Randomized, controlled trial of daily trimethoprim-sulfamethoxazole or weekly chl

每日甲氧苄啶-磺胺甲恶唑或每周一次 Chl 的随机对照试验

• 批准号: 7511837
• 负责人: CHRISTOPHER V. PLOWE
• 金额: $ 21.65万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-08-01 至 2010-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7511837
• 关键词: AIDS-Related Opportunistic Infections; Address; Adult; Affect; Africa; Africa South of the Sahara; Anti-Bacterial Agents; Antimalarials; Applications Grants; Bacteremia; Bacterial Infections; Budgets; CD4 Lymphocyte Count; Cessation of life; Chloroquine; Clinic; Clinical; Clinical Trials; Conduct Clinical Trials; Country; Daily; Data; Disease; Drug resistance; Funding; HIV; Health Status; Immune; Infection; Infection prevention; Investigational Drugs; Label; Lead; Life; Malaria; Malaria prevention; Malawi; Manuals; Monitor; Morbidity - disease rate; Opportunistic Infections; Persons; Pharmaceutical Preparations; Play; Pneumonia; Procedures; Prophylactic treatment; Protocols documentation; Public Health; Randomized; Randomized Controlled Trials; Research; Research Ethics Committees; Resistance; Risk; Role; Safety; Training; Treatment Protocols; Trimethoprim-Sulfamethoxazole; United States Food and Drug Administration; Upper arm; Viral Load result; Writing; antimicrobial; antiretroviral therapy; authority; data management; design; drug efficacy; enteritis; evidence based guidelines; improved; mortality; prevent; protective effect; reconstitution; response; scale up; trial comparing

DESCRIPTION (provided by applicant): A daily regimen of the antibacterial drug trimethoprim-sulfamethoxazole (TS) reduces disease and death among people living with HIV in sub-Saharan Africa by preventing opportunistic infections including bacteremia, pneumonia and enteritis as well as malaria. It is not known whether this protective effect persists after immune reconstitution in HIV-infected persons receiving antiretroviral therapy (ART) or if infections prevented by TS, including malaria, influence the progression of HIV disease. With the scaling up of ART in Africa, public health authorities need to know if TS prophylaxis is necessary for those who are stable on ART. ART is associated with a dramatically reduced risk of typical AIDS-associated opportunistic infections. We therefore hypothesize that if there is a benefit of TS prophylaxis after immune reconstitution in this setting it will be due to the prevention of malaria infection, and that prophylaxis with a highly efficacious antimalarial drug (chloroquine, which now has 99% efficacy against malaria in Malawi) will be superior to daily prophylaxis with an antibacterial drug with lower antimalarial efficacy (TS, which had 80% efficacy against malaria in recent studies in Malawi). The overall public health objective of this application is to determine if TS can safely be stopped after immune reconstitution on ART. The primary research question is whether persons who are clinically stable on ART benefit from antibacterial prophylaxis, antimalarial prophylaxis, both, or neither. Secondary questions focus on understanding the role that antimicrobial prophylaxis may play in improving sustained responses to ART by preventing infections associated with rises in HIV viral load, and assessing antimalarial drug efficacy and selection for drug resistance in HIV-infected persons. To address these questions, we have designed a three-arm randomized open-label clinical trial comparing daily TS prophylaxis for prevention of malaria and bacterial infections, with weekly chloroquine prophylaxis to prevent only malaria, compared to no prophylaxis, in adults who are clinically stable after 6-12 months on ART. Under previous funding a protocol for this trial has been written and IRB approval obtained. This R34 will support completion of planning for the study and lead to submission of a U01 grant application to support the conduct of the clinical trial at the Blantyre Malaria Project Ndirande Research Clinic in Blantyre, Malawi.

描述（由申请人提供）：抗菌药物三甲氧苄啶 - 磺胺甲恶唑（TS）的每日方案可通过预防菌血症，肺炎和肺炎以及疟疾以及疾病，减少撒哈拉以南非洲艾滋病毒的疾病和死亡。尚不清楚这种保护作用在接受抗逆转录病毒疗法（ART）的HIV感染者免疫重建后是否持续存在，或者包括疟疾在内的TS预防的感染会影响HIV疾病的进展。随着非洲艺术的扩展，公共卫生当局需要知道对于那些稳定艺术的人来说，预防TS是否需要预防。 ART与典型的艾滋病相关机会感染的风险大大降低有关。因此，我们假设我们假设，如果在这种情况下免疫重建后TS预防有好处，这将是由于预防疟疾感染，并且具有高效的抗疟药（氯喹（氯喹）（氯喹（现在，马拉维在马拉匹氏症中，对疟疾）的疗效较低）将是较低的抗性药物的预防症，将会在马拉维中具有99％的疗效），这将是较低的抗议，而抗疟疾的效果将是较高的抗议，而抗疟疾的效果将是较高的，而在马拉匹属性中，毒药将有效地养成制度，而较高的抗精性却是较高的。 （TS，在马拉维最近的研究中对疟疾具有80％的疗效）。 该应用程序的总体公共卫生目标是确定在免疫建立了艺术后是否可以安全停止TS。主要的研究问题是，在临床上稳定的艺术稳定的人是否受益于抗菌预防，抗疟疾预防或两者都不是。次要问题的重点是了解抗菌预防的作用，可以通过防止与HIV病毒载量增加相关的感染以及评估抗菌药物疗效和对艾滋病毒感染者耐药性的选择，从而在改善对ART的持续反应中起作用。为了解决这些问题，我们设计了一项三臂随机开放标签临床试验，比较了预防疟疾和细菌感染的每日TS预防，每周一次，每周预防氯喹的预防，以防止疟疾，与无预防性相比，在6-12个月以后在6-12个月以前是临床稳定的。 根据以前的资助，已经编写了该试验的协议，并获得了IRB批准。该R34将支持完成研究计划的完成，并导致在马拉维Blantyre的Blantyre Malaria Project Ndirande Research Clinic的Blantyre Malaria Project Ndirande Research Clinic中提交U01赠款申请。