PILOT STUDY - A5173

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。设计：A5173是一项有限部位、单臂的试点研究，旨在测量在未接受治疗的HIV-1感染受试者的静息记忆CD4+细胞中复制能力HIV-1的清除率，这些受试者随后在接受融合抑制剂（恩福韦肽，以前的T-20） +逆转录酶和蛋白酶抑制剂的同时抑制HIV-1 RNA水平。持续时间：96周样本量：40名受试者人群：血浆HIV-1 RNA水平的HIV-1感染者？1000拷贝/mL和CD4+细胞计数？100个细胞/mm3，谁有过？任何其他抗逆转录病毒治疗的7天。如果有证据表明近期有HIV-1血清转化，或者筛选基因型显示存在逆转录酶或蛋白酶的原发性耐药突变，受试者将不合格。方案：恩福韦肽90mg sq BID +替诺福韦300mg po QD +恩曲他滨200mg po QD +沙奎那韦硬凝胶胶囊1000mg po BID +利托那韦100mg po BID。受试者和他们的医疗保健提供者可以选择另一种蛋白酶抑制剂；然而，该研究将只提供沙奎那韦和利托那韦。在1.0版本下进入的受试者可以继续服用拉米夫定，也可以改用研究提供的恩曲他滨。除永久停用恩孚韦肽或所有研究药物的受试者外，所有受试者将在第24周取样其潜伏细胞库。24周时血浆HIV-1 RNA达到50拷贝/mL的受试者将在48周、72周和96周时对其潜伏细胞库进行采样。在第24周，血浆HIV-1 RNA未达到50拷贝/mL的受试者将进行随访，但不进行潜在细胞库的额外评估。这些受试者可以继续接受包括恩福韦肽在内的研究药物，并按照方案进行安全监测。他们将被允许在他们的供应商那里修改他们的治疗方案？与研究小组协商后酌定。在第24周和整个研究期间血浆HIV-1 RNA为50拷贝/mL的受试者，还是只进行一次测量的受试者？50拷贝/mL，但重新测试时是50拷贝/mL，将是本研究的主要焦点。确认血浆HIV-1 RNA的受试者？第24周后的50份/毫升，不确定？200拷贝/mL的患者是否可以选择在其提供者处进行强化治疗？在与研究小组协商后，他们将继续获得用于潜在水库分析的样本。有连续两次病毒载量的受试者？24周后200拷贝/mL即符合病毒学失败的协议定义，不再为潜在库分析提供样本。这些受试者可以继续接受包括恩福韦肽在内的研究药物，并按照方案进行安全监测。他们将被允许在他们的供应商那里修改他们的治疗方案？与研究小组协商后酌定。对于毒性、耐受性和/或依从性困难，将允许类内药物替代。注：为了本研究的目的，核苷和核苷酸类似物将被认为属于同一类。

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.