Carotenuto P, Looij D, Keldermans L, de Wolf F, Goudsmit J
Department of Human Retrovirology, Academic Medical Centre, University of Amsterdam, The Netherlands.
AIDS. 1998 Sep 10;12(13):1591-600. doi: 10.1097/00002030-199813000-00005.
To assess the dynamics of neutralizing antibodies (NAb) in long-term AIDS-free HIV-1-infected subjects and establish correlations with known markers of disease progression.
Cross-sectional study using sera collected from long-term non-progressors (LTNP) 8 years after seroconversion or study entry. Longitudinal study using sera collected from LTNP at 0, 0.5, 1, 2, 4, 6, 8 and 10 years after seroconversion and, as controls, from rapid progressors.
Individuals with documented AIDS-free HIV-1 infection for at least 8 years were evaluated for NAb against five heterologous HIV-1 primary isolates. In the cross-sectional study, serum viral RNA levels, CD4+ T-cell numbers and T-cell function were determined on samples collected during the eighth year of follow-up. For the longitudinal study, NAb were assessed in sequential sera taken from LTNP and rapid progressors.
Serum neutralization titres found in individual sera differed from one HIV-1 isolate to another, were detected in 49-76% of LTNP, without correlation with the coreceptor usage of the isolate, and were positively associated with CD4+ T-lymphocyte counts (P = 0.0041) and T-cell function (P = 0.04). No correlation was found between NAb and the level of viral RNA in serum or the rate of CD4+ T-cell decline. Longitudinal analysis of sera from LTNP and rapid progressors showed that although several subjects in both groups had neutralizing activity at seroconversion, it thereafter became lower or no longer detectable. NAb were again found 1-4 years later and stably persisted in LTNP, but remained undetectable or at low levels in rapid progressors.
NAb were preferentially found in subjects with relatively preserved T-cell function and CD4+ T-cell numbers. In these individuals, neutralizing activity against heterologous isolates increased with time. These data suggest that the capacity to produce broadly NAb is a function of the integrity of the immune system.
评估长期无艾滋病的HIV-1感染者体内中和抗体（NAb）的动态变化，并建立其与已知疾病进展标志物的相关性。
横断面研究，使用血清转化或研究入组8年后从长期非进展者（LTNP）收集的血清。纵向研究，使用血清转化后0、0.5、1、2、4、6、8和10年从LTNP收集的血清，并以快速进展者作为对照。
对记录在案的至少8年无艾滋病的HIV-1感染者进行评估，检测其针对五种异源HIV-1原始毒株的中和抗体。在横断面研究中，测定随访第8年采集样本的血清病毒RNA水平、CD4+ T细胞数量和T细胞功能。对于纵向研究，在从LTNP和快速进展者采集的连续血清中评估中和抗体。
个体血清中发现的血清中和滴度因HIV-1毒株而异，在49%-76%的LTNP中检测到，与毒株的共受体使用情况无关，且与CD4+ T淋巴细胞计数呈正相关（P = 0.0041）和T细胞功能呈正相关（P = 0.04）。未发现中和抗体与血清中病毒RNA水平或CD4+ T细胞下降速率之间存在相关性。对LTNP和快速进展者血清的纵向分析表明，尽管两组中的一些受试者在血清转化时具有中和活性，但此后其活性降低或不再可检测到。1-4年后再次发现中和抗体，且在LTNP中稳定持续存在，但在快速进展者中仍不可检测或处于低水平。
中和抗体在T细胞功能和CD4+ T细胞数量相对保留的受试者中更常见。在这些个体中，针对异源毒株的中和活性随时间增加。这些数据表明产生广泛中和抗体的能力是免疫系统完整性的一种功能。
