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

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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.