METABOLISM, MICRONUTRIENTS, AND ANTIRETROVIRAL THERAPY OUTCOMES IN ZAMBIA

描述(申请人提供)：最近在撒哈拉以南非洲的艾滋病毒/艾滋病患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，但伴随着较高的早期死亡率。该地区营养不良的高度流行，加上艾滋病毒疾病的恶化，很可能是导致早期死亡和整体抗逆转录病毒治疗结果的一个因素。之前在PLWHA上进行的资源受限环境下的研究报告了在没有ART的情况下营养缺乏者的预后较差，但没有一项研究记录了ART对营养状况或营养状况对ART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软体病患者的多个环境中观察到的再喂养综合征(RS)是否导致早期死亡。2006年11月，我们开始招募在赞比亚卢萨卡阿拉巴马大学伯明翰分校传染病研究中心支持的一家诊所开始抗逆转录病毒治疗的200名患者，他们表现出早期抗逆转录病毒治疗死亡的高风险(CD_4+细胞计数50细胞/t；L或体重指数16公斤/平方米)。我们在ART的前3个月进行了6次有针对性的症状评估、体检和饮食召回，并测量了血清中磷、钾、镁、葡萄糖和白蛋白的水平。到目前为止，12%的受试者在一次或多次就诊时达到了我们的RS标准；19名队列死亡患者中有4人患有RS；5名RS患者在补充磷后存活。R21资助将使我们能够监测这一已经招募的人群中的许多额外结果，从而显著地和成本效益地加强我们的研究。在储存的血清样本中，我们将在抗逆转录病毒治疗前和治疗期间检测额外的代谢分析(钠、氯、碳酸氢盐、尿素氮和肌酐)、选定的微量营养素(铁状态的铁蛋白、叶酸、维生素A、B12和E以及硒)以及炎症标志物(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个月时进行访问，并将分析饮食召回的营养成分。这将使我们能够更明确地诊断RS，将其与水合和电解质紊乱区分开来，记录ART对食物和营养摄入的影响，并在ART的第一年检测微量营养素缺乏和通量对预后的影响。这些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，并在资源有限的情况下改善ART结果。 与公共卫生相关：在撒哈拉以南非洲的艾滋病毒/艾滋病患者中采用抗逆转录病毒疗法(ART)，其中许多人营养不良，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个早期ART死亡风险较高的人群的抗逆转录病毒治疗结局的影响。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，并在资源有限的情况下改善ART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.