Early immune activation predicts central nervous system disease in HIV-infected infants: implications for early treatment.
Early immune activation predicts central nervous system disease in HIV-infected infants: implications for early treatment.
复制标题
早期免疫激活可预测艾滋病毒感染婴儿的中枢神经系统疾病：对早期治疗的影响。
DOI：
10.1086/595886
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发表时间：
2009
期刊：
影响因子：
--
通讯作者：
Kovacs,Andrea
中科院分区：
文献类型：
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作者：
Kovacs,Andrea
One of the most serious consequences of HIV infection in both adults and children is the development of CNS disorders that range from mild cognitive abnormalities to frank encephalopathy and HIV-associated dementia [1]. In the case of an infant or child, however, the ultimate outcome can be devastating, because brain growth and neurodevelopment are also dramatically affected. Domestic and international studies suggest that, without antiretroviral therapy, 50%–90% of HIV-infected infants and children have some form of CNS disease [1–5]. This may include delays in language expression and cognitive function, developmental delays, motor deficits, or behavioral problems. Of HIV-infected infants, 12%–23% develop frank encephalopathy, typically in the first year of life, and this may occur precipitously [3–5]. Given that, worldwide, there are 2.5 million infants and children infected with HIV and 420,000 new infections each year among infants and children, the consequences of HIV-associated CNS disease are potentially disastrous. For this reason, it is essential to better understand the pathogenesis of CNS disease so that better treatments can be designed. Since early in the AIDS epidemic, there has been much research attempting to understand the pathogenesis of HIV-associated CNS disease. Although the exact timing of infection of the brain is unknown, it is believed that HIV seeds the CNS during primary viremia, when HIV-infected monocytes or T cells traverse the bloodbrain barrier [6, 7]. HIV infection acquired either in utero, intrapartum, or postpartum via breast milk occurs when the immune system is immature, when the brain is growing and developing, and when the infant is experiencing other bacterial and viral infections for the first time. For this reason, an infant or child has more-rapid disease progression and earlier manifestations of CNS disease than does an adult infected with HIV [1]. Given the catastrophic potential complications related to CNS disease in infants and children, the study by Mekmullica et al.[8] in this issue of Clinical Infectious Diseases has implications not only for early identification and treatment of infants at risk for CNS disease but also for our understanding of the basic pathogenesis of early encephalopathy. In the study, the authors evaluated neurobehavioral data, using the Bayley scales of infant development, performed from birth through age 30 months among 98 infants who also had CD8 activation data from the first 2 months of life obtained as part of the Women and Infants Transmission Study in 1989–1994. The outcome was the time to development of a mental development index (MDI) and psychomotor developmental index (PDI) 11 SD below the mean. The level of CD8+ T cell activation, measured using the markers CD38 and HLA-DR, in the first 2 months of life was then assessed using 2-color flow cytometry and was correlated with development of HIV-associated CNS disease. The definitions for early low activation versus early high activation were defined and tested elsewhere: 5% versus 15% CD8+HLADR+ T cells and 25% versus 125% CD8+CD38+ T cells [9]. Adjustments were made in the multivariate models for typical confounding maternal and infant factors, such as the timing of infection (ie, in utero vs. intrapartum). The most significant finding of the study by Mekmullica et al.[8] was the strong association between performance
