Bone and fat cross-talk in antiretroviral therapy (ART) treated HIV patients

项目摘要/摘要 联合抗逆转录病毒疗法(CART)的广泛使用显著延长了人的寿命 艾滋病毒携带者(PLWH)由于艾滋病毒已经成为一种慢性病，人们越来越关注 患多种合并症的风险不成比例。在我们的家长奖中，我们关注的是两个并存问题 这在接受CART治疗的PLWH患者中发生的患病率更高-骨丢失和脂肪增加。我们的建议侧重于 抗逆转录病毒药物在这两种疾病发展中的作用并利用了一种新的临床前小鼠 HIV感染和CART治疗的模型和来自NIH资助的大规模队列的人类受试者数据 PLWH的研究。目前的行政副刊寻求利用这些正在进行的研究来扩展我们的 致力于疼痛研究，并为未来的科学方向产生支持性证据 疼痛研究。具体地说，我们试图调查肌肉骨骼疼痛，这是一种常见的 PLWH患者报告的结果研究。我们将利用我们正在进行的动物工作来调查 生物机制(目标1)和我们与MWCCS的持续合作，以获得联合定义- 艾滋病毒感染妇女肌肉骨骼疼痛的具体模式(目标2)。如果成功，补充的 AIMS将产生关于肌肉骨骼疼痛的流行率和潜在风险因素的令人兴奋的新数据 为临床疼痛的进一步研究提供经验和初步数据 在这个脆弱的人群中的机制。重要的是，补充目标与以下几个领域保持一致 NIAMS内的科学兴趣，包括专注于疼痛的免疫机制，制作大量数据 与疼痛研究相关的集合，并利用现有数据集对疼痛进行二次分析 研究。

Project Summary / Abstract The widespread use of combination antiretroviral therapy (cART) has significantly increased the lifespan of people living with HIV (PLWH). As HIV has become a chronic disease, there is a growing concern of the disproportionate risk of a variety of comorbidities. In our parent award, we are focused on two comorbidities that occur at a higher prevalence in cART treated PLWH - bone loss and fat gain. Our proposal focuses on the contribution of antiretrovirals to the development of these two conditions and utilizes a novel preclinical mouse model of HIV infection and cART treatment and human subjects data from a large-scale NIH-funded cohort study of PLWH. The current administrative supplement seeks to leverage these ongoing studies to extend our efforts into pain research and to generate supporting evidence towards a future scientific direction in pain research. Specifically, we seek to investigate musculoskeletal pain, which is a common concern of PLWH in patient reported outcome studies. We will leverage our ongoing animal work to investigate the biological mechanisms (Aim 1) and our ongoing collaboration with the MWCCS to obtain define the joint- specific patterns of musculoskeletal pain in women living with HIV (Aim 2). If successful, the supplemental aims will generate exciting new data on the prevalence and potential risk factors for musculoskeletal pain development in PLWH and provide the PI with experience and preliminary data to further research pain mechanisms in this vulnerable population. Importantly, the supplemental aims align with several areas of scientific interest within NIAMS, including focusing on immune mechanisms of pain, making large data sets relevant to pain research, and leveraging existing datasets for secondary analysis for pain research.