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）：抗菌药物甲氧苄啶-磺胺甲恶唑（TS）的每日方案通过预防机会性感染（包括菌血症、肺炎和肠炎以及疟疾），减少撒哈拉以南非洲艾滋病毒感染者的疾病和死亡。目前尚不清楚这种保护作用是否在接受抗逆转录病毒治疗（ART）的HIV感染者免疫重建后持续存在，或者TS预防的感染（包括疟疾）是否会影响HIV疾病的进展。随着抗逆转录病毒疗法在非洲的推广，公共卫生当局需要知道，对于那些稳定接受抗逆转录病毒疗法的人，TS预防是否有必要。因此，我们假设，如果在这种情况下免疫重建后TS预防有益处，那将是由于预防疟疾感染，并且使用高效抗疟药物预防（氯喹，目前在马拉维对疟疾有99%的疗效）将上级抗疟疗效较低的抗菌药物每日预防（TS，在马拉维最近的研究中对疟疾有80%的疗效）。 本申请的总体公共卫生目标是确定TS在ART免疫重建后是否可以安全地停止。主要研究问题是ART临床稳定的人是否受益于抗菌预防、抗疟预防或两者兼而有之。次要问题集中在了解抗菌预防在通过预防与HIV病毒载量上升相关的感染来改善对ART的持续反应方面可能发挥的作用，以及评估抗疟药物的疗效和HIV感染者的耐药性选择。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，在接受ART治疗6-12个月后临床稳定的成人中比较每日TS预防预防疟疾和细菌感染，每周氯喹预防仅预防疟疾。 根据先前的资助，已经编写了本试验的方案，并获得了IRB的批准。该R34将支持完成研究计划，并导致提交U 01资助申请，以支持在马拉维布兰太尔的布兰太尔疟疾项目Ndirande研究诊所开展临床试验。