Human Papillomavirus Infection in Perinatally HIV-infected Adolescents in Asia

亚洲围产期艾滋病毒感染青少年的人乳头瘤病毒感染

• 批准号: 8522212
• 负责人: NITTAYA PHANUPHAK
• 金额: $ 60.51万
• 依托单位: FOUNDATION FOR AIDS RESEARCH
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-08-03 至 2017-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8522212
• 关键词: 12 year old; 16 year old; Address; Adolescence; Adolescent; Adult; Age; Age-Years; Anogenital Human Papilloma Virus Infection; Antibodies; Antibody Formation; Anus; Asia; Asians; Behavioral; Biological; Biopsy; Case-Control Studies; Cervical; Cervical Intraepithelial Neoplasia; Cervix Uteri; Child; Childhood; Clinical; Collaborations; Colposcopy; Contraceptive methods; Control Groups; Country; Cytology; Data; Disease; Eligibility Determination; Female; Female Adolescents; Genotype; HIV; HIV Infections; HIV Seropositivity; HPV-High Risk; High Prevalence; Human Papilloma Virus Vaccine; Human Papillomavirus; Human papilloma virus infection; Human papillomavirus 16; Human papillomavirus 18; Incidence; Infection; Infection prevention; Intervention; Intraepithelial Neoplasia; Knowledge; Lead; Level of Evidence; Life; Male Adolescents; Male Genital Organs; Malignant Neoplasms; Messenger RNA; Monitor; Natural History; Oncogene Proteins; Oncogenes; Oncogenic; Oral; Oral cavity; Pattern; Pilot Projects; Population; Prevalence; Reporting; Research; Research Personnel; Risk; Risk Behaviors; Risk Factors; Sampling; Serum; Sex Behavior; Sexual Partners; Sexually Transmitted Diseases; Smoking; Southeastern Asia; Squamous intraepithelial lesion; Staging; Testing; Thailand; Time; Vaccination; Vaccines; Vagina; Vietnam; Virus; Visit; antiretroviral therapy; boys; cervical and anal cancer; clinical research site; cohort; experience; follow-up; high risk; male; neutralizing antibody; pediatric human immunodeficiency virus; prevent; public health relevance; scale up; sexual debut; sexually active; vaccination strategy

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.

描述（由申请人提供）：由东南亚6个国家的16个儿科HIV临床中心组成的amfAR TREAT Asia Pediatric Network的数据显示，在积极随访的2810名HIV儿童的区域观察队列中，41%的年龄超过12岁。这些儿童现在正经历着长期接触抗逆转录病毒疗法和艾滋病毒疾病的影响，同时进入青春期并开始性活跃。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瘤病毒（HPV），初次性行为的中位年龄为15岁，目前的中位年龄为16岁。很少有人知道口腔或肛门生殖器HPV感染的HIV感染的亚洲男性青少年。本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HIV感染和未感染青少年HPV感染的早期自然史以及HPV获得和持续存在的风险因素。研究目标将通过纵向病例对照研究来实现，该研究在泰国的三个参与临床研究中心和越南的一个临床研究中心进行，在12-24岁的围产期HIV感染和匹配的HIV未感染青少年女性和男性中进行，为期144周。青少年将性活跃，并充分披露他们是否感染艾滋病毒。年度研究访视将在第0、48、96和144周进行;女性将进行额外的年中HPV检测访视。通过对来自多个身体隔室的样本进行基因分型，并检测HPV 16和HPV 18特异性中和抗体、E6/E7 mRNA和E6癌蛋白，评估女性和男性的HPV感染。将通过检查感染和疫苗基因型的可用抗体滴度（即，6、11、16、18）。评估性行为和其他潜在的行为和生物风险行为将确定降低早期HPV感染风险的可能机会。研究者将通过细胞学检测和阴道镜检查前瞻性监测宫颈鳞状上皮内病变和上皮内瘤变。 宫颈活检在初次性行为后不久检测宫颈、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，将有助于更深入地了解终身HIV感染背景下的HPV合并感染，并为HPV疫苗接种提供策略。这项研究将产生第一个区域水平的证据，以指导亚洲围产期HIV感染青少年的HPV感染预防和宫颈上皮内瘤变监测。