Multi-vitamins, HAART and HIV/AIDS in Uganda

描述（由申请人提供）：抗逆转录病毒疗法逐渐成为发展中国家的标准治疗方法，带来了巨大的益处，但在艾滋病毒阳性人群中仍存在大量发病率。多种维生素补充剂具有免疫增强作用，高剂量补充剂被发现可以改善艾滋病毒阳性坦桑尼亚妇女在HAART前阶段的免疫状态，降低发病率和死亡率。高剂量的这些补充剂被认为是在艾滋病毒感染的情况下恢复足够的营养水平所必需的。因此，我们提出了一个双盲，安慰剂对照，随机试验相同的高剂量的多种维生素补充剂（含有B族维生素，C和E），以确定其在减缓疾病进展，增加CD4计数，体重增加，改善生活质量，降低发病率，死亡率，和药物相关的不良事件（即周围神经病变，贫血和腹泻）的疗效。我们将在乌干达的农村卡永加地区招募400名正在接受或最近开始接受HAART治疗的男性和女性。在基线和此后每月，两个研究诊所的研究医生和护士将评估每名受试者的临床状态并进行研究程序。每名受试者将接受18个月的随访，或直至其死亡或失访。如果受试者错过了预定的门诊预约，将进行家访。我们将在入组和几个随访点进行营养评估（人体测量和饮食摄入），并每六个月进行一次实验室测量（CD4细胞计数和全血细胞计数）。重要的是，所有研究参与者将在整个研究期间根据国家指南继续接受标准治疗。多维生素可能是一种低成本的辅助治疗，有助于减轻疾病负担和提高艾滋病毒感染者的生活质量的HAART。与此同时，它们的功效可以通过推迟转换到HAART二线方案的需要来帮助在发展中环境中保留有限的药物方案。我们的申请代表了哈佛公共卫生学院、沃尔特里德项目和乌干达坎帕拉的马凯雷雷大学之间的合作。抗逆转录病毒药物在发展中国家的广泛使用正在成为现实，但这些有效的救命药物也有其局限性。复合维生素补充剂代表了一种可能的低成本，辅助治疗与免疫增强性能，可以减缓艾滋病毒感染者的HAART疾病进展。特别是，多种维生素可能会带来重要的临床益处，这将有助于在发展中国家保持有限的药物治疗方案，以应对日益增加的病毒耐药性HIV毒株。 公共卫生相关性：抗逆转录病毒药物在发展中国家的广泛使用正在成为现实，但这些有效的救命药物也有其局限性。多种维他命 补充剂代表了一种可能的低成本、具有免疫增强特性的辅助疗法，可以减缓接受HAART的HIV感染者的疾病进展。特别是，多种维生素可能会带来重要的临床益处，这将有助于在发展中国家保持有限的药物治疗方案，以应对日益增加的病毒耐药性HIV毒株。

DESCRIPTION (provided by applicant): Antiretroviral therapy, gradually becoming the standard of care in developing countries, confers enormous benefits and yet substantial morbidity remains in HIV-positive populations. Multivitamin supplements have immune-enhancing effects, and high-dose supplements were found to improve immunologic status and reduce morbidity and mortality among HIV-positive Tanzanian women in pre-HAART stages of disease. High doses of these supplements are thought to be required to restore adequate nutrient levels in the context of HIV infection. Therefore, we propose a double-blind, placebo- controlled, randomized trial of the same high-dose multivitamin supplements (containing B-vitamins, C, and E) to determine their efficacy in slowing disease progression, indicated by increased CD4 count, weight gain, and improved quality of life, and decreased morbidity, mortality, and drug-related adverse events (i.e. peripheral neuropathy, anemia, and diarrhea). We will enroll 400 men and women in the rural Kayunga district of Uganda, who are receiving or have recently initiated HAART. At baseline and monthly thereafter, research physicians and nurses at two study clinics will assess each participant's clinical status and undertake study procedures. Each participant will be followed for 18 months or until his /her death or loss to follow-up. Home visits will be conducted if participants miss their scheduled clinic appointments. We will perform nutritional assessments (anthropometry and dietary intake) at enrollment and several follow-up points, and laboratory measurements (CD4 cell counts and complete blood counts) every six months. Importantly, all study participants will continue receiving the standard of care according to national guidelines for the entire study period. Multivitamins could be a low-cost, adjunct therapy for helping to alleviate disease burden and elevate quality of life in HIV-infected individuals on HAART. At the same time, their efficacy could help preserve limited drug regimens in developing settings by postponing the need for switches to second line regimens of HAART. Our application represents collaboration between the Harvard School of Public Health, Walter Reed Program and Makerere University in Kampala, Uganda. The widespread use of antiretroviral drugs in developing settings is becoming a reality, yet these potent, life-saving drugs have recognized limitations. Multivitamin supplements represent a possible low-cost, adjunct therapy with immune-enhancing properties that could slow disease progression among HIV-infected individuals on HAART. In particular, multivitamins might confer important clinical benefits that would help preserve limited drug regimens in developing countries amidst increasing viral resistant HIV strains. PUBLIC HEALTH RELEVANCE: The widespread use of antiretroviral drugs in developing settings is becoming a reality, yet these potent, life-saving drugs have recognized limitations. Multivitamin supplements represent a possible low-cost, adjunct therapy with immune-enhancing properties that could slow disease progression among HIV-infected individuals on HAART. In particular, multivitamins might confer important clinical benefits that would help preserve limited drug regimens in developing countries amidst increasing viral resistant HIV strains.