Kalokhe Ameeta S, Ibegbu Chris C, Kaur Surinder P, Amara Rama R, Kelley Mary E, Del Rio Carlos, Stephenson Rob
Emory School of Medicine, Division of Infectious Diseases, Atlanta, GA; Emory Rollins School of Public Health, Department of Global Health, Atlanta, GA.
Yerkes National Primate Research Center, Emory University, Atlanta, GA; Emory Vaccine Center, Department of Microbiology and Immunology, Atlanta, GA.
Pathog Immun. 2016 Spring;1(1):193-213. doi: 10.20411/pai.v1i1.120.
Biological pathways mediating the link between intimate partner violence (IPV) and increased HIV risk remain unexplored. We hypothesized that IPV-induced stress negatively affects HIV systemic immune defenses and aimed to evaluate whether IPV was associated with immune profiles linked to HIV susceptibility: CD4 activation and diminished regulatory T-cell (Treg) frequency.
Seventy-five HIV-negative high-risk women were surveyed regarding their IPV experience. They provided blood, urine, and (if present) genital ulcer samples for cortisol, immune assays, and STI testing. Using flow cytometry, we assessed activated CD4 T-cell (%HLA-DR/CD38) and Treg (%CD4CD25FoxP3) frequencies and phenotyping. Nonparametric tests evaluated the association between IPV and immune outcomes. Multivariate regression explored confounding and moderation of the IPV-CD4 activation pathway.
Lifetime IPV was associated with increased CD4 activation (r = 0.331, = 0.004), a shift in CD4 phenotype from naïve to effector memory (r = 0.343, = 0.003), and a decrease in naive (%HLA-DR/CD45RA) Treg frequency (r = -0.337, = 0.003). Experiencing IPV over the past year had similar trends. After controlling for sexual IPV, lifetime physical and psychological abuse remained significantly associated with CD4 activation ( = 0.004 and = 0.033, respectively). After controlling for race (the only covariate linked to activation), the lifetime IPV-CD4 activation association remained significant ( = 0.012). Alcohol use and depression were identified as potential pathway moderators.
Our data is the first to suggest an immune link between IPV and HIV, and may help explain differences at the individual level in HIV susceptibility and response to biological HIV prevention strategies. The association of psychological and physical abuse with CD4 activation independent of sexual abuse further supports the existence of a stress-induced immune pathway.
介导亲密伴侣暴力（IPV）与HIV感染风险增加之间联系的生物学途径仍未得到探索。我们假设IPV诱发的应激会对HIV全身免疫防御产生负面影响，并旨在评估IPV是否与与HIV易感性相关的免疫特征有关：CD4激活和调节性T细胞（Treg）频率降低。
对75名HIV阴性的高危女性进行了关于她们IPV经历的调查。她们提供了血液、尿液以及（如有）生殖器溃疡样本用于皮质醇检测、免疫分析和性传播感染检测。我们使用流式细胞术评估活化的CD4 T细胞（%HLA-DR/CD38）和Treg（%CD4CD25FoxP3）频率及表型。非参数检验评估IPV与免疫结果之间的关联。多变量回归探讨了IPV-CD4激活途径的混杂因素和调节因素。
终生IPV与CD4激活增加相关（r = 0.331，P = 0.004），CD4表型从初始型向效应记忆型转变（r = 0.343，P = 0.003），以及初始（%HLA-DR/CD45RA）Treg频率降低（r = -0.337，P = 0.003）。在过去一年中经历IPV也有类似趋势。在控制了性方面的IPV后，终生身体和心理虐待仍与CD4激活显著相关（分别为P = 0.004和P = 0.033）。在控制了种族（与激活相关的唯一协变量）后，终生IPV与CD4激活之间的关联仍然显著（P = 0.012）。饮酒和抑郁被确定为潜在的途径调节因素。
我们的数据首次表明IPV与HIV之间存在免疫联系，并可能有助于解释个体在HIV易感性以及对生物HIV预防策略反应方面的差异。心理和身体虐待与CD4激活的关联独立于性虐待，这进一步支持了应激诱导免疫途径的存在。
