Elucidating Biopsychosocial Mediators of HIV Progression

描述(由申请人提供)：艾滋病毒进展过程中显著的个体差异表明心理神经免疫(PNI)机制被牵连。研究人员先前和初步的研究已经证明，适应不良的C型应对方式(情感上缺乏表达，不认识自己的需求或感受)与艾滋病毒进展之间存在纵向关系；C型应对方式与HIV特异性β趋化因子的产生减少之间存在横向关系，后者是CCR5 HIV辅受体的配体，与强大的艾滋病毒抑制活性有关。这项拟议的研究的目的是在一项单一的纵向研究中检验这一假设，即较高的C型应对水平通过失调艾滋病毒特异性β-趋化因子的产生而促进艾滋病毒的进展。将对至少100名艾滋病毒感染参与者进行基线生物心理社会评估(从N=200开始，以解决预期的自然减员问题，并在6、12、18、24和36个月进行心理社会措施，包括C型应对；应激和反应的心理生理措施；有证据或理论理由表明其与艾滋病毒进展相关的β-趋化因子和细胞因子的实验室措施；以及临床变量，包括CD4细胞计数、艾滋病毒-1RNA(病毒载量，VL)。仅评估的健康状况将在48个月后确定。多变量分析将检验这些措施的贡献及其相互作用，以阐明艾滋病毒进展的潜在中介因素，控制基线临床状态和抗逆转录病毒治疗。其目的是了解和描绘观察到的生物、心理和社会因素之间的关系和相互作用如何通过“宏观中介”促进艾滋病毒的进展，如已证明或假设与艾滋病毒进展有关的动态平衡控制方面的放松管制。

DESCRIPTION (provided by applicant): Significant individual differences in HIV progression suggest that psychoneuroimmunological (PNI) mechanisms are implicated. Previous and preliminary studies by the investigators have demonstrated a longitudinal relationship between the maladaptive Type C coping style (emotionally inexpressive, not recognizing own needs or feelings) and HIV progression; and a cross-sectional relationship between Type C coping and lower production of HIV-specific beta chemokines, which are ligands for the CCR5 HIV coreceptor, and associated with potent HIV inhibitory activity. The purpose of the proposed study is to test within a single longitudinal study the hypothesis that higher levels of Type C coping contribute to HIV progression through dysregulation of HIV -specific beta-chemokine production. Biopsychosocial assessments of at least 100 HIV-infected participants will be conducted at baseline (starting with N = 200 to address expected attrition, and at 6, 12, 18, 24, and 36 months on psychosocial measures, including Type C coping; psychophysiological measures of stress and reactivity; laboratory measures of beta-chemokines and cytokines for which there is evidence or theoretical rationale for their relevance to HIV progression; and clinical variables including CD4 cell count, HIV-1 RNA (viral load, VL). Medical status only assessed will be determined at 48 months. Multivariate analyses will examine the contribution of these measures and their interactions to elucidate potential mediators of HIV progression, controlling for baseline clinical status and antiretroviral therapy. The goal is to understand and delineate how observed relationships and interactions among biopsychosocial factors may contribute to HIV progression through such "macro-mediators" as deregulation in homeostatic control, which have been demonstrated or hypothesized to be related to HIV progression.