MIDCAREER INVESTIGATOR AWARD IN PATIENT ORIENTED RESEA

描述(由申请人提供)：在过去的15年里，我一直有机会在营养和最近感染艾滋病毒患者的代谢问题方面发展临床研究生涯。本次申请以患者为中心的职业生涯中期奖的目的是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受训人员。随着艾滋病毒在发达国家越来越成为一种慢性、可控的感染，确定、了解和管理艾滋病毒感染者的营养和代谢问题的能力已成为优化持续时间和生活质量的关键。虽然高效抗逆转录病毒疗法(HAART)的使用大大减少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。虽然在艾滋病流行初期，严重消瘦是艾滋病患者最常见的疾病之一，但频率有所下降，但这些患者的体重显著下降的情况仍然很常见，这种体重下降的原因和长期的医疗影响仍有待确定。随着HAART疗法的实施大大减少了艾滋病毒相关死亡和机会性疾病的数量，感染艾滋病毒并接受HAART治疗的患者的寿命(和老龄化)的增加暴露了这些患者的额外营养和代谢问题。人们越来越担心，HAART的长期副作用之一(或可能增加艾滋病毒携带者的存活率)可能包括增加心血管疾病的风险。艾滋病毒感染中心血管风险增加的可能性需要进行额外的调查，如果是真的，将需要调查以确定这种风险的病因和预测因素，以及开发干预和降低这种风险的手段。艾滋病毒的所有代谢问题背后是一个更基本的问题，即病毒的特定特征的作用和艾滋病毒慢性感染的作用，以及由此导致的慢性炎症对感染患者代谢和生理功能的影响。我希望在这个奖项的支持下，能够对这些问题做出一些澄清。此外，这个奖项将支持我在这些重要的临床研究问题上指导受训人员的能力。

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.