Elucidating Biopsychosocial Mediators of HIV Progression

描述（由申请人提供）：HIV进展的显著个体差异表明涉及心理神经免疫学（PNI）机制。研究人员先前和初步的研究表明，适应不良的C型应对方式（情感上缺乏表达，不认识自己的需要或感受）与艾滋病毒进展之间存在纵向关系；以及C型应对与HIV特异性β趋化因子较低产生之间的横断面关系，β趋化因子是CCR5 HIV辅助受体的配体，与有效的HIV抑制活性相关。本研究的目的是在一项单一的纵向研究中检验高水平的C型应对通过失调HIV特异性趋化因子的产生而促进HIV进展的假设。将在基线（从N = 200开始，以解决预期的消耗问题）对至少100名艾滋病毒感染者进行生物心理社会评估，并在6、12、18、24和36个月进行心理社会测量，包括C型应对；压力和反应性的心理生理测量；有证据或理论依据证明与艾滋病毒进展相关的-趋化因子和细胞因子的实验室测量；和临床变量包括CD4细胞计数，HIV-1 RNA（病毒载量，VL）。只有在48个月时才能确定经评估的健康状况。多变量分析将检查这些措施的贡献及其相互作用，以阐明HIV进展的潜在介质，控制基线临床状态和抗逆转录病毒治疗。目的是了解和描述观察到的生物心理社会因素之间的关系和相互作用如何通过“宏观介质”（如体内平衡控制的放松）促进艾滋病毒的进展，这些“宏观介质”已被证明或假设与艾滋病毒的进展有关。

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.