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

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。该多中心研究的目的是确定短期暂停高效抗逆转录病毒治疗（HAART）是否会导致HIV特异性CD 8和/或CD 4活性增加;确定这种活性的增加是否会导致随后暂停HAART的病毒血症长期抑制;确定刺激HIV特异性免疫是否会降低HIV前病毒载量;并确定持续时间不断增加的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治疗的HIV感染患者能够在较长时间内实现HIV血浆病毒血症的长期抑制。然而，试图停止HAART一直导致艾滋病毒在血浆中的返回，这表明细胞相关的艾滋病毒可能是一个因素。细胞相关HIV的消除依赖于许多免疫介导的机制，包括CD 8细胞。虽然在HIV抑制不完全的个体中经常检测到CD 8细胞，但已经注意到，在HIV抑制延长的个体中，CD 8和CD 4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加HIV特异性CD 8和CD 4 T细胞。在随后通过再次引入HAART抑制病毒血症后，扩增的CD 8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。这可能导致更长时间的病毒血症，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.