MIDCAREER INVESTIGATOR AWARD IN PATIENT ORIENTED RESEA

描述（由申请人提供）：在过去的15年里，我有机会在营养和最近的HIV感染患者的代谢问题方面发展临床研究事业。本申请的目的是在以病人为导向的研究中获得职业中期奖，以促进我进行临床研究的能力，并在艾滋病毒相关研究问题的临床研究中指导学员。由于艾滋病毒在发达国家已成为一种慢性、可管理的感染，因此，确定、理解和管理艾滋病毒感染患者的营养和代谢问题的能力对于优化生命持续时间和质量至关重要。尽管高效抗逆转录病毒疗法（HAART）的使用大大降低了艾滋病毒机会性感染和死亡的频率，但艾滋病毒和HAART的长期并发症仍然很常见。虽然在流行病早期，严重消瘦是HIV感染患者中最常见的艾滋病定义疾病之一，但其发生频率已经下降，但在这些患者中发生显著体重减轻仍然很常见，并且这种体重减轻的病因和长期医学影响仍有待确定。由于HAART治疗的机构已经大大减少了HIV相关死亡的数量和机会性疾病的数量，感染HIV并接受HAART治疗的患者的寿命延长（和衰老）揭示了这些患者的额外营养和代谢问题。越来越多的人担心，HAART的长期副作用之一（或可能增加HIV生存率）可能包括心血管疾病的风险增加。艾滋病毒感染者心血管风险增加的可能性需要进一步调查，如果是真实的，将需要调查以确定这种风险的病因和预测因素，并开发干预和降低这种风险的方法。在HIV的所有代谢问题的基础上是一个更基本的问题，即病毒的特定特征的作用和HIV慢性感染的作用，以及由此产生的慢性炎症变化对感染患者的代谢和生理功能的影响。我希望能够在这个奖项的支持下对这些问题进行一些澄清。此外，该奖项将支持我在这些重要的临床研究问题上指导学员的能力。

DESCRIPTION (provided by applicant): I have had the opportunity for the last 15 years to develop a clinical research career in nutritional and more recently, metabolic issues in patients infected with HIV. The purpose of this application for a mid career award in patient oriented research is to facilitate my ability to perform clinical research and to mentor trainees in clinical research in HIV related research questions. As HIV has become more of a chronic, manageable infection in the developed world, the ability to define, understand and manage the nutritional and metabolic issues in HIV-infected patients has become critical to permit optimization of duration and quality of life. Although the use of Highly Active Antiretroviral Therapy (HAART) has dramatically reduced the frequency of opportunistic infections and death in HIV, long-term complications of HIV and HAART remain common. While the severe wasting that was one of the most frequent AIDS defining illnesses in HIV infected patients in the earlier days of the epidemic has declined in frequency, the occurrence of significant weight loss has continued to be common in these patients and the etiologies and long term medical impact of this weight loss remains to be determined. As the institution of HAART therapy has dramatically reduced the number of HIV-associated deaths and the numbers of opportunistic illnesses, the increased life span (and aging) of patients infected with HIV and treated with HAART has revealed additional nutritional and metabolic issues in these patients. There is increasing concern that one of the long-term side effects of HAART (or potentially the increased survival with HIV) may include an increased risk for cardiovascular disease. The potential for increased cardiovascular risk in HIV infection requires additional investigation and if real, will require investigations to define the etiology and predictors of this risk as well as the development of means to intervene and reduce this risk. Underlying all of the metabolic issues in HIV is a more basic question, that is, the role of the specific characteristics of the virus and the role of chronic infection with HIV, and the resulting chronic inflammatory changes on metabolic and physiological function in infected patients. I hope to be able to work toward some elucidation of these issues with the support of this award. In addition, this award will support my ability to mentor trainees in these important clinical research questions.