Sevigny J J, Albert S M, McDermott M P, McArthur J C, Sacktor N, Conant K, Schifitto G, Selnes O A, Stern Y, McClernon D R, Palumbo D, Kieburtz K, Riggs G, Cohen B, Epstein L G, Marder K
Columbia University and The Taub Institute, New York, NY 10032, USA.
Neurology. 2004 Dec 14;63(11):2084-90. doi: 10.1212/01.wnl.0000145763.68284.15.
To evaluate whether baseline levels of plasma and CSF HIV RNA, tumor necrosis factor alpha (TNFalpha), monocyte chemoattractant protein-1 (MCP-1), matrix metalloproteinase-2 (MMP-2), or macrophage colony stimulating factor (M-CSF) are predictors of incident HIV-associated dementia (HIVD) in a cohort with advanced HIV infection.
A total of 203 nondemented subjects with CD4 lymphocyte counts less than 200/muL, or <300/microL but with cognitive impairment, underwent semiannual neurologic, cognitive, functional, and laboratory assessments. HIVD and minor cognitive motor disorder (MCMD) were defined using American Academy of Neurology criteria. The cumulative incidence of HIVD was estimated using Kaplan-Meier curves. Cox proportional hazards regression models were used to examine the associations between biologic variables and time to HIVD, adjusting for age, sex, years of education, duration of HIV infection, type of antiretroviral use, premorbid IQ score, and presence of MCMD.
After a median follow-up time of 20.7 months, 74 (36%) subjects reached the HIVD endpoint. The dementia was mild in 70% of cases. The cumulative incidence of HIVD was 20% at 1 year and 33% at 2 years. Highly active antiretroviral therapy (HAART) was used by 73% of subjects at baseline. A plasma HIV RNA level was undetectable in 23% of subjects and a CSF HIV RNA level was undetectable in 48% of subjects. In adjusted analyses, neither plasma nor CSF HIV RNA levels (log10) were associated with time to HIVD; log10 levels of plasma TNFalpha (HR 3.07, p = 0.03) and CSF MCP-1 (HR = 3.36, p = 0.06) tended to be associated with time to HIVD.
The lack of association between baseline plasma and CSF HIV RNA levels and incident dementia suggests highly active antiretroviral therapy may be affecting CNS viral dynamics, leading to lower HIV RNA levels, and therefore weakening the utility of baseline HIV RNA levels as predictors of HIV-associated dementia.
评估血浆和脑脊液中人类免疫缺陷病毒RNA（HIV RNA）、肿瘤坏死因子α（TNFα）、单核细胞趋化蛋白-1（MCP-1）、基质金属蛋白酶-2（MMP-2）或巨噬细胞集落刺激因子（M-CSF）的基线水平是否为晚期HIV感染队列中发生HIV相关痴呆（HIVD）的预测指标。
共有203名CD4淋巴细胞计数低于200/μL或低于300/μL但有认知障碍的非痴呆受试者，每半年接受一次神经学、认知、功能和实验室评估。HIVD和轻度认知运动障碍（MCMD）根据美国神经病学学会标准进行定义。使用Kaplan-Meier曲线估计HIVD的累积发病率。采用Cox比例风险回归模型来检验生物学变量与发生HIVD时间之间的关联，并对年龄、性别、受教育年限、HIV感染持续时间、抗逆转录病毒药物使用类型、病前智商得分和MCMD的存在情况进行校正。
在中位随访时间20.7个月后，74名（36%）受试者达到HIVD终点。70%的病例痴呆为轻度。HIVD的累积发病率在1年时为20%，2年时为33%。73%的受试者在基线时使用了高效抗逆转录病毒治疗（HAART）。23%的受试者血浆HIV RNA水平检测不到，48%的受试者脑脊液HIV RNA水平检测不到。在校正分析中，血浆和脑脊液HIV RNA水平（log10）均与发生HIVD的时间无关；血浆TNFα的log10水平（风险比3.07，p = 0.03）和脑脊液MCP-1的log10水平（风险比 = 3.36，p = 0.06）倾向于与发生HIVD的时间相关。
基线血浆和脑脊液HIV RNA水平与新发痴呆之间缺乏关联表明，高效抗逆转录病毒治疗可能正在影响中枢神经系统的病毒动态，导致HIV RNA水平降低，因此削弱了基线HIV RNA水平作为HIV相关痴呆预测指标的效用。
