Erlandson Kristine M, Allshouse Amanda A, Rapaport Eric, Palmer Brent E, Wilson Cara C, Weinberg Adriana, MaWhinney Samantha, Campbell Thomas B
1 Department of Medicine, University of Colorado , Aurora, Colorado.
2 Colorado School of Public Health , Aurora, Colorado.
AIDS Res Hum Retroviruses. 2015 Sep;31(9):905-12. doi: 10.1089/AID.2015.0085. Epub 2015 Jul 8.
Cytomegalovirus (CMV) is associated with poor outcomes, including physical function impairment, in older HIV-uninfected adults. Whether CMV is associated with physical functional impairment in HIV-infected adults is unknown. The primary objective of this study was to determine the relationship between CMV-specific humoral and cell-mediated immune responses with functional impairment in well-controlled HIV infection. In a case-control study, low-function cases were matched by age, gender, and time from HIV diagnosis to high-function controls. Quantitative CMV IgG and %CMV-specific CD8(+) and CD4(+) T cells (interferon-γ expression following CMV pp65 stimulation) were used to estimate physical function. Among 30 low-function cases and 48 high-function matched controls, CMV IgG ranged from <10 to 8,830 EU/ml, including four controls with results <10 EU/ml. Each log10 increase in CMV IgG was associated with 5-fold greater odds of low function (p=0.01); these findings were robust to adjustment for concomitant CD4(+) count, tobacco use, and age; to exclusion of subjects with CMV IgG <10 EU/ml; and to adjustment for hepatitis C viremia. %CMV-specific CD4(+) or CD8(+) T cells were not associated with low function. In bivariable models, the relationship between CMV IgG and physical function was attenuated and was no longer significant when including IL-6, CD4/CD8 ratio, or the Veterans Aging Cohort Study Index score. High levels of CMV-specific IgG were associated with impaired physical function. Attenuation of the strength of this association in bivariable models suggests an indirect relationship mediated by systemic inflammation and immune suppression.
巨细胞病毒（CMV）与未感染HIV的老年成年人的不良预后相关，包括身体功能受损。CMV是否与感染HIV的成年人的身体功能受损相关尚不清楚。本研究的主要目的是确定在HIV感染得到良好控制的情况下，CMV特异性体液免疫和细胞介导免疫反应与功能受损之间的关系。在一项病例对照研究中，低功能病例根据年龄、性别以及从HIV诊断到高功能对照的时间进行匹配。使用定量CMV IgG以及%CMV特异性CD8(+)和CD4(+) T细胞（CMV pp65刺激后的干扰素-γ表达）来评估身体功能。在30例低功能病例和48例高功能匹配对照中，CMV IgG范围为<10至8830 EU/ml，包括4例结果<10 EU/ml的对照。CMV IgG每增加1个对数10，低功能的几率就高5倍（p = 0.01）；这些发现对于伴随的CD4(+)计数、吸烟情况和年龄的调整具有稳健性；对于排除CMV IgG<10 EU/ml的受试者具有稳健性；对于丙型肝炎病毒血症的调整也具有稳健性。%CMV特异性CD4(+)或CD8(+) T细胞与低功能无关。在双变量模型中，当纳入白细胞介素-6、CD4/CD8比值或退伍军人老龄化队列研究指数评分时，CMV IgG与身体功能之间的关系减弱且不再显著。高水平的CMV特异性IgG与身体功能受损相关。在双变量模型中这种关联强度的减弱表明存在由全身炎症和免疫抑制介导的间接关系。
