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

摘要 在撒哈拉以南非洲，艾滋病毒和癌症的双重负担对卫生系统构成挑战， 加剧全球不平等。艾滋病毒感染者（PLWH）患某些癌症的风险更高， 艾滋病毒感染者接受癌症治疗的可能性更小，癌症死亡率高于未感染艾滋病毒的人。 抗逆转录病毒疗法（ART）减轻了艾滋病毒对某些癌症的负面影响，可能是成功的关键 通过减少免疫衰竭和恢复免疫功能， 免疫功能尽管如此，仍然缺乏关于将 艾滋病毒治疗和癌症护理，以及协调对未经抗逆转录病毒治疗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，不是针对低- 资源设置，并没有解决的确切时间ART启动的患者谁目前未经治疗 艾滋病毒与不同类型和阶段的癌症，以及不同水平的免疫抑制。我们呼吁 结核病/艾滋病综合治疗模式转变的巨大成功， 试验如何以及何时开始抗逆转录病毒疗法在PLWH提出结核病治疗。在本建议的目标1中，我们将 衡量癌症患者中已治疗和未治疗的艾滋病毒以及未确诊的艾滋病毒的负担，重点是 最近的艾滋病毒诊断和在癌症治疗期间可以从开始抗逆转录病毒治疗中获益的患者比例 在马拉维、津巴布韦和南非的地区癌症中心。在目标2中，我们将评估基于 使用理论领域框架整合癌症和HIV治疗的障碍和促进因素， 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。在目标3中，我们将开发 多国实用临床试验的设计策略。我们将执行流程映射， 协调艾滋病毒和癌症护理的干预点，并进行离散选择实验， 多学科工作人员征求对未来随机混合有效性实施设计的反馈 在马拉维、津巴布韦、南非和乌干达的区域癌症中心进行ART启动策略的试验。 我们认为，ART作为HIV相关癌症治疗的一个组成部分得到了广泛的支持， 但是，这并不是SSA目前癌症治疗的一部分。我们建议第一个跨国公司 计划合作解决艾滋病毒相关癌症的艾滋病毒治疗部分：这一主题尚未得到 由于复杂的孤立的治疗系统， 癌症和艾滋病利用这一规划工作的结果，我们将提出适当的混合试验设计 在选定的一组癌症中确定基于证据的ART启动时间，并评估 协调ART提供临床结局，包括总生存期和不良事件，以及 实施结果，如ART的开始和持续，预期癌症治疗的完成， 以及完成癌症治疗后的艾滋病毒护理过渡。

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.