HIV/cervical cancer cOntrol and Prevention clinical sitE in Kenya (HOPE-Kenya) - Modified Project Summary/Abstract Section Cervical cancer (CC) is a highly preventable disease, yet hundreds of thousands of women die each year from CC, with the large majority of deaths occurring in low- and middle-income countries (LMICs). CC places a substantial burden on populations with elevated CC burden in the United States (U.S.), particularly those living with HIV, making global research on prevention and treatment directly relevant to domestic public health. LMICs in sub-Saharan Africa (SSA) are particularly affected because of the dual burden of human papillomavirus (HPV) and HIV infection, which interact with deadly synergism. Women living with HIV (WLWH) have accessed antiretroviral therapy (ART) across SSA but have yet to fully benefit from integrated CC screening and treatment services. The challenges lie not in any particular barrier to care but in the many gaps that occur in the cascade of CC prevention — from screening uptake to management of positive cases to treatment access and application. These same cascade gaps persist among WLWH in the U.S., and evidence-based interventions developed in high-burden settings are directly translatable to U.S. clinical practice and screening guidelines. Clinical research sites are needed worldwide to implement clinical trials that examine potential interventions, and one of the most ideal locations may be found at the Coptic Hope Center for Infectious Diseases in Nairobi, Kenya. Co-founded by Dr. Michael Chung (MPI) and Dr. Samah Sakr (MPI) at the Coptic Hospital in 2004, the Hope Center is one of the largest single-site ART treatment centers in Kenya, having enrolled over 20,000 people living with HIV (PLWH), with over 6,000 WLWH currently in care. The Hope Center has been screening WLWH for cervical cancer since 2005 and has served as the site for HIV-CC research and numerous clinical trials conducted by Treatment, Research, and Expert Education (TREE), which Dr. Chung leads as Executive Director. Based at the Hope Center, TREE has a powerful physical, administrative, and laboratory infrastructure that has been implementing HIV clinical trials at the site for over a decade, including a study that screened over 6,000 WLWH with Papanicolaou (Pap) smear and colposcopy-directed biopsy, randomized 400 participants to cryotherapy and loop electrosurgical excision procedure (LEEP), and examined recurrence of cervical intraepithelial neoplasia (CIN), cervical shedding of HIV, and clearance of HPV over 2-year follow-up. The biological insights generated — including HPV clearance dynamics, CIN recurrence rates, and the interplay between ART and CC outcomes — have direct applicability to U.S. clinical guidelines and the care of WLWH domestically. In this proposal, Dr. Chung and Dr. Sakr will co-lead the implementation of a clinical site at the Hope Center in Nairobi by Coptic Hospital and TREE that, with assistance from Drs. Mary Nderitu (co-I) and Evans Nyongesa-Malav (co-I), will study interventions that will: 1) increase screening uptake among WLWH; 2) improve management of women who screen positive; and 3) optimize precancer treatment for WLWH. They will achieve this by providing: 1) a pluripotent infrastructure for accruing participants to network clinical trials from the Hope Center and a network of four Coptic HIV Clinics throughout the country, overseen by Dr. Mark Mounir (co-I), for a total of 6,533 CC screen-eligible WLWH between the ages of 25 and 49; 2) insights and input on clinical significance and study feasibility during concept and protocol development through the participation of Dr. Chung and Dr. Sakr; and 3) on-site operational leadership for the successful conduct of network clinical trials by TREE and its staff, led by Dr. Rose Kosgei (co-I). The trial methods, implementation frameworks, and operational infrastructure developed through this work will strengthen U.S. researchers' capacity to lead rigorous international collaborative science and inform domesti
