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

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。这个多中心的目的是确定短暂的高效抗逆转录病毒疗法(HAART)暂停是否会导致艾滋病毒特异性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；确定刺激艾滋病毒特异性免疫是否会降低艾滋病毒前病毒载量；以及确定持续时间越来越长的HAART药物假期周期是否会导致耐药病毒的出现或药物敏感病毒的持续存在。其基本原理是，一些服用HAART的艾滋病毒感染患者能够在很长一段时间内实现对艾滋病毒血浆病毒血症的长期抑制。然而，停止HAART的尝试一直导致血浆中艾滋病毒的回归，这表明细胞相关艾滋病毒可能是一个因素。消除与细胞相关的艾滋病毒依赖于许多免疫介导的机制，包括CD8细胞。虽然在HIV抑制不完全的个体中经常检测到CD8细胞，但人们已经注意到，在长期抑制HIV的个体中，CD8和CD4细胞都显著减少。据推测，暂停HAART导致的HIV病毒血症的短暂和低水平增加，可能会增强HIV特异性CD8和CD4T细胞。在随后通过重新引入HAART来抑制病毒血症之后，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艾滋病毒。这可能会导致更长的禽血症时期，并随后暂停HAART。

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.