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的艾滋病毒/艾滋病（PLWHA）感染者中大规模引入抗逆转录病毒疗法（ART），虽然挽救了许多人的生命，但早期死亡率很高。该地区营养不良的高流行率，加上艾滋病毒疾病的恶化，很可能是造成早期死亡率和总体抗逆转录病毒治疗结果的一个因素。以前在资源有限的环境中对艾滋病毒感染者和艾滋病患者的研究报告了在没有抗逆转录病毒治疗的情况下营养缺乏者的不良结局，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局的纵向、人内影响。我们已经启动了一项试点研究，以检查是否再喂养综合征（RS），这已被观察到在多个设置中，严重恶病质或消瘦患者的治疗和喂养，有助于早期死亡。2006年11月，我们开始招募200名患者，这些患者在由亚拉巴马大学伯明翰分校（UAB）赞比亚卢萨卡传染病研究中心（CIDRZ）支持的诊所开始接受ART治疗，并表现出早期ART死亡的高风险（CD 4+计数< 50个细胞/<L或体重指数[BMI] < 16 kg/m2）。我们正在进行有针对性的症状审查，体格检查，并在ART的前3个月进行6次饮食召回，并测量磷酸盐，钾，镁，葡萄糖和白蛋白的血清水平。迄今为止，12%的受试者在1次或多次访视时符合我们的RS标准; 19例队列死亡中有4例患有RS; 5例RS受试者在补充磷后存活。R21资金将使我们能够监测这一已招募人群的许多额外结果，从而显着且具有成本效益地增强我们的研究。在储存的血清样本中，我们将测量其他代谢分析物（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），和炎症标记物（C-反应蛋白和1-1-酸性糖蛋白）我们将延长研究，在6个月和12个月时进行访视，并分析饮食回忆的营养成分。这将使我们能够通过将RS与水化和电解质紊乱区分开来来更明确地诊断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通量对ART第一年结果的影响。结果将指导干预试验的设计，以解决代谢和营养问题，降低早期ART死亡率，改善资源有限环境下的ART结果。 公共卫生相关性：在撒哈拉以南非洲，艾滋病毒/艾滋病患者中有许多人营养不良，在对他们采用抗逆转录病毒疗法后，早期死亡率高得惊人。该项目旨在研究代谢和微量营养素状况对赞比亚卢萨卡一群早期抗逆转录病毒疗法死亡率高风险人群抗逆转录病毒疗法结果的影响。未来的干预试验将解决这些代谢和营养问题，以降低早期ART死亡率并改善资源有限环境中的ART结局。

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.