ASSESSMENT OF ALVEOLAR MACROPHAGES AS A RESERVOIR FOR HIV

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 针对HIV-1感染的高效抗逆转录病毒疗法(HAART)显著提高了HIV感染儿童和成人的寿命和生活质量。然而，即使HAART阻止了病毒的复制，也有病毒藏身的地方，一旦停止药物治疗，病毒就会开始复制。此外，来自持续复制的抗药性病毒威胁到艾滋病毒治疗的寿命。尽管接受了抑制血液中病毒的治疗，但仍有相当一部分患者继续进行复制。此复制在正文中持续的位置是未知的。一种可能性是这种复制持续存在于称为巨噬细胞的特定肺细胞中。巨噬细胞对某些艾滋病毒药物的敏感性较低，因为这些细胞不会将药物转化为活性形式，或者细胞需要更高浓度的药物来阻止复制。此外，很难将足够的药物输送到肺巨噬细胞。为了确定肺巨噬细胞是否既是HIV-1感染的蓄水池又是持续复制的场所，我们每年通过诱导痰收集肺巨噬细胞，并在临床访问时收集额外的血液，以比较20名接受HAART的儿童血细胞中的病毒和肺细胞中的病毒。通过详细的基因分析，我们将能够确定肺细胞是否是艾滋病毒注射的储存库，以及肺巨噬细胞是否是持续复制的场所。如果肺巨噬细胞继续复制，而在血液中被抑制，那么未来的研究将被建议评估不同的抗HIV药物方案在肺巨噬细胞中的活性。

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. Highly active antiretroviral therapy (HAART) for HIV-1 infection has significantly improved the lifespan and quality of life of HIV-infected children and adults. However, even when replication of the virus is halted by HAART, there are reservoirs where the virus hides and will begin to replicate once drug-therapy is stopped. Additionally, drug-resistant virus from continued replication threatens the longevity of HIV therapy. A significant portion of patients continue to have replication despite therapy that keeps the virus suppressed in the blood. The location or locations in the body where this replication persists is unknown. One possibility is that the replication persists in the specific lung cells, called macrophages. Macrophages are less susceptible to some of the HIV-drugs because the cells do not convert the drug to the active form or the cells require a much higher concentration of the drug to stop replication. Additionally, it is difficult to get enough of the drug to the lung macrophages. In order to determine if lung macrophages are both a reservoir and a site of persistent replication of HIV-1 infection, we are collecting lung macrophages by induced sputum yearly and extra blood at clinical visits to compare the virus in the blood cells to the virus in the lung cells in 20 children on HAART. Through detailed genetic analyses, we will be able to determine if the lung cells are a reservoir of HIV-injection and if lung macrophages are a site of persistent replication. If replication continues in the lung macrophages when suppressed in the blood, then future studies will be proposed to evaluate the activity of different anti-HIV drug regimens in the lung macrophages.