Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA.
J Infect Dis. 2012 Jun;205(11):1730-8. doi: 10.1093/infdis/jis260. Epub 2012 Mar 23.
Individuals infected with human immunodeficiency virus (HIV) have higher risk than HIV-negative individuals for diseases associated with aging. T-cell senescence, characterized by expansion of cells lacking the costimulatory molecule CD28, has been hypothesized to mediate these risks.
We measured the percentage of CD28(-)CD4(+) and CD8(+) T cells from HIV-infected treatment-naive adults from 5 Adult Clinical Trials Group (ACTG) antiretroviral therapy (ART) studies and the ALLRT (ACTG Longitudinal Linked Randomized Trials) cohort, and from 48 HIV-negative adults. Pretreatment and 96-week posttreatment %CD28(-) cells were assessed using linear regression for associations with age, sex, race/ethnicity, CD4 count, HIV RNA, ART regimen, and hepatitis C virus (HCV) infection.
In total, 1291 chronically HIV-infected adults were studied. Pretreatment, lower CD4 count was associated with higher %CD28(-)CD4(+) and %CD28(-)CD8(+) cells. For CD8(+) cells, younger age and HCV infection were associated with a lower %CD28(-). ART reduced %CD28(-) levels at week 96 among virally suppressed individuals. Older age was strongly predictive of higher %CD28(-)CD8(+). Compared to HIV-uninfected individuals, HIV-infected individuals maintained significantly higher %CD28(-).
Effective ART reduced the proportion of CD28(-) T cells. However, levels remained abnormally high and closer to levels in older HIV-uninfected individuals. This finding may inform future research of increased rates of age-associated disease in HIV-infected adults.
感染人类免疫缺陷病毒 (HIV) 的个体比 HIV 阴性个体更容易患与衰老相关的疾病。细胞缺乏共刺激分子 CD28 的扩增被认为介导了这些风险，这种现象被称为 T 细胞衰老。
我们从 5 项成人临床试验组 (ACTG) 抗逆转录病毒治疗 (ART) 研究和 ALLRT（ACTG 纵向链接随机试验）队列中，以及从 48 名 HIV 阴性成年人中，测量了未经治疗的 HIV 感染成年患者中 CD28(-)CD4(+) 和 CD8(+)T 细胞的百分比。使用线性回归评估治疗前和 96 周后 %CD28(-)细胞与年龄、性别、种族/民族、CD4 计数、HIV RNA、ART 方案和丙型肝炎病毒 (HCV) 感染的关系。
共研究了 1291 例慢性 HIV 感染的成年人。治疗前，较低的 CD4 计数与更高的 %CD28(-)CD4(+) 和 %CD28(-)CD8(+)细胞相关。对于 CD8(+)细胞，年龄较小和 HCV 感染与较低的 %CD28(-)相关。在病毒抑制的个体中，ART 在第 96 周降低了 %CD28(-)水平。年龄较大与较高的 %CD28(-)CD8(+)密切相关。与 HIV 未感染者相比，HIV 感染者保持着明显更高的 %CD28(-)。
有效的 ART 降低了 CD28(-)T 细胞的比例。然而，水平仍然异常高，更接近 HIV 未感染者中老年人的水平。这一发现可能为未来研究 HIV 感染者中与年龄相关疾病的高发率提供信息。
