Implementing HIV/Cervical Cancer Prevention CASCADE Clinical Trials in Uganda (CASCADE UGANDA)

PROJECT SUMMARY/ABSTRACT Uganda is one of 8 countries with the highest burden of cervical cancer (CXCA) among women living with HIV (WLWH) with an HIV-attributable age-standardized incidence rate of 10–20 per 100,000. Strategies for Cervical Cancer (CXCA) prevention include targeted Human Papillomavirus (HPV) vaccination, screening of women aged

25-49-years by visual inspection with acetic acid (VIA) or HPV DNA testing, and precancer treatment by cryotherapy or ablation. However, there is limited and sparse availability of and access to CXCA interventions which is compounded by low-uptake of ‘screen and treat’ strategies. Scalable, affordable, point-of-care, clinically

proven novel interventions (including HPV self-sampling techniques, HPV molecular biomarker tests, precancer diagnostics and imaging techniques, and ablative and excisional treatments) are imperative. Further, the effectiveness of these novel clinically proven interventions remains unknown which limits implementation in

intended-use settings in the US and low- and middle-income countries (LMICs). To support on-going efforts to roll-out novel screen and treat strategies, the Makerere University Walter Reed Project (MUWRP) in partnership with the U.S. Military HIV Research Program (MHRP) propose to participate in the HIV/Cervical Cancer

Prevention ‘CASCADE’ Clinical Trials Network as a UG1 Clinical Research Site (UG1 CRS) to implement pragmatic clinical trials in Uganda. We will: 1) leverage MUWRP’s expertise and experience in clinical trials and CXCA prevention among WLWH to provide valuable insight and input on study feasibility, clinical significance

and local context during concept and protocol development; 2) accrue CASCADE targets in a timely manner and retain ≥ 95% of study participants leveraging MUWRP’s pluripotent experience, clinical research infrastructure and resources; and 3) provide competent leadership to ensure procedural fidelity to protocols and all applicable

regulations and guidelines. MUWRP will also support UG1 Research Bases and U24 Coordination Center to obtain ethical and regulatory approvals for CASCADE trials, and implement clinical trial protocols with fidelity. MUWRP is an ideal and rational choice for a UG1 CRS as MUWRP has: 1) access to over 37,000 WLWH in

urban, semi-urban, and rural settings at 114 health facilities supported by MUWRP’s Comprehensive HIV/AIDS Prevention, Care and Treatment in Central Uganda (CARE) program funded by the U.S. President's Emergency Plan for AIDS Relief (PEPFAR); 2) extensive experience conducting HIV clinical research and CXCA screening

and precancer treatment in the African Cohort Study, and CARE supported CXCA program; and 3) internationally renowned scientists with experience and expertise in conducting clinical trials involving WLWH in Uganda and other LMICs. MUWRP’s expertise and capacity will support all four research focus areas of the CASCADE

Network. MUWRP and MHRP will generate evidence that ultimately informs CXCA policy and screen and treat strategies for WLWH.