Multi-vitamins, HAART and HIV/AIDS in Uganda

描述(申请人提供)：抗逆转录病毒疗法逐渐成为发展中国家的护理标准，带来了巨大的好处，但艾滋病毒阳性人群中的发病率仍然很高。多种维生素补充剂具有增强免疫的作用，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的免疫状况，降低HAART前疾病阶段的发病率和死亡率。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，我们建议对相同的大剂量复合维生素补充剂(包含B-维生素、C和E)进行双盲、安慰剂对照、随机试验，以确定它们在延缓疾病进展方面的有效性，表现为CD4计数增加、体重增加和生活质量改善，并降低发病率、死亡率和与药物相关的不良事件(如周围神经病、贫血和腹泻)。我们将在乌干达的卡云加农村地区招收400名正在接受或最近发起HAART的男女。在基线和之后的每月，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况并进行研究程序。每个参与者将被跟踪18个月或直到他/她死亡或失去随访。如果参与者错过了预定的诊所预约，将进行家访。我们将在注册时和几个随访点进行营养评估(人体测量和饮食摄入量)，并每六个月进行一次实验室测量(CD4细胞计数和全血计数)。重要的是，在整个研究期间，所有研究参与者都将继续按照国家指导方针接受护理标准。复合维生素可能是一种低成本的辅助疗法，有助于减轻HAART中HIV感染者的疾病负担和提高生活质量。同时，它们的疗效可以推迟HAART改用二线方案的需要，从而有助于在发展中环境中保留有限的药物方案。我们的申请代表着哈佛公共卫生学院、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，但这些有效的挽救生命的药物已经认识到了局限性。复合维生素补充剂是一种可能的低成本辅助疗法，具有增强免疫的特性，可以减缓服用HAART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，这将有助于在艾滋病毒耐药株不断增加的情况下，在发展中国家保留有限的药物方案。 与公共卫生相关：在发展中国家广泛使用抗逆转录病毒药物正在成为现实，但这些有效的挽救生命的药物已经认识到局限性。复合维生素 补充剂代表了一种可能的低成本辅助疗法，具有增强免疫的特性，可以减缓服用HAART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，这将有助于在艾滋病毒耐药株不断增加的情况下，在发展中国家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.