INTERMITTENT WITHDRAWAL OF ANTIRETROVIRAL THERAPY-IMMUNIZATION WITH ALVAC-HIV

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。这是一项随机的I/II阶段试点研究，旨在评估间歇停用有效的抗逆转录病毒治疗作为免疫策略、ALVAC-HIV免疫以及这两种策略联合使用的安全性、抗病毒效果和免疫学效果。将有100名感染艾滋病毒的受试者入学。受试者目前正在接受他们的第一次有效的抗逆转录病毒治疗(有效的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，在进入研究之前持续6个月以上，CD4+T细胞计数为400个细胞/mm^3。HIV-1RNA水平在进入研究前6个月以上为400拷贝/毫升，在需要进行研究筛查时为50拷贝/毫升。研究的期限约为两年。受试者将被随机分配到四组中的一组(每组25人)：A组：安慰剂免疫(ALVAC安慰剂)+有效的ART，为期92周，一个12-20周的停药期。B组：安慰剂免疫(ALVAC安慰剂)+有效ART，疗程84周，包括4-6周停药期、4周停药期和12-20周停药期。C组：疫苗免疫(ALVAC VCP1452)+有效ART，疗程92周，停药12-20周。D组：疫苗免疫(ALVAC VCP1452)+有效ART治疗84周，1个4-6周停药期，1个4周停药期，1个12-20周停药期。本研究将作为一项多步骤研究进行管理。对于B组和D组的受试者，在接受ALVAC免疫的同时进行有效的ART治疗的时间段之后，将交替停止和恢复治疗。在头44周的研究中，A组和C组的受试者将继续进行有效的ART，并进行三组疫苗接种。在44-46周的研究之后，所有受试者都将根据病毒应答和CD4+计数在一段时间内停止治疗。A5068有3个身体隔室亚组研究，将量化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.