Valcour V G, Shiramizu B T, Sithinamsuwan P, Nidhinandana S, Ratto-Kim S, Ananworanich J, Siangphoe U, Kim J H, de Souza M, Degruttola V, Paul R H, Shikuma C M
Hawaii AIDS Clinical Research Program, John A. Burns School of Medicine, University of Hawaii, Honolulu, HI 96816, USA.
Neurology. 2009 Mar 17;72(11):992-8. doi: 10.1212/01.wnl.0000344404.12759.83.
The extent to which highly active antiretroviral therapy (HAART) era cognitive disorders are due to active processes, incomplete clearance of reservoirs, or comorbidities is controversial. This study aimed to determine if immunologic and virologic factors influence cognition after first-time HAART in Thai individuals with HIV-associated dementia (HAD) and Thai individuals without HAD (non-HAD).
Variables were captured longitudinally to determine factors predictive of degree of cognitive recovery after first-time HAART. Neuropsychological data were compared to those of 230 HIV-negative Thai controls.
HIV RNA and CD4 lymphocyte counts were not predictive of HAD cross-sectionally or degree of cognitive improvement longitudinally. In contrast, baseline and longitudinal HIV DNA isolated from monocytes correlated to cognitive performance irrespective of plasma HIV RNA and CD4 lymphocyte counts pre-HAART (p < 0.001) and at 48 weeks post HAART (p < 0.001). Levels exceeding 3.5 log(10) copies HIV DNA/10(6) monocyte at baseline distinguished all HAD and non-HAD cases (p < 0.001). At 48 weeks, monocyte HIV DNA was below the level of detection of our assay (10 copies/10(6) cells) in 15/15 non-HAD compared to only 4/12 HAD cases, despite undetectable plasma HIV RNA in 26/27 cases. Baseline monocyte HIV DNA predicted 48-week cognitive performance on a composite score, independently of concurrent monocyte HIV DNA and CD4 count (p < 0.001).
Monocyte HIV DNA level correlates to cognitive performance before highly active antiretroviral therapy (HAART) and 48 weeks after HAART in this cohort and baseline monocyte HIV DNA may predict 48-week cognitive performance. These findings raise the possibility that short-term incomplete cognitive recovery with HAART may represent an active process related to this peripheral reservoir.
在高效抗逆转录病毒治疗（HAART）时代，认知障碍在多大程度上是由活跃过程、病毒储存库清除不完全或合并症引起的，这一点存在争议。本研究旨在确定免疫和病毒学因素是否会影响首次接受HAART治疗的泰国HIV相关痴呆（HAD）患者和非HAD泰国患者的认知情况。
纵向记录变量，以确定首次接受HAART治疗后认知恢复程度的预测因素。将神经心理学数据与230名HIV阴性泰国对照者的数据进行比较。
HIV RNA和CD4淋巴细胞计数在横断面分析中不能预测HAD，在纵向分析中也不能预测认知改善程度。相比之下，无论HAART治疗前的血浆HIV RNA和CD4淋巴细胞计数如何，从单核细胞中分离出的基线和纵向HIV DNA均与认知表现相关（治疗前p<0.001，HAART治疗后48周p<0.001）。基线时HIV DNA水平超过3.5 log(10)拷贝/10(6)单核细胞可区分所有HAD和非HAD病例（p<0.001）。在48周时，15/15名非HAD患者的单核细胞HIV DNA低于我们检测方法的检测水平（10拷贝/10(6)细胞），而12名HAD患者中只有4名如此，尽管27例中有26例血浆HIV RNA检测不到。基线单核细胞HIV DNA可独立于同时期的单核细胞HIV DNA和CD4计数，预测48周时综合评分的认知表现（p<0.001）。
在该队列中，单核细胞HIV DNA水平与高效抗逆转录病毒治疗（HAART）前及HAART治疗后48周的认知表现相关，且基线单核细胞HIV DNA可能预测48周时的认知表现。这些发现增加了一种可能性，即HAART治疗后短期内认知恢复不完全可能代表与这种外周病毒储存库相关的活跃过程。
