PILOT STUDY - A5173

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。设计：A5173是一项有限地点的单臂试点研究，旨在测量静息记忆中HIV-1感染患者静止记忆中HIV-1复制能力的清除情况，这些患者在接受逆转录酶和蛋白酶的融合抑制剂(恩福韦肽，以前的T-20)时，HIV-1 RNA水平受到抑制。持续时间：96周样本量：40名受试者人群：HIV-1感染者，血浆HIV-1RNA水平？1000拷贝/毫升，CD4细胞计数？100细胞/毫米~3，谁接受过？7天的任何其他抗逆转录病毒治疗。如果有证据表明最近的HIV-1血清转换，或者如果筛选的基因显示逆转录酶或蛋白酶存在初级耐药突变，受试者将不符合条件。方案：恩福韦90 mg，每日2次，替诺福韦300 mg，po，qd，恩曲他滨200 mg，po，qd，沙奎那韦硬质凝胶胶囊1000 mg，po，2次，利托那韦100 mg，2次。受试者和他们的医疗保健提供者可以为该方案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版本下进入试验的受试者可以继续服用拉米夫定，或者可以改用研究提供的恩曲他滨。所有受试者的潜伏细胞库将在24周时进行采样，除了那些永久停用恩福韦德或所有研究药物的受试者。在第24周血浆HIV-1RNA达到50拷贝/毫升的受试者将在第48、72和96周对他们的潜伏细胞库进行采样。24周时血浆HIV-1RNA未达到50拷贝/毫升的受试者将接受跟踪，但不会接受潜伏细胞库的额外评估。这些受试者可以继续接受研究药物，包括恩夫韦肽，并将进行安全监测，如方案中所述。他们将被允许在与研究小组协商后，由其提供者S酌情修改他们的方案。在第24周和整个研究期间血浆HIV-1RNA为50拷贝/毫升的受试者，或者单次测量为50拷贝/毫升但重新检测时为50拷贝/毫升的受试者，将是这项研究的主要焦点。24周后血浆HIV-1RNA确诊为50拷贝/毫升但未确认为200拷贝/毫升的受试者，将有权在其提供者-S酌情与研究团队协商后接受强化治疗，他们将继续获得用于潜伏病毒检测的样本。在24周后连续两次病毒载量-200拷贝/毫升的受试者将达到病毒学失败的方案定义，不再为潜在宿主分析提供样本。这些受试者可以继续接受研究药物，包括恩夫韦肽，并将进行安全监测，如方案中所述。他们将被允许在与研究小组协商后，由其提供者S酌情修改他们的方案。类内药物替代将被允许考虑毒性、耐受性和/或依从性困难。注：就本研究而言，核苷和核苷酸类似物将被视为同一类别。

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.