García F, Niebla G, Romeu J, Vidal C, Plana M, Ortega M, Ruiz L, Gallart T, Clotet B, Miró J M, Pumarola T, Gatell J M
Infectious Diseases Unit, Institut d'Investigacions Biomèdiques, August Pi I Sunyer Hospital Clínic, Faculty of Medicine, University of Barcelona, Spain.
AIDS. 1999 Aug 20;13(12):1491-6. doi: 10.1097/00002030-199908200-00008.
To assess HIV-1 RNA levels in cerebrospinal fluid (CSF) and their potential correlation with plasma viral load and central nervous system (CNS) HIV-1 infection markers in stable asymptomatic patients with a CD4 T cell count >500x10(6) cells/l.
Consecutive patients screened for two trials were eligible for lumbar puncture assessment. At day 0, simultaneous samples of CSF and plasma were obtained and levels of total proteins, albumin, IgG, antibodies against HIV-1 p24 antigen, HIV-1 RNA (using the polymerase chain technique) and white cells were measured.
The integrity of the blood-brain barrier was preserved (albumin index > or =7) in 59 out of 70 patients (84%). Intrathecal production of antibodies against HIV-1 p24 antigen was demonstrated in 55 out of 70 individuals (78%). Viral load in CSF was significantly lower than plasma values (3.13+/-0.95 versus 4.53+/-0.53, P = 0.0001). HIV-1 RNA was not detected in CSF in only three of the 70 patients (4%). Overall, there was a significant correlation between plasma and CSF HIV-1 RNA levels (r = 0.43, P = 0.0001); however, in 29 patients (41%) there were significant differences (>1.5 log10 copies/ml) between the viral loads in plasma and CSF. In the multivariate analysis, a high level of protein and white cells in CSF, but not the HIV-1 RNA plasma level, were factors independently associated with a higher level of HIV-1 RNA in CSF (P = 0.0001).
HIV-1 RNA can be detected almost always in CSF of asymptomatic patients in early stages of HIV-1 infection including those with a preserved integrity of the blood-brain barrier. The important discrepancies between plasma and CSF viral load, and the independent association between CSF abnormalities and CSF viral load, support the hypothesis of local production of HIV-1.
评估CD4 T细胞计数>500×10⁶细胞/升的稳定无症状患者脑脊液(CSF)中的HIV-1 RNA水平及其与血浆病毒载量和中枢神经系统(CNS)HIV-1感染标志物的潜在相关性。
连续入选两项试验的患者有资格接受腰椎穿刺评估。在第0天,同时采集CSF和血浆样本,测量总蛋白、白蛋白、IgG、抗HIV-1 p24抗原抗体、HIV-1 RNA(采用聚合酶链技术)和白细胞水平。
70例患者中有59例(84%)血脑屏障完整(白蛋白指数≥7)。70例个体中有55例(78%)显示有鞘内抗HIV-1 p24抗原抗体产生。CSF中的病毒载量显著低于血浆值(3.13±0.95对4.53±0.53,P = 0.0001)。70例患者中仅3例(4%)CSF中未检测到HIV-1 RNA。总体而言,血浆和CSF中HIV-1 RNA水平之间存在显著相关性(r = 0.43,P = 0.0001);然而,29例患者(41%)血浆和CSF中的病毒载量存在显著差异(>1.5 log₁₀拷贝/毫升)。在多变量分析中,CSF中高水平的蛋白和白细胞,但不是HIV-1 RNA血浆水平,是与CSF中较高水平的HIV-1 RNA独立相关的因素(P = 0.0001)。
在HIV-1感染早期的无症状患者的CSF中几乎总能检测到HIV-1 RNA,包括那些血脑屏障完整的患者。血浆和CSF病毒载量之间的重要差异,以及CSF异常与CSF病毒载量之间的独立关联,支持了HIV-1局部产生的假说。