Human Papillomavirus Infection in Perinatally HIV-infected Adolescents in Asia

描述(由申请人提供)：由东南亚六个国家的16个儿科艾滋病毒临床中心组成的AMFAR亚洲治疗儿科网络的数据显示，在积极跟进的2810名艾滋病毒携带者的区域观察队列中，41%的人年龄在12岁以上。这些儿童现在正在经历长期接触抗逆转录病毒药物和艾滋病毒疾病的影响，同时进入青春期和性行为活跃。来自泰国曼谷的试点数据显示，50%的性活跃、围产期感染艾滋病毒的青少年女性已经感染了人乳头状瘤病毒(HPV)，首次性行为的中位年龄为15岁，目前的中位年龄为16岁。对感染艾滋病毒的亚洲男性青少年中口腔或肛门感染HPV的情况知之甚少。这项研究将通过监测宫颈、阴道、肛门(女性和男性)、口腔(女性和男性)、阴茎和阴囊HPV感染以及宫颈上皮内瘤变，评估亚洲艾滋病毒感染和未感染青少年中HPV感染的早期自然病史和HPV感染和持续存在的危险因素。研究目标将通过在泰国的三个参与临床地点和越南的一个临床地点进行144周以上的纵向病例对照研究，在12-24岁的围产期感染艾滋病毒和匹配的未感染艾滋病毒的青少年女性和男性中进行。青少年将保持性行为活跃，并充分披露他们是否感染了艾滋病毒。每年的研究访问将在0、48、96和144周进行；女性将在年中进行额外的HPV检测访问。将通过对来自多个身体间隔的样本进行基因分型，以及检测HPV16和HPV18特异性中和抗体、E6/E7mRNA和E6癌蛋白来评估女性和男性的HPV感染。将通过检查感染和可获得的疫苗基因型抗体效价(即6、11、16、18)来探索疫苗资格。对性行为和其他潜在的行为和生物危险行为的评估将确定可能的机会，以降低早期HPV感染的风险。调查人员将通过细胞学检查和阴道镜检查来前瞻性地监测宫颈鳞状上皮内病变和上皮内瘤变 宫颈活检。在性交后不久检测宫颈、阴道、肛门、口腔和男性生殖器中的HPV感染，并随着时间的推移监测病毒清除和宫颈上皮内瘤变，将有助于加深对终身HIV感染背景下HPV合并感染的理解，并为HPV疫苗接种策略提供参考。这项研究将产生第一个地区性证据来指导亚洲围产期感染艾滋病毒的青少年的HPV感染预防和宫颈上皮内瘤变监测。

DESCRIPTION (provided by applicant): Data from amfAR's TREAT Asia Pediatric Network, composed of 16 pediatric HIV clinical centers in six countries in Southeast Asia show that 41% of their regional observational cohort of 2810 children with HIV in active follow-up is over the age of 12 years. These children are now experiencing the impact of long-term ART exposure and HIV disease, while at the same time entering into adolescence and becoming sexually active. Pilot data from Bangkok, Thailand have shown that 50% of sexually active, perinatally HIV-infected adolescent females were already infected with human papillomavirus (HPV), at a median age at sexual debut of 15 years and a current median age of 16 years. Little is known about oral or anogenital HPV infection in HIV-infected Asian male adolescents. This study will evaluate the early natural history of HPV infection and risk factors for HPV acquisition and persistence among HIV-infected and -uninfected adolescents in Asia by monitoring for cervical, vaginal, anal (female and male), oral (female and male), penile, and scrotal HPV infection, and cervical intraepithelial neoplasia. The research aims will be accomplished through longitudinal case-control studies within a cohort of perinatally HIV-infected and matched HIV-uninfected adolescent females and males between 12-24 years of age, over 144 weeks in three participating clinical sites in Thailand and one in Vietnam. Adolescents will be sexually active and fully disclosed to if they have HIV. Annual study visits will take place at weeks 0, 48, 96, and 144; females will have additional mid-year HPV testing visits. HPV infection will be assessed in both females and males by genotyping samples from multiple body compartments, and testing for HPV 16- and HPV 18-specific neutralizing antibody, E6/E7 mRNA, and E6 oncoprotein. Vaccine eligibility will be explored by examining infection with and available antibody titers to vaccine genotypes (i.e., 6, 11, 16, 18). Assessments of sexual and other potential behavioral and biological risk behaviors will identify possible opportunities to reduce the risk of early HPV infection. Investigators will prospectively monitor for cervical squamous intraepithelial lesions and intraepithelial neoplasia with cytology testing and colposcopy-directed cervical biopsy. Detecting HPV infection in the cervix, vagina, anus, oral cavity, and male genitalia soon after sexual debut and monitoring virus clearance and cervical intraepithelial neoplasia over time will lead to a deeper understanding of HPV co-infection in the context of life-long HIV infection, and inform strategies for HPV vaccination. This study will produce the first regional-level evidence to guide HPV infection prevention and cervical intraepithelial neoplasia monitoring for perinatally HIV-infected adolescents in Asia.