PACTG 1015: INTERRUPTING HAART IN HIV+ CHILDREN W/ LOW VIRAL LOADS

PACTG 1015：在病毒载量低的 HIV 儿童中中断 HAART

• 批准号: 7378257
• 负责人: William Borkowsky
• 金额: $ 1万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-04-01 至 2007-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7378257
• 关键词: PACTG; 1015; INTERRUPTING; HAART; HIV+

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. The purposes of this multicenter are to determine if brief intervals of highly active antiretroviral therapy (HAART) suspension result in increased HIV-specific CD8 and/or CD4 activity; to determine whether the increase in such activity will result in prolonged suppression of viremia with subsequent suspension of HAART; to determine whether the stimulation of HIV-specific immunity reduces HIV proviral load; and to determine whether cycles of HAART drug holidays of increasing duration result in the emergence of drug-resistant virus or if drug-sensitive virus persists. The rationale is that some HIV-infected patients taking HAART have been able to achieve prolonged suppression of HIV plasma viremia for extended periods of time. However, attempts to discontinue HAART have consistently resulted in the return of HIV in the plasma, suggesting that cell-associated HIV may be a factor. The elimination of cell-associated HIV is dependent on a number of immune-mediated mechanisms, including CD8 cells. Although CD8 cells are frequently detected in individuals with incomplete HIV suppression, it has been noted that both CD8 and CD4 cells are markedly reduced in individuals with prolonged HIV suppression. It is hypothesized that a brief and low-level increase in HIV viremia, resulting from suspension of HAART, might boost HIV-specific CD8 and CD4 T-cells. After the subsequent suppression of viremia with the reintroduction of HAART, the expanded CD8 population might be able to better control viral replication or to eliminate some of the cell-associated HIV. This could result in a more prolonged period of aviremia with a subsequent suspension of HAART.

该子项目是利用 NIH/NCRR 资助的中心拨款提供的资源的众多研究子项目之一。子项目和研究者 (PI) 可能已从另一个 NIH 来源获得主要资金，因此可以在其他 CRISP 条目中得到体现。列出的机构是中心的机构，不一定是研究者的机构。该多中心的目的是确定短暂间隔的高效抗逆转录病毒治疗 (HAART) 暂停是否会导致 HIV 特异性 CD8 和/或 CD4 活性增加；确定这种活性的增加是否会导致病毒血症的长期抑制并随后暂停HAART；确定 HIV 特异性免疫的刺激是否会降低 HIV 前病毒载量；并确定延长持续时间的HAART药物假期周期是否会导致耐药病毒的出现，或者药物敏感病毒是否持续存在。 其基本原理是，一些接受HAART的HIV感染患者能够在较长时间内实现对HIV血浆病毒血症的长期抑制。然而，停止HAART的尝试始终导致血浆中HIV重新出现，这表明细胞相关的HIV可能是一个因素。细胞相关 HIV 的消除依赖于许多免疫介导的机制，包括 CD8 细胞。尽管在 HIV 抑制不完全的个体中经常检测到 CD8 细胞，但人们注意到，在长期 HIV 抑制的个体中 CD8 和 CD4 细胞均显着减少。据推测，HAART 暂停导致 HIV 病毒血症短暂且低水平增加，可能会增强 HIV 特异性 CD8 和 CD4 T 细胞。随后重新引入HAART抑制病毒血症后，扩大的CD8群体可能能够更好地控制病毒复制或消除一些与细胞相关的HIV。这可能会导致更长时间的无病毒血症，并随后暂停 HAART。