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）：抗菌药物甲氧苄氨嘧啶-磺胺甲恶唑 (TS) 的每日治疗方案可通过预防包括菌血症、肺炎、肠炎以及疟疾在内的机会性感染，减少撒哈拉以南非洲艾滋病毒感染者的疾病和死亡。目前尚不清楚接受抗逆转录病毒治疗 (ART) 的 HIV 感染者的免疫重建后这种保护作用是否持续存在，或者 TS 预防的感染（包括疟疾）是否会影响 HIV 疾病的进展。随着非洲抗逆转录病毒疗法的推广，公共卫生当局需要知道对于那些接受抗逆转录病毒疗法病情稳定的人是否有必要进行 TS 预防。 ART 可以显着降低典型艾滋病相关机会性感染的风险。因此，我们假设，如果在这种情况下免疫重建后进行 TS 预防有好处，那将是由于预防疟疾感染，并且使用高效抗疟药物（氯喹，目前在马拉维对疟疾有 99% 的功效）进行预防将优于使用抗疟功效较低的抗菌药物进行日常预防 （TS，在马拉维最近的研究中对疟疾有 80% 的功效）。 本申请的总体公共卫生目标是确定在 ART 免疫重建后是否可以安全地停止 TS。主要的研究问题是，接受 ART 治疗后临床表现稳定的人是否能从抗菌预防、抗疟预防、两者都受益或两者都不受益。次要问题集中于了解抗菌药物预防在通过预防与 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，并评估抗疟药物的疗效和 HIV 感染者耐药性的选择。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 6-12 个月后临床稳定的成年人中，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与不预防相比。 在之前的资助下，该试验的方案已经编写并获得了 IRB 的批准。该 R34 将支持完成研究规划，并导致提交 U01 拨款申请，以支持在马拉维布兰太尔的布兰太尔疟疾项目 Ndirande 研究诊所进行临床试验。