STUDIES IN SUBJECTS WITH LONG-TERM NONPROGRESSIVE HUMAN-IMMUNODEFICIENCY-VIRUS INFECTION
STUDIES IN SUBJECTS WITH LONG-TERM NONPROGRESSIVE HUMAN-IMMUNODEFICIENCY-VIRUS INFECTION
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DOI：
10.1056/nejm199501263320402
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发表时间：
1995-01-26
影响因子：
158.5
通讯作者：
FAUCI, AS
中科院分区：
文献类型：
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作者：
PANTALEO, G;MENZO, S;FAUCI, AS
背景。在感染1型人类免疫缺陷病毒（HIV - 1）的一小部分人群中，疾病没有进展，CD4 + T细胞计数多年保持稳定。对这些人的组织病理学、病毒学和免疫学特征的研究可能有助于深入了解导致HIV疾病的致病机制以及防止发展为显性疾病的保护机制。
方法与结果。我们研究了15名患有长期非进展性HIV感染的受试者和18名患有进展性HIV疾病的受试者。非进展性感染定义为有7年或更长时间的HIV感染记录，每立方毫米CD4 + T细胞超过600个，未接受抗逆转录病毒治疗，且无HIV相关疾病。非进展性感染受试者的淋巴结增生特征明显较少，且没有进展性疾病受试者淋巴结所具有的退化特征。非进展性感染受试者的血浆HIV - 1 RNA水平和外周血单核细胞中的病毒载量均显著低于进展性疾病受试者（分别为P = 0.003和P = 0.015）。无法从前者的血浆中分离出HIV，前者的中和抗体滴度也显著高于后者。然而，在非进展性感染受试者中存在病毒复制，并且始终能从淋巴结的单核细胞中培养出病毒。在淋巴结中，病毒“捕获”随生发中心的形成程度而变化，通过原位杂交发现表达病毒的细胞很少。在接受检测的所有7名非进展性感染受试者中均检测到HIV特异性细胞毒性活性。
结论。在尽管感染HIV但多年未患病的人群中，病毒载量较低，但病毒复制持续存在。淋巴结结构和免疫功能似乎保持完整。
Background. In a small percentage of persons infected with human immunodeficiency Virus type 1 (HIV-1), there is no progression of disease and CD4+ T-cell counts remain stable for many years. Studies of the histopathological, virologic, and immunologic characteristics of these persons may provide insight into the pathogenic mechanisms that lead to HIV disease and the protective mechanisms that prevent progression to overt disease.Methods and Results. We studied 15 subjects with long-term nonprogressive HIV infection and 18 subjects with progressive HIV disease. Nonprogressive infection was defined as seven or more years of documented HIV infection, with more than 600 CD4+ T cells per cubic millimeter, no antiretroviral therapy, and no HIV-related disease. Lymph nodes from the subjects with nonprogressive infection had significantly fewer of the hyperplastic features, and none of the involuted features, characteristic of nodes from subjects with progressive disease. Plasma levels of HIV-1 RNA and the viral burden in peripheral-blood mononuclear cells were both significantly lower in the subjects with nonprogressive infection than in those with progressive disease (P = 0.003 and P = 0.015, respectively). HIV could not be isolated from the plasma of the former, who also had significantly higher titers of neutralizing antibodies than the latter. There was viral replication, however, in the subjects with nonprogressive infection, and virus was consistently cultured from mononuclear cells from the lymph nodes. In the lymph nodes virus ''trapping'' varied with the degree of formation of germinal centers, and few cells expressing virus were found by in situ hybridization. HIV-specific cytotoxic activity was detected in ail seven subjects with nonprogressive infection who were tested.Conclusions. in persons who remain free of disease for many years despite HIV infection the Viral load is low, but viral replication persists. Lymph-node architecture and immune function appear to remain intact.