Disease Progression in HIV-1-Infected Viremic Controllers.
Disease Progression in HIV-1-Infected Viremic Controllers.
复制标题
DOI：
10.1097/qai.0b013e318269c414
复制
发表时间：
2012-12-01
期刊：
影响因子：
--
通讯作者：
McKnight A
中科院分区：
文献类型：
--
作者：
Groves KC;Bibby DF;Clark DA;Isaksen A;Deayton JR;Anderson J;Orkin C;Stagg AJ;McKnight A
HIV-1感染中CD 4 + T细胞下降的机制尚不清楚，但与血浆病毒RNA载量的相关性表明涉及病毒复制。事实上，具有低病毒RNA载量的病毒血症控制者患者通常维持高的CD 4 + T细胞计数。在86个病毒血症控制者的本地队列中，我们确定了一个亚组（18个“不和谐控制者”），其CD 4 + T细胞计数低，存在临床不确定性。在血浆（RNA）病毒载量较低或检测不到时，导致CD 4 + T细胞下降的潜在机制仍未得到解决。本研究的目的是通过测量细胞HIV-1 DNA载量、T细胞群和T细胞活化标志物来研究不和谐控制者的病毒和宿主免疫系统动态。我们比较了不和谐控制者（病毒RNA载量<2000拷贝/mL，<450 CD 4 + T细胞/mm 3）与典型控制者（病毒RNA载量<2000拷贝/mL，>450 CD 4 + T细胞/mm 3）和进展者（病毒RNA载量> 10，000拷贝/mL，<450 CD 4 + T细胞/mm 3）。我们定量了CD 4 +/CD 8+幼稚/中枢记忆/效应记忆亚群（CD 45 RA/RO ± CD 62 L）、活化水平（CD 38 +HLA-DR+）和HIV-1 DNA载量。与典型控制者相比，不和谐控制者类似于表现出高病毒DNA载量、幼稚CD 4 + T细胞耗竭和所有CD 4 + T细胞亚群中较高活化的进展者。他们与典型的控制者相似，与进展者相比，CD 8 + T细胞活化较低。我们的数据与CD 4 + T细胞活化和疾病进展之间的关系一致。HIV-1 DNA载量可能比病毒RNA载量更能反映病毒复制和疾病进展。较低水平的CD 8 + T细胞活化与低病毒RNA载量相关，但与疾病进展或病毒DNA载量无关。
The mechanism of CD4+ T-cell decline in HIV-1 infection is unclear, but the association with plasma viral RNA load suggests viral replication is involved. Indeed, viremic controller patients with low viral RNA loads typically maintain high CD4+ T-cell counts. Within a local cohort of 86 viremic controllers, we identify a subgroup (18 “discord controllers”) with low CD4+ T-cell counts that present clinical uncertainty. The underlying mechanism accounting for CD4+ T-cell decline in the face of low or undetectable plasma (RNA) viral load remains unresolved. The objective of this study was to investigate the viral and host immune system dynamics in discord controllers by measuring cellular HIV-1 DNA load, T-cell populations, and T-cell activation markers. We compared discord controllers (viral RNA load <2000 copies/mL, <450 CD4+ T-cells/mm3) with typical controllers (viral RNA load <2000 copies/mL, >450 CD4+ T-cells/mm3) and progressors (viral RNA load >10,000 copies/mL, <450 CD4+ T-cells/mm3). We quantified CD4+/CD8+ naive/central memory/effector memory subsets (CD45RA/RO ± CD62L), activation levels (CD38+HLA-DR+), and HIV-1 DNA load. Discord controllers resembled progressors showing high viral DNA load, depletion of naive CD4+ T-cells, and higher activation in all CD4+ T-cell subsets, compared with typical controllers. They were similar to typical controllers with lower CD8+ T-cell activation compared with progressors. Our data are consistent with a relationship between CD4+ T-cell activation and disease progression. HIV-1 DNA load may be a better marker of viral replication and disease progression than viral RNA load. Lower level CD8+ T-cell activation correlates with low viral RNA load but not with disease progression or viral DNA load.