Cohen O J, Pantaleo G, Lam G K, Fauci A S
Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-1876, USA.
Springer Semin Immunopathol. 1997;18(3):305-22. doi: 10.1007/BF00813500.
Lymphoid tissue is a major reservoir of human immunodeficiency virus (HIV) infection in vivo. In addition, the lymphoid microenvironment provides a replicative advantage to the virus in that it provides a milieu of activated target cells that allows for efficient virus spread. The process of mobilization and activation of immune competent cells directed against the virus paradoxically contributes to the propagation of virus replication. Disruption of the lymphoid microenvironment during the progression of HIV disease is a poorly understood process, which may be of considerable importance pathogenically. Studies of lymph node biopsy samples taken 8 weeks apart from individuals who did not undergo any change in their therapeutic regimen (i.e., patients who either remained untreated or remained on their ongoing nucleoside analogue reverse transcriptase inhibitor monotherapy regimen) revealed little change in histopathology or viral load over the 8-week period. These results with successive lymph node biopsy samples taken from different sites indicate that an isolated lymph node biopsy accurately reflects the pathologic process associated with HIV infection and that this process diffusely involves the lymphoid system. Treatment with reverse transcriptase inhibitor monotherapy of patients in relatively early stage HIV disease had no detectable impact on the viral load in lymphoid tissue, suggesting the need to investigate more potent antiretroviral regimens during this stage of disease. Among patients with moderately advanced HIV disease, switching to combination therapy from a monotherapy regimen resulted in decreased viral replication in lymph nodes; this effect was associated with decreases in plasma viremia. Despite the fact that measures of viral replication decreased significantly, the net frequency of HIV-infected cells in peripheral blood and lymph nodes remained unchanged. Potent antiretroviral drug combinations may be capable of profound and long-term downregulation of plasma viremia. It will be essential to monitor the status of viral trapping, viral burden, and viral replication within lymphoid tissue during treatment with such drugs to determine accurately their true potential for impact on these key features of HIV pathogenesis.
淋巴组织是体内人类免疫缺陷病毒（HIV）感染的主要储存库。此外，淋巴微环境为病毒提供了复制优势，因为它提供了一个活化靶细胞的环境，有利于病毒的有效传播。针对病毒的免疫活性细胞的动员和激活过程，却反常地促进了病毒复制的传播。在HIV疾病进展过程中，淋巴微环境的破坏是一个了解甚少的过程，这在致病机制上可能相当重要。对未改变治疗方案（即要么未接受治疗，要么继续接受核苷类似物逆转录酶抑制剂单一疗法）的个体每隔8周采集的淋巴结活检样本进行研究发现，在这8周期间，组织病理学或病毒载量几乎没有变化。从不同部位采集的连续淋巴结活检样本的这些结果表明，单次淋巴结活检能准确反映与HIV感染相关的病理过程，且这一过程广泛累及淋巴系统。对处于相对早期HIV疾病的患者进行逆转录酶抑制剂单一疗法治疗，对淋巴组织中的病毒载量没有可检测到的影响，这表明在疾病的这一阶段需要研究更有效的抗逆转录病毒方案。在中度进展期HIV疾病患者中，从单一疗法改为联合疗法可导致淋巴结中病毒复制减少；这种效果与血浆病毒血症的降低有关。尽管病毒复制指标显著下降，但外周血和淋巴结中HIV感染细胞的净频率仍保持不变。强效抗逆转录病毒药物组合可能能够对血浆病毒血症进行深度和长期的下调。在用此类药物治疗期间，监测淋巴组织内病毒捕获、病毒负荷和病毒复制的状态，对于准确确定它们对HIV发病机制这些关键特征的真正影响潜力至关重要。
