METABOLISM, MICRONUTRIENTS, AND ANTIRETROVIRAL THERAPY OUTCOMES IN ZAMBIA

描述（由申请人提供）：最近在撒哈拉以南非洲艾滋病毒/艾滋病感染者中大规模采用抗逆转录病毒疗法（ART），虽然挽救了许多人的生命，但也带来了很高的早期死亡率。该区域营养不良的高发率，加上艾滋病毒疾病的恶化，很可能是导致早期死亡和抗逆转录病毒治疗总体结果的一个因素。先前在资源受限环境中对艾滋病病毒感染的研究报告称，在缺乏抗逆转录病毒治疗的情况下，营养缺乏症患者的预后较差，但没有一项研究记录了抗逆转录病毒治疗对营养状况或营养状况对抗逆转录病毒治疗结果的纵向、个人影响。我们已经启动了一项试点研究，以检查在治疗和喂养严重恶病质或消瘦患者的多个环境中观察到的再喂养综合征（RS）是否导致了早期死亡。2006年11月，我们开始招募200名在赞比亚卢萨卡阿拉巴马大学伯明翰分校（UAB）传染病研究中心（CIDRZ）支持的诊所开始抗逆转录病毒治疗的患者，这些患者表现出抗逆转录病毒治疗早期死亡的高风险（CD4+计数< 50细胞/<L或体重指数< 16 kg/m2）。我们在抗逆转录病毒治疗的前3个月进行了6次有针对性的症状回顾、体格检查和饮食召回，并测量了血清中磷酸盐、钾、镁、葡萄糖和白蛋白的水平。到目前为止，12%的受试者在1次或更多次就诊时符合RS标准；19例队列死亡中有4例为RS；5例RS患者补磷后存活。R21的资助将使我们能够在已经招募的人群中监测许多额外的结果，从而显著提高我们的研究效率和成本效益。在储存的血清样本中，我们将在ART之前和ART期间测量额外的代谢分析物（钠、氯化物、碳酸氢盐、尿素氮和肌酐）、选定的微量营养素（铁蛋白用于铁状态、叶酸、维生素A、B12和E以及硒）和炎症标志物（c反应蛋白和1-1-酸糖蛋白）。我们将在6个月和12个月时进行随访，并分析饮食召回中的营养成分。这将使我们能够通过将RS与水合和电解质紊乱区分开来，更明确地诊断RS，记录ART对食物和营养摄入的影响，并检测微量营养素缺乏和流动对ART第一年预后的影响。研究结果将指导干预试验的设计，以解决代谢和营养问题，降低抗逆转录病毒治疗的早期死亡率，并在资源受限的情况下改善抗逆转录病毒治疗的结果。

DESCRIPTION (provided by applicant): The recent large-scale introduction of antiretroviral therapy (ART) among persons living with HIV/AIDS (PLWHA) in sub-Saharan Africa, while lifesaving for many, has been attended by a high early mortality rate. It is probable that the high prevalence of malnutrition in the region, worsened by HIV disease, is a factor in both early mortality and overall ART outcomes. Previous studies in PLWHA in resource-constrained settings have reported poorer outcomes in persons with nutritional deficiencies in the absence of ART, but none has documented longitudinal, within-person effects of ART on nutritional status or of nutritional status on ART outcomes. We have initiated a pilot study to examine whether the refeeding syndrome (RS), which has been observed in multiple settings in which severely cachectic or marasmic patients are treated and fed, contributes to the early deaths. In November 2006 we began recruiting 200 patients who are starting ART at a clinic supported by the University of Alabama at Birmingham's (UAB) Centre for Infectious Disease Research in Lusaka, Zambia (CIDRZ) and who exhibit high risk for early ART mortality (CD4+ count < 50 cells/<L or body mass index [BMI] < 16 kg/m2). We are conducting targeted symptom reviews, physical examinations, and dietary recalls 6 times in the first 3 months of ART, and measuring serum levels of phosphate, potassium, magnesium, glucose, and albumin. To date, 12% of subjects have met our criterion for RS at 1 or more visits; 4 of 19 cohort mortalities had RS; and 5 subjects with RS survived after phosphorus supplementation. R21 funding will enhance our study significantly and cost- efficiently by enabling us to monitor many additional outcomes in this already-recruited population. In stored serum samples we will measure additional metabolic analytes (sodium, chloride, bicarbonate, urea nitrogen, and creatinine), selected micronutrients (ferritin for iron status, folic acid, vitamins A, B12, and E, and selenium), and inflammatory markers (C-reactive protein and 1-1-acid glycoprotein) before and during ART. We will extend the study with visits at 6 and 12 months and will analyze the nutrient contents of the dietary recalls. This will enable us to diagnose RS more definitively by distinguishing it from disorders of hydration and electrolytes, to document the effects of ART on food and nutrient intakes, and to detect effects of micronutrient deficiencies and fluxes on outcomes in the first year of ART. The results will guide the design of intervention trials to address metabolic and nutritional issues, to reduce early ART mortality and improve ART outcomes in resource-constrained settings. PUBLIC HEALTH RELEVANCE: The introduction of antiretroviral therapy (ART) among persons with HIV/AIDS in sub- Saharan Africa, many of whom are undernourished, has been attended by a surprisingly high early mortality rate. This project aims to examine the influence of metabolic and micronutrient status on ART outcomes in a population in Lusaka, Zambia who are at high risk for early ART mortality. Future intervention trials will address these metabolic and nutritional issues, to reduce early ART mortality and improve ART outcomes in resource-constrained settings.