INTERMITTENT WITHDRAWAL OF ANTIRETROVIRAL THERAPY-IMMUNIZATION WITH ALVAC-HIV

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来源获得了主要资金，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。这是一项随机I/II期初步研究，旨在评价间歇性停用强效抗逆转录病毒治疗作为免疫策略、ALVAC-HIV免疫以及两种策略联合使用的安全性、抗病毒作用和免疫学作用。将入组100例HIV感染受试者。受试者目前正在接受首次强效抗逆转录病毒治疗（强效ART），定义为三种或三种以上药物联合抗逆转录病毒治疗方案，在进入研究前持续6个月以上CD 4 + T细胞计数> 400个细胞/mm^3。HIV-1 RNA水平< 400拷贝/mL超过6个月研究入组前和< 50拷贝/mL在研究筛选要求。研究持续时间约为2年。受试者将以相同数量（每组25例）随机分配至四组之一：A组：安慰剂免疫（ALVAC安慰剂）+强效ART，持续92周，有一个12-20周的停药期。 B组：安慰剂免疫（ALVAC安慰剂）+强效ART，持续84周，包括一个4-6周停药期、一个4周停药期和一个12-20周停药期。C组：疫苗免疫（ALVAC vCP 1452）+强效ART，持续92周，有一个12-20周的停药期。D组：疫苗免疫（ALVAC vCP 1452）+强效ART，持续84周，包括1个4-6周停药期、1个4周停药期和1个12-20周停药期。本研究将作为多步骤研究进行管理。对于B组和D组的受试者，在接受ALVAC免疫接种的同时接受强效ART治疗的阶段之后，将交替进行停药和恢复治疗的阶段。A组和C组中的受试者将在研究的前44周内保持有效的ART，其中三组疫苗施用。在研究44-46周后，所有组中的受试者将根据病毒应答和CD 4+计数停止治疗一段时间。A5068有3个体室子研究，将定量潜伏感染细胞群的大小。

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. This is a randomized phase I/II pilot study intended to evaluate the safety, antiviral effects and immunological effects of intermittent withdrawal of potent antiretroviral therapy as an immunization strategy, ALVAC-HIV immunization, and the two strategies combined. One hundred HIV-infected subjects will be enrolled. Subjects currently receiving their first potent antiretroviral treatment (potent ART), defined as three-or-more-drug combination antiretroviral therapy regimen, with persistent CD4+ T-cell counts > 400 cells/mm^3 for more than 6 months before study entry. HIV-1 RNA levels < 400 copies/mL for more than 6 months before study entry and < 50 copies/mL at study screening required. The duration of the study will be approximately 2 years. Subjects will be randomized in equal numbers (25 per arm) to one of four arms: Arm A: Placebo immunization (ALVAC placebo) + potent ART for 92 weeks with one 12-20 week therapy withdrawal period. Arm B: Placebo immunization (ALVAC placebo) + potent ART for 84 weeks with one 4-6 week therapy withdrawal period, one 4-week therapy withdrawl period, and one 12-20 week withdrawal period. Arm C: Vaccine immunization (ALVAC vCP1452) + potent ART for 92 weeks with one 12-20 week therapy withdrawal period. Arm D: Vaccine immunization (ALVAC vCP1452) + potent ART for 84 weeks with one 4-6 week therapy withdrawal period, one 4-week therapy withdrawal period, and one 12-20 week therapy withdrawal period. This study will be managed as a multiple-step study. For subjects in Arms B and D, periods on potent ART therapy while receiving ALVAC immunizations will be followed by alternating periods of therapy withdrawal and resumption. Subjects in Arms A and C will remain on potent ART with three sets of vaccine administrations for the first 44 weeks on study. Following 44-46 weeks on study, subjects in all arms will then have therapy withdrawn for a period depending on viral response and CD4+ counts. There are 3 body compartment substudies of A5068 which will quantitate the size of the latently infected cell population.