METABOLISM, MICRONUTRIENTS, AND ANTIRETROVIRAL THERAPY OUTCOMES IN ZAMBIA

赞比亚的新陈代谢、微量营养素和抗逆转录病毒治疗结果

• 批准号: 8140699
• 负责人: DOUGLAS CORBETT HEIMBURGER
• 金额: $ 8.5万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-30 至 2012-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8140699
• 关键词: AIDS/HIV problem; Accounting; Acids; Acquired Immunodeficiency Syndrome; Address; Adult; Adverse effects; Affect; Africa South of the Sahara; Alabama; Albumins; Anemia; Bicarbonates; Body Weight decreased; Body mass index; C-reactive protein; CD4 Lymphocyte Count; Carbohydrates; Cardiopulmonary; Caring; Cells; Cessation of life; Child; Clinic; Clinical; Clinical Trials; Complex; Country; Creatinine; Data; Desire for food; Development; Diagnosis; Diarrhea; Dietary intake; Disease; Disease Progression; Drug toxicity; Edema; Electrolyte Balance; Electrolytes; Enrollment; Exhibits; Failure; Ferritin; Flare; Folic Acid; Food; Funding; Future; Gastroenteritis; Glucose; Glycoproteins; Grant; HIV; High Prevalence; Hydration status; Hypokalemia; Hypophosphatemia; Immune; Incidence; Infection; Infectious Diseases Research; Inflammation; Inflammatory; Intake; Intervention; Intervention Trial; Investigation; Iron; L Cells; Life; Magnesium; Malaria; Malnutrition; Measures; Metabolic; Metabolism; Micronutrients; Monitor; Nutrient; Nutritional; Nutritional status; Opportunistic Infections; Outcome; Patients; Persons; Phosphorus; Physical Examination; Pilot Projects; Population; Potassium Phosphate; Probability; Recruitment Activity; Reporting; Research; Resources; Risk Factors; Sampling; Selenium; Serum; Signs and Symptoms; Sodium Chloride; Staging; Supplementation; Symptoms; Syndrome; Testing; Time; United States National Institutes of Health; Universities; Urea Nitrogen; Vertical Disease Transmission; Villous Atrophy; Viral Load result; Visit; Vitamin A; Vomiting; Weight Gain; Zambia; absorption; antiretroviral therapy; base; cohort; cost; design; feeding; high risk; immune function; improved; inflammatory marker; inorganic phosphate; meetings; micronutrient deficiency; mortality; public health relevance; reconstitution; response; therapy outcome; transmission process; wasting

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.

描述（由申请人提供）：最近在撒哈拉以南非洲享有艾滋病毒/艾滋病（PLWHA）的人中，最近大规模引入了抗逆转录病毒疗法（ART），虽然为许多人进行救生，但已有很高的早期死亡率参加。艾滋病毒疾病恶化的该地区营养不良的高流行率很可能是早期死亡率和整体艺术结局的一个因素。先前在资源受限环境中对PLWHA的研究报告说，在没有艺术的情况下，营养缺乏的人的结局较差，但没有一个记录艺术对营养状况的纵向，人身内部对营养状况或营养状况对艺术成果的影响。我们已经开始了一项试点研究，以检查在多种环境中观察到的重喂养综合征（RS）是否会受到严重缓存或Marasmic患者的治疗和喂养，这会导致早期死亡。 2006年11月，我们开始招募200名在阿拉巴马大学（UAB）在赞比亚卢萨卡（Cidrz）的伯明翰大学（UAB）传染病研究中心支持的诊所中开始艺术的患者。我们正在进行有针对性的症状综述，体格检查和饮食中的饮食召回，在艺术的前三个月中，我们进行了6次，并测量磷酸盐，钾，镁，葡萄糖和白蛋白的血清水平。迄今为止，有12％的受试者符合我们在1次或更多访问的Rs的标准； 19个队列死亡中的4个中有卢比；和5名RS的受试者在补充磷后存活。 R21的资金将通过使我们能够监视已经获得的人群中的许多其他结果，从而大大增强我们的研究。 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.我们将在6个月和12个月的时间进行访问扩展研究，并将分析饮食召回的营养含量。这将使我们能够通过将其与水合和电解质的疾病区分开来更明确地诊断RS，以记录艺术对食物和营养摄入量的影响，并检测微量营养素的缺陷和助剂对第一年美术时期的影响。结果将指导干预试验的设计，以解决代谢和营养问题，以减少早期艺术死亡率并改善资源约束环境中的艺术成果。 公共卫生相关性：在撒哈拉以南非洲的艾滋病毒/艾滋病患者中引入抗逆转录病毒疗法（ART），其中许多人的营养不足，已经出人意料地出现在早期的早期死亡率上。该项目旨在研究代谢和微量营养素地位对赞比亚卢萨卡人口的艺术成果的影响，他们处于早期艺术死亡率的高风险。未来的干预试验将解决这些代谢和营养问题，以降低早期艺术死亡率并改善资源受限环境中的艺术成果。

项目成果

Serum phosphate predicts early mortality in adults starting antiretroviral therapy in Lusaka, Zambia: a prospective cohort study.

• DOI: 10.1371/journal.pone.0010687
• 发表时间: 2010-05-18
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Heimburger DC;Koethe JR;Nyirenda C;Bosire C;Chiasera JM;Blevins M;Munoz AJ;Shepherd BE;Potter D;Zulu I;Chisembele-Taylor A;Chi BH;Stringer JS;Kabagambe EK
• 通讯作者: Kabagambe EK