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: 10252626
• 负责人: Rachel Ann Bender Ignacio
• 金额: $ 16.24万
• 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 2023-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10252626
• 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; 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)，艾滋病毒和癌症的双重负担给卫生系统和医疗机构带来了挑战。 全球不平等现象日益恶化，艾滋病毒感染者 (PLWH) 患某些癌症的风险更高。 与未感染艾滋病毒的人相比，接受癌症治疗的可能性较小，并且癌症特异性死亡率较高。 抗逆转录病毒疗法（ART）可减轻艾滋病毒对某些癌症的负面影响，并且可能是成功的关键 通过减少免疫衰竭和恢复免疫功能来治疗癌症和艾滋病毒患者 尽管如此，仍然缺乏基于证据的整合建议。 HIV 治疗和癌症护理，以及协调未接受过 ART 的癌症患者的治疗启动。 目前治疗癌症患者艾滋病毒的指南是基于专家意见，并非针对低收入人群。 资源设置，并且没有解决未经治疗的患者开始 ART 的确切时间 HIV 与不同类型和阶段的癌症以及不同水平的免疫抑制。 结核病/艾滋病毒综合护理范式转变取得了巨大成功，取得了 3 大成效 关于如何以及何时在接受结核病治疗的感染者中启动 ART 的试验 在本提案的目标 1 中，我们将进行试验。 衡量癌症患者中已治疗和未治疗的艾滋病毒以及未诊断的艾滋病毒的负担，重点是 最近的艾滋病毒诊断以及在癌症治疗期间可以从开始抗逆转录病毒治疗中受益的患者比例 在马拉维、津巴布韦和南非的区域癌症中心，我们将评估基于系统的情况。 使用理论领域框架来确定癌症和艾滋病毒治疗整合的障碍和促进因素，并 在目标 3 中，我们将制定与癌症中心工作人员和主要利益相关者一起提供综合护理的方法。 我们将进行流程图以确定多国实用临床试验的设计策略。 协调艾滋病毒和癌症护理的干预点，并进行离散选择实验 多学科工作人员就未来随机混合有效性实施的设计征求反馈 在马拉维、津巴布韦、南非和乌干达的区域癌症中心试验 ART 启动策略。 我们认为，ART 作为 HIV 相关癌症治疗不可或缺的一部分得到了广泛支持 可用，但尚未成为 SSA 当前癌症治疗的一部分。我们提议采用第一个跨国疗法。 计划合作解决艾滋病毒相关癌症的艾滋病毒治疗部分：该主题尚未得到解决 由于复杂、孤立的治疗系统和对人们护理中癌症部分的关注而得到充分解决 利用这项规划工作的结果，我们将提出适当的混合试验设计。 确定针对一组选定癌症的基于证据的 ART 启动时机，并评估其影响 协调 ART 提供的临床结果，包括总体生存率和不良事件，以及 实施结果，例如 ART 的启动和持续、癌症治疗的完成、 癌症治疗完成后艾滋病毒护理的转变。