Adjunct Vitamin A Therapy for Tuberculosis and HIV/AIDS

描述（由申请人提供）：结核病是全世界死亡的主要原因之一，估计每年造成300万人死亡。微量营养素缺乏症在艾滋病毒感染和肺结核期间很常见，而微量营养素缺乏症与免疫力受损、发病率和死亡率增加有关。尽管对结核病进行了充分的化疗，但感染艾滋病毒的成人肺结核的发病率和死亡率仍然极高。这项正在进行的III期随机、双盲、对照临床试验的目的是确定每日补充多种维生素（维生素和矿物质）是否可以降低马拉维艾滋病毒感染的成年肺结核患者的发病率和死亡率。根据马拉维国家结核病控制规划，所有参与者接受标准结核病化疗8个月，试验中的随访总持续时间为24个月。该试验有一个社区咨询委员会，由当地社区成员和参与者组成。该试验的原始样本量减少到500名HIV感染的成年人，以便在研究期间完成招募并应对预算削减。NIH的NIAID HIV治疗性临床试验数据和安全监测委员会（DSMB）进行的中期分析显示，该试验的入组稳定，对补充剂的依从性良好，随访率高。DSMB建议将本试验的样本量增加至至少80%的把握度，以检测死亡率降低20%。为了满足这一建议，我们建议将样本量增加到840例艾滋病毒感染的成年肺结核患者。该试验还包括300名患有肺结核的艾滋病毒阴性成年人，以减少污名化。如果这项研究表明，多种维生素补充剂可以降低艾滋病毒感染的成人肺结核的发病率和死亡率，这种适当的，低成本的干预措施可以与结核病治疗相结合，以改善发展中国家艾滋病毒感染者的健康和生存。

DESCRIPTION (provided by applicant): Tuberculosis is one of the leading causes of mortality worldwide, accounting for an estimated three million deaths annually. Micronutrient deficiencies are common during HIV infection and during pulmonary tuberculosis, and micronutrient deficiencies are associated with impaired immunity and increased morbidity and mortality. Despite adequate chemotherapy for tuberculosis, the morbidity and mortality of HIV-infected adults with pulmonary tuberculosis remains extremely high. The goal of this ongoing Phase III randomized, double-blind, controlled clinical trial is to determine whether a daily multivitamin (vitamins and minerals) supplement can reduce morbidity and mortality of HIV-infected adults with pulmonary tuberculosis in Malawi. All participants receive standard tuberculosis chemotherapy for eight months as per the Malawi National Tuberculosis Control Programme, and the total duration of follow-up in the trial is twenty-four months. The trial has a Community Advisory Board which consists of local community members and participants. The original sample size of the trial was reduced to 500 HIV-infected adults in order to complete enrollment within the study period and deal with a budget reduction. Interim analyses conducted for the NIAID HIV Therapeutic Clinical Trials Data and Safety Monitoring Board (DSMB) at NIH show that the trial has been conducted with steady enrollment, good adherence to supplementation, and high follow-up. The DSMB has recommended that the sample size of this trial be increased to have at least 80% power to detect a 20% reduction in mortality. To meet this recommendation, we propose to increase the sample size to 840 HIV-infected adults with pulmonary tuberculosis. The trial also includes 300 HIV-negative adults with pulmonary tuberculosis in order to reduce stigmatization. If this study demonstrates that a multivitamin supplement can reduce morbidity and mortality of HIV-infected adults with pulmonary tuberculosis, this appropriate, low cost intervention could be integrated with tuberculosis treatment to improve health and survival of HIV-infected individuals in developing countries.