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护理，带来了巨大的好处，但在艾滋病毒阳性人群中仍然存在大量发病率。多种维生素补充剂具有增强免疫力的作用，发现高剂量补充剂可以改善艾滋病毒阳性的坦桑尼亚妇女在haart前疾病阶段的免疫状况并降低发病率和死亡率。人们认为，在艾滋病毒感染的情况下，需要高剂量的这些补充剂来恢复足够的营养水平。因此，我们提出了一项双盲、安慰剂对照、随机试验，研究相同的高剂量复合维生素补充剂（含有b族维生素、C和E），以确定其在减缓疾病进展方面的功效，表现为增加CD4计数、体重增加、改善生活质量、降低发病率、死亡率和药物相关不良事件（即周围神经病变、贫血和腹泻）。我们将在乌干达Kayunga地区的农村地区招募400名正在接受或最近开始了HAART治疗的男女。在基线和之后的每个月，两个研究诊所的研究医生和护士将评估每个参与者的临床状态并进行研究程序。每位参与者将被跟踪18个月或直到他/她死亡或失去随访。如参加者错过预约的门诊时间，将会进行家访。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，所有研究参与者在整个研究期间将继续按照国家指南接受标准护理。复合维生素可能是一种低成本的辅助疗法，有助于减轻接受HAART治疗的艾滋病毒感染者的疾病负担，提高他们的生活质量。同时，它们的功效可以通过推迟切换到HAART的二线方案的需要，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大学公共卫生学院、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，然而这些有效的救命药物具有公认的局限性。多种维生素补充剂可能是一种低成本的辅助疗法，具有增强免疫的特性，可以减缓接受HAART治疗的艾滋病毒感染者的疾病进展。特别是，复合维生素可能会带来重要的临床益处，这将有助于发展中国家在不断增加的病毒耐药HIV毒株中保留有限的药物方案。

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.