety monitoring as outlined in the protocol. They will be allowed to modify their regimen at their provider?s discretion in consultation with the study team. Subjects who have a plasma HIV-1 RNA 50 copies/mL at week 24 and throughout the duration of the study, or who have single measurements ?50 copies/mL but who are 50 copies/mL when retested, will be the primary focus of this study. Subjects who have a confirmed plasma HIV-1 RNA ?50 copies/mL after week 24 that is not confirmed to be ?200 copies/mL will have the option of undergoing treatment intensification at their provider?s discretion in consultation with the study team, and they will continue to have samples obtained for latent reservoir assays. Subjects who have two consecutive viral loads ?200 copies/mL after week 24 will have met the protocol definition of virologic failure and will no longer contribute samples for the latent reservoir analysis. These subjects may continue to receive study medications, including enfuvirtide, and will have safety monitoring as outlined in the protocol. They will be allowed to modify their regimen at their provider?s discretion in consultation with the study team. Within-class drug substitutions will be allowed for toxicity, tolerability, and/or adherence difficulty. Note: For the purposes of this study, nucleoside and nucleotide analogues will be considered to be in the same class.

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。产品设计：A5173是一项有限中心、单臂初步研究，旨在测量未经治疗的HIV-1感染受试者静息记忆CD 4+细胞中有复制能力的HIV-1的清除率，这些受试者在接受融合抑制剂（恩夫韦肽，前身为T-20）+逆转录酶和蛋白酶抑制剂治疗时HIV-1 RNA水平受到抑制。 持续时间：96周样本量：40例受试者人群：HIV-1感染者血浆HIV-1 RNA水平？1000拷贝/mL和CD 4+细胞计数？100个细胞/mm 3，谁有过？7天的任何其他抗逆转录病毒治疗。如果有近期HIV-1血清转换的证据，或者如果筛选基因型显示逆转录酶或蛋白酶存在原发性耐药突变，则受试者不合格。 方案：恩夫韦肽90 mg sq BID +替诺福韦300 mg po QD +恩曲他滨200 mg po QD +沙奎那韦硬凝胶胶囊1000 mg po BID +利托那韦100 mg po BID。 受试者及其医疗保健提供者可选择另一种蛋白酶抑制剂用于治疗方案;但是，本研究仅提供沙奎那韦和利托那韦。根据第1.0版入组的受试者可继续服用拉米夫定或可转换为研究提供的恩曲他滨。 除永久停用恩夫韦肽或所有研究药物的受试者外，所有受试者将在第24周采集潜伏细胞库样本。 第24周时血浆HIV-1 RNA达到50拷贝/mL的受试者将在第48、72和96周时对其潜伏细胞库进行采样。 将对第24周时血浆HIV-1 RNA未达到50拷贝/mL的受试者进行随访，但不会对潜伏细胞库进行额外评价。这些受试者可以继续接受研究药物，包括恩夫韦肽，并将按照方案中的规定进行安全性监测。他们将被允许在他们的供应商修改他们的方案？与研究团队协商后，由研究团队自行决定。 第24周和整个研究期间血浆HIV-1 RNA 50拷贝/mL的受试者，或有单次测量结果的受试者？<50拷贝/mL但复检时<50拷贝/mL的受试者将是本研究的主要关注点。 确认有血浆HIV-1 RNA的受试者？第24周后<50拷贝/mL，但未确认为？200拷贝/mL将可以选择在其提供者处接受强化治疗？在与研究小组协商后，他们将继续获得用于潜在储层分析的样品。 受试者是否有连续两次病毒载量？第24周后200拷贝/mL将符合病毒学失败的方案定义，将不再为潜在储库分析提供样本。这些受试者可以继续接受研究药物，包括恩夫韦肽，并将按照方案中的规定进行安全性监测。他们将被允许在他们的供应商修改他们的方案？与研究团队协商后，由研究团队自行决定。 类内药物替代将允许毒性，耐受性和/或依从性困难。注：出于本研究的目的，核苷和核苷酸类似物将被视为同一类别。