Clinical trial of trimethoprim-sulfamethoxazole or chloroquine in adults on ART

甲氧苄啶-磺胺甲恶唑或氯喹在成人 ART 治疗中的临床试验

• 批准号: 8985328
• 负责人: Miriam K. Laufer
• 金额: $ 39.44万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-08-01 至 2018-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8985328
• 关键词: AIDS/HIV problem; Acquired Immunodeficiency Syndrome; Address; Adult; Affect; Africa; Africa South of the Sahara; African; Antimalarials; Bacteremia; CD4 Lymphocyte Count; Caring; Cells; Chloroquine; Chloroquine resistance; Clinical; Clinical Trials; Consultations; Contractor; Cotrimoxazole; Country; Disease; Drug resistance; Ensure; Funding; Future; HIV; HIV Infections; Health; Immune; Immunologics; Incidence; Infection; Infection prevention; Institutional Review Boards; Instruction; Laboratories; Life; Malaria; Malaria prevention; Malawi; Maryland; Measures; Monitor; Morbidity - disease rate; NIH Office of AIDS Research; National Institute of Allergy and Infectious Disease; Opportunistic Infections; Organism; Parasites; Patients; Peer Review; Persons; Play; Pneumonia; Policies; Population; Prevention strategy; Principal Investigator; Prophylactic treatment; Protocols documentation; Public Health; Randomized; Relative (related person); Research; Research Design; Resistance; Risk; Role; Site; Sulfamethoxazole; Teleconferences; Time; Trimethoprim-Sulfamethoxazole; Universities; Viral; Viral Load result; Withdrawal; Work; antimicrobial; antiretroviral therapy; arm; authority; base; co-infection; data management; design; enteritis; evidence based guidelines; innovation; meetings; mortality; open label; prevent; reconstitution; response; safety study; scale up; trial comparing

DESCRIPTION (provided by applicant): Clinicians and policymakers responsible for the care of people living with HIV in Africa lack evidence to guide decisions about whether and when to stop antimicrobial prophylaxis with trimethroprim-sulfamethoxazole (TS, co-trimoxazole) in patients who are on antiretroviral therapy (ART). Moreover, the relative importance of preventing malaria, and the extent to which any benefit of TS prophylaxis in the context of ART is due to malaria prevention, are also unknown. The overall public health objective of this clinical trial is to determine the benefit, if any, of continued TS prophylaxis after ART has been successfully initiated, and whether any such benefit is due to preventing HlV-associated opportunistic infections, malaria, or both. To address these questions, we have designed a three-arm, randomized, open-label clinical trial comparing daily TS prophylaxis for prevention of malaria and HlV-associated opportunistic infections, with weekly chloroquine prophylaxis to prevent only malaria, compared to no prophylaxis, in adults with undetectable HIV viral load and a CD4 count of >250 cells/mm3 who initiated ART within two years. The innovative study design is based in part on our observation that chloroquine-resistant malaria has disappeared from Malawi following its withdrawal from use, making it an ideal agent for malaria-specific prophylaxis. The study will allow us to determine whether persons on ART with undetectable viral load benefit from antimalarial prophylaxis, antimicrobial prophylaxis to prevent HlV-associated opportunistic infections, both, or neither. Secondary objectives focus on understanding the role that antimicrobial prophylaxis may play in maintaining viral suppression and immunologic improvement on ART, assessing the efficacy of prophylaxis in the context of highly resistant organisms, and measuring the effect of prophylaxis on the selection of drug resistance in HIV-infected persons. This research aligns directly with the strategy prioritized by the NIH Office of AIDS Research to 1) determine the optimal timing for discontinuing prophylaxis for different opportunistic infections and coinfections and 2) to evaluate strategies for prevention of prevalent opportunistic and endemic infections in the context of HIV infection. RELEVANCE (See instructions): Results of this study will be of direct and immediate relevance to decision-makers in Malawi and the region, affecting the health of millions of current and future ART recipients by providing evidence to determine 1) whether to stop TS prophylaxis in persons on ART; and 2) the importance of preventing HlV-associated opportunistic infections and malaria in persons who are stable on ART. RELEVANCE (provided by applicant): Results of this study will be of direct and immediate relevance to decision-makers in Malawi and the region, affecting the health of millions of current and future ART recipients by providing evidence to determine 1) whether to stop TS prophylaxis in persons on ART; and 2) the importance of preventing HlV-associated opportunistic infections and malaria in persons who are stable on ART.

描述（由申请人提供）：负责照顾非洲艾滋病毒感染者的临床医生和政策制定者缺乏证据来指导决定是否以及何时停止对正在接受治疗的患者使用甲氧苄啶-磺胺甲恶唑（TS，复方新诺明）进行抗菌预防。抗逆转录病毒治疗（ART）。此外，预防疟疾的相对重要性，以及 ART 背景下 TS 预防的任何益处在多大程度上归因于预防疟疾，也尚不清楚。该临床试验的总体公共卫生目标是确定成功启动 ART 后继续进行 TS 预防的益处（如果有的话），以及任何此类益处是否归因于预防 HIV 相关机会性感染、疟疾或两者。为了解决这些问题，我们设计了一项三臂、随机、开放标签的临床试验，比较每日 TS 预防预防疟疾和 HIV 相关机会性感染与每周氯喹预防仅预防疟疾与不预防相比， HIV 病毒载量不可检测且 CD4 计数 >250 个细胞/mm3 且在两年内开始 ART 的成人。这项创新研究设计部分基于我们的观察，即耐氯喹疟疾在停止使用后已在马拉维消失，使其成为疟疾特异性预防的理想药物。这项研究将使我们能够确定病毒载量无法检测到的接受 ART 治疗的患者是否受益于抗疟疾预防、抗菌药物预防以预防 HIV 相关机会性感染，或者两者都受益。次要目标侧重于了解抗菌药物预防在维持 ART 病毒抑制和免疫学改善方面可能发挥的作用，评估在高耐药微生物背景下预防的有效性，并测量预防对 HIV 耐药性选择的影响。感染者。这项研究与 NIH 艾滋病研究办公室优先考虑的战略直接一致，即 1）确定停止预防不同机会性感染和合并感染的最佳时机，2）评估艾滋病毒背景下预防流行机会性和地方性感染的策略感染。相关性（参见说明）：本研究的结果将与马拉维和该地区的决策者直接相关，通过提供证据来确定 1) 是否停止 TS 预防，从而影响数百万当前和未来 ART 接受者的健康接受 ART 治疗的人； 2) 对于接受抗逆转录病毒疗法病情稳定的人来说，预防艾滋病毒相关机会性感染和疟疾的重要性。 相关性（由申请人提供）：这项研究的结果将与马拉维和该地区的决策者直接相关，通过提供证据来确定 1) 是否停止 TS，从而影响数百万当前和未来 ART 接受者的健康接受抗逆转录病毒疗法的人进行预防； 2) 对于接受抗逆转录病毒疗法病情稳定的人来说，预防艾滋病毒相关机会性感染和疟疾的重要性。