HIV/cervical cancer cOntrol and Prevention clinical sitE in Kenya (HOPE-Kenya)

摘要 宫颈癌是一种高度可预防的疾病，但每年仍有数十万妇女死亡 大多数死亡发生在低收入和中等收入国家。位于亚洲区的LMIC 由于人类乳头瘤病毒(HPV)和人类乳头瘤病毒(HPV)的双重负担，撒哈拉非洲地区受到的影响尤其严重 艾滋病毒感染与致命的协同作用相互作用。艾滋病毒携带者(WLWH)妇女已获得抗逆转录病毒药物 治疗(ART)横跨SSA，但尚未完全受益于整合的CC筛查和治疗服务。 挑战不在于任何特定的关爱障碍，而在于CC级联中出现的许多缺口 预防从筛查、吸收到管理阳性病例，再到获得和应用治疗。临床 世界各地需要研究地点来实施临床试验，以检查潜在的干预措施和 最理想的地点可能是肯尼亚内罗毕的科普特希望传染病中心。共同-- 由Michael Chung博士(MPI)和Samah Sakr博士(MPI)于2004年在科普特医院创立的希望中心 是肯尼亚最大的单点抗逆转录病毒治疗中心之一，已招募了20,000多名与 艾滋病毒(PLWH)，目前有6,000多名WLWH在接受治疗。霍普中心一直在对WLWH进行宫颈筛查 癌症自2005年以来一直是艾滋病毒CC研究和许多临床试验的治疗场所， 研究和专家教育(TREE)，钟博士作为执行董事领导。立足于希望 TREE拥有强大的物理、管理和实验室基础架构，该基础架构一直在实施 在该地点进行了十多年的艾滋病毒临床试验，包括一项研究，该研究筛查了6000多名WLWH 巴氏涂片和阴道镜引导的活检，随机选择400人进行冷冻和循环治疗 电切术(LEEP)，并检查宫颈上皮内瘤变(CIN)的复发， 宫颈脱出HIV，HPV清除超过2年随访。在这项提案中，钟博士和萨克尔博士 将由科普特医院和TREE共同领导在内罗毕希望中心的一个临床地点的实施， 在Mary Nderitu博士(co-I)和Evans Nyongesa-Malav(co-I)的帮助下，将研究 将：1)增加WLWH的筛查接受率；2)改善对筛查阳性的妇女的管理；以及 3)优化WLWH的癌前治疗。他们将通过以下方式实现这一目标：1)提供多功能基础设施 从希望中心和由四个科普特艾滋病毒诊所组成的网络召集参与者进行临床试验 在全国范围内，由Andrew Nagy博士(co-I)监督，总共有6,533名CC筛查符合条件 25岁至49岁的WLWH；2)对临床意义和研究可行性的见解和投入 通过钟博士和萨克尔博士的参与制定概念和方案；以及3)和现场 TREE及其以Rose博士为首的员工成功进行网络临床试验的运营领导 Kosgei(co-i)。

ABSTRACT Cervical cancer (CC) is a highly preventable disease and 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). 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. 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 been the site for HIV CC research and many 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 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. 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 that are overseen by Dr. Andrew Nagy (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) and on-site operational leadership for the successful conduct of network clinical trials by TREE and its staff led by Dr. Rose Kosgei (co-I).