Addressing the burden of untreated HIV in cancer patients in sub-Saharan Africa: feasibility and planning for a pragmatic clinical trial

解决撒哈拉以南非洲癌症患者未经治疗的艾滋病毒负担：实用临床试验的可行性和规划

• 批准号: 10379415
• 负责人: Rachel Ann Bender Ignacio
• 金额: $ 16.79万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-04-01 至 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10379415
• 关键词: AIDS related cancer; Acquired Immunodeficiency Syndrome; Address; Adult; Adverse event; Africa South of the Sahara; Anus; Breast; Cancer Center; Cancer Patient; Caring; Cause of Death; Cellular Immunity; Clinic; Clinical; Clinical effectiveness; Collaborations; Complex; Country; Data; Development; Diagnosis; Disease; Documentation; Expert Opinion; Feedback; Future; General Population; Goals; Guidelines; HIV; HIV Infections; HIV diagnosis; HIV therapy; HIV/TB; Head and Neck Cancer; Health; Health system; High Prevalence; Hodgkin Disease; Hospitals; Human immunodeficiency virus test; Hybrids; Immune; Immune system; Immunosuppression; Immunotherapy; Institutes; Intervention; Interview; Kaposi Sarcoma; Liver; Lung; Maintenance; Malawi; Malignant Neoplasms; Malignant neoplasm of cervix uteri; Measures; Non-Hodgkin' s Lymphoma; Oncology; Outcome; Patients; Persons; Population; Pragmatic clinical trial; Prevalence; Process; Prostate; Questionnaires; Randomized; Records; Regional Cancer; Research; Resource-limited setting; Resources; Site; South Africa; Structure; System; Testing; Theoretical Domains framework; Treatment Side Effects; Treatment-Related Cancer; Uganda; Universities; Visit; Wit; Work; World Health Organization; Zimbabwe; antiretroviral therapy; base; cancer care; cancer diagnosis; cancer referral center; cancer survival; cancer therapy; care delivery; clinical care; design; effectiveness implementation study; effectiveness implementation trial; effectiveness trial; evidence base; evidence based guidelines; exhaustion; experience; experimental study; high risk; immune activation; immune function; implementation outcomes; implementation science; improved; infection risk; mortality; multidisciplinary; multimodality; neoplasm registry; success; therapy development; trial design; tuberculosis treatment; tumor

ABSTRACT In sub-Saharan Africa (SSA), the dual burdens of HIV and cancer pose challenges to health systems and exacerbate global inequities. People living with HIV (PLWH) are at higher risk of developing certain cancers, are less likely to receive cancer treatment, and experience higher cancer-specific mortality than persons without HIV. Antiretroviral therapy (ART) mitigates negative impact of HIV in certain cancers and may be critical to the success of cancer treatment among patients with cancer and HIV by decreasing immune exhaustion and restoring immune function. Despite this, there remains a lack of evidence-based recommendations for the integration of HIV treatment and cancer care, and for coordinating treatment initiation for ART-naïve people with cancer. Current guidelines for treating HIV in people with cancer are based on expert opinion, are not tailored for low- resource settings, and do not address the exact timing of ART initiation for patients who present with untreated HIV and different types and stages of cancer, and at different levels of immunosuppression. We call on the tremendous successes of a paradigm shift in integrated TB/HIV care that occurred following 3 large effectiveness trials of how and when to initiate ART in PLWH presenting for TB treatment. In Aim 1 of this proposal, we will measure the burden of treated and untreated HIV, and undiagnosed HIV among cancer patients, with focus on recent HIV diagnoses and proportion of patients who could benefit from initiation of ART during cancer treatment at regional cancer centers in Malawi, Zimbabwe, and South Africa. In Aim 2, we will evaluate systems-based barriers and facilitators to integration of cancer and HIV treatment using a theoretical domains framework and to identify ways to provide integrated care with cancer center staff and key stakeholders. In Aim 3, we will develop design strategy for a multi-country pragmatic clinical trial. We will perform process mapping to identify intervention points to coordinate HIV and cancer care and conduct discrete choice experiments with multidisciplinary staff to solicit feedback on design of a future randomized hybrid effectiveness-implementation trial of ART initiation strategies at regional cancer centers in Malawi, Zimbabwe, South Africa, and Uganda. We contend that ART as integral for HIV-associated cancer treatment is well generally supported, broadly available, and yet not uniformly a part of current cancer therapy in SSA. We are proposing the first multinational collaboration planned to address the HIV treatment component of HIV-associated cancer: this topic has not been fully addressed due to complex, siloed treatment systems and focus on the cancer component of care for people with cancer and HIV. Using the results of this planning work, we will propose the appropriate hybrid trial design to determine evidence-based ART initiation timing in a selected set of cancers, and to evaluate the impact of coordinated ART provision on both clinical outcomes including overall survival and adverse events, as well as implementation outcomes, such as initiation and persistence on ART, completion of intended cancer therapy, and HIV care transitions following completion of cancer therapy.

抽象的 在撒哈拉以南非洲（SSA）中，艾滋病毒和癌症的双重烧伤对卫生系统和 加剧全球不平等。患有艾滋病毒（PLWH）的人患某些癌症的风险更高，是 比没有艾滋病毒的患者接受癌症治疗的可能性较小，并且经历更高的癌症死亡率。 抗逆转录病毒疗法（ART）减轻艾滋病毒在某些癌症中的负面影响，可能对成功至关重要 通过减少免疫疲劳和恢复，癌症和HIV患者的癌症治疗 免疫功能。尽管如此，仍然缺乏基于证据的建议 HIV治疗和癌症护理，以及针对未经癌症患者的协调治疗计划。 癌症患者治疗艾滋病毒的当前指南是基于专家意见的，并不是针对低 - 资源设置，并且没有针对出现未经治疗的患者的艺术计划的确切时间安排 HIV，癌症的不同类型和阶段，以及不同水平的免疫抑制。我们呼吁 在3个巨大有效性之后发生的综合结核/艾滋病毒护理中范式转移的巨大成功 关于如何以及何时发起ART在PLWH呈现TB治疗的试验。在本提案的目标1中，我们将 测量癌症患者中治疗和未经治疗的HIV的伯宁和未经治疗的艾滋病毒，并关注 最近的HIV诊断和可能受益于癌症治疗中艺术启动的患者的比例 在马拉维，津巴布韦和南非的区域癌症中心。在AIM 2中，我们将评估基于系统的 使用理论领域框架和 确定与癌症中心工作人员和主要利益相关者提供综合护理的方法。在AIM 3中，我们将发展 多国务实临床试验的设计策略。我们将执行过程映射以识别 干预指向协调艾滋病毒和癌症护理，并与 多学科的工作人员征求有关未来随机混合有效性实施的设计的反馈 马拉维，津巴布韦，南非和乌干达地区癌症中心的艺术倡议策略试验。 我们认为，作为HIV相关癌症治疗不可或缺的ART得到了广泛支持，广泛支持 可用，但并不是SSA当前癌症治疗的一部分。我们提出了第一个跨国公司 计划解决与艾滋病毒相关癌症的艾滋病毒治疗部分：这个话题不是 由于复杂，孤立的治疗系统，完全解决了人们的护理癌症组成部分 癌症和艾滋病毒。使用此计划工作的结果，我们将提出适当的混合试验设计 确定选定的癌症中基于证据的艺术启动时间，并评估 在包括整体生存和不良事件在内的这两个临床结果上的协调艺术规定以及 实施结果，例如主动性和对艺术的持久性，预期癌症治疗的完成， 癌症治疗完成后的HIV护理过渡。