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

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。这项多中心研究的目的是确定短暂暂停高活性抗逆转录病毒治疗（HAART）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，随后暂停HAART治疗；确定刺激HIV特异性免疫是否能降低HIV前病毒载量；并确定持续时间增加的HAART药物休假周期是否会导致耐药病毒的出现，或药物敏感病毒是否会持续存在。其基本原理是，一些接受HAART治疗的艾滋病毒感染者能够在较长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治疗的尝试一直导致血浆中HIV的复发，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。虽然CD8细胞经常在HIV不完全抑制的个体中检测到，但已经注意到CD8和CD4细胞在HIV长期抑制的个体中都显着减少。据推测，暂停HAART治疗导致HIV病毒血症的短暂低水平增加可能会增加HIV特异性CD8和CD4 t细胞。在随后重新引入HAART抑制病毒血症后，扩增的CD8群体可能能够更好地控制病毒复制或消除一些细胞相关的HIV。这可能导致更长的病毒血症期，随后暂停HAART治疗。

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.