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 大部分死亡发生在低收入和中等收入国家（LMIC）。中低收入国家 撒哈拉非洲（SSA）由于人乳头瘤病毒（HPV）的双重负担而受到特别影响， 艾滋病毒感染与致命协同作用相互作用。感染艾滋病毒的妇女（WLWH）获得抗逆转录病毒治疗 在整个撒哈拉以南非洲地区，艾滋病毒/艾滋病治疗（ART）已经取得了进展，但尚未从综合CC筛查和治疗服务中充分受益。 挑战不在于任何特定的护理障碍，而在于CC级联中出现的许多差距。 从筛查到阳性病例的管理，再到治疗的获得和应用。临床 需要在全球范围内建立研究中心，以实施临床试验，检查潜在的干预措施， 最理想的地点可以在肯尼亚内罗毕的科普特希望传染病中心找到。共- 由Michael Chung博士（MPI）和Samah Sakr博士（MPI）于2004年在科普特医院创立，希望中心 是肯尼亚最大的单点ART治疗中心之一，已招募了20，000多名患有 艾滋病毒感染者（艾滋病毒携带者和艾滋病病毒携带者），目前有6 000多名艾滋病毒携带者和艾滋病病毒携带者在接受治疗。希望中心一直在筛查WLWH的宫颈癌 自2005年以来一直是艾滋病毒CC研究和治疗进行的许多临床试验的网站， 研究和专家教育（TREE），钟博士担任执行董事。基于希望 中心，树有一个强大的物理，行政和实验室基础设施，一直在实施 在该中心进行了十多年的艾滋病毒临床试验，包括一项筛选了6,000多名WLWH的研究， 巴氏（Pap）涂片和阴道镜导向活检，400例随机接受冷冻治疗和环扎 电外科切除术（LEEP），并检查宫颈上皮内瘤样病变（CIN）的复发， 宫颈脱落HIV，HPV清除超过2年随访。在这份提案中，钟博士和萨克博士 将共同领导科普特医院和TREE在内罗毕希望中心的临床站点的实施， 在玛丽·恩德里图博士（共同主席）和埃文斯·尼永格萨-马拉夫博士（共同主席）的协助下，将研究干预措施， 将：1）增加WLWH中的筛查率; 2）改善对筛查阳性妇女的管理;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）多能基础设施， 从希望中心和一个由四个科普特艾滋病毒诊所组成的网络中招募参与者参加网络临床试验， 由Andrew Nagy博士（co-I）监督的全国各地共有6，533名符合CC筛选条件的患者 WLWH年龄在25岁至49岁之间; 2）在研究期间对临床意义和研究可行性的见解和意见 通过Chung博士和Sakr博士的参与制定概念和方案;以及3）和现场 由Rose博士领导的TREE及其工作人员成功开展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).