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(SSA)，艾滋病毒和癌症的双重负担对卫生系统和 加剧全球不平等。艾滋病毒携带者(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更小，癌症特有的死亡率更高。 抗逆转录病毒疗法(ART)减轻艾滋病毒对某些癌症的负面影响，这可能是成功的关键 减少免疫衰竭和恢复对癌症和HIV患者的癌症治疗 免疫功能。尽管如此，仍然缺乏以证据为基础的建议，以整合 艾滋病毒治疗和癌症护理，以及协调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的意见，而不是为低收入人群量身定做的 资源设置，并且没有解决未经治疗的患者开始抗逆转录病毒治疗的确切时间 HIV与不同类型和不同阶段的癌症，以及处于不同水平的免疫抑制有关。我们呼吁 在三大成效之后，结核病/艾滋病毒综合护理的范式转变取得了巨大成功 如何以及何时在PLWH中启动抗逆转录病毒治疗的试验。在本提案的目标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诊断的艾滋病毒的负担，重点是 最近的艾滋病毒诊断和癌症治疗期间可以从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。在目标2中，我们将评估基于系统的 使用理论领域框架整合癌症和艾滋病毒治疗的障碍和促进者 确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。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以确定 干预点，协调艾滋病毒和癌症护理，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的设计征求反馈-实施 在马拉维、津巴布韦、南非和乌干达的区域癌症中心试验抗逆转录病毒治疗启动策略。 我们认为，抗逆转录病毒疗法作为艾滋病毒相关癌症治疗中不可或缺的一部分，得到了广泛的支持。 可用，但不是SSA当前癌症治疗的一部分。我们提出了第一家跨国企业 计划开展合作，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 由于复杂、孤立的治疗系统而得到充分解决，并将重点放在人们护理的癌症部分上 癌症和艾滋病患者。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 在选定的一组癌症中确定循证的ART启动时间，并评估 协调提供关于临床结果的抗逆转录病毒药物治疗，包括总体生存和不良事件，以及 实施结果，如启动和坚持抗逆转录病毒治疗，完成预期的癌症治疗， 以及癌症治疗完成后艾滋病毒护理的过渡。

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.