Immune mediators associated with HPV clearance as predictors of HIV acquisition

与 HPV 清除相关的免疫介质可作为 HIV 感染的预测因子

• 批准号: 8992353
• 负责人: DAVID D. CELENTANO
• 金额: $ 18.65万
• 依托单位: CENTRE/AIDS PROGRAMME/RES/SOUTH AFRICA
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-02-01 至 2017-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8992353
• 关键词: AIDS prevention; Address; Affect; Africa South of the Sahara; Anogenital cancer; Anogenital venereal warts; Antibodies; Antibody Response; Biological; Biological Markers; Biological Response Modifiers; CCR5 gene; CD4 Positive T Lymphocytes; Cells; Cervical; Clinic; Cohort Studies; Data; Detection; Development; Enrollment; Environment; Epidemiology; Epithelial; Epithelium; Event; Family Planning; Future; Gel; Genital Human Papilloma Virus Infection; Genital system; HIV; HIV Infections; HIV risk; Health; Helper-Inducer T-Lymphocyte; High Prevalence; Human Papilloma Virus Vaccination; Human Papillomavirus; Human papilloma virus infection; Immune; Immune response; Immunology; Incidence; Individual; Infection; Inflammatory Response; Intervention; Link; Malignant neoplasm of cervix uteri; Measures; Mediating; Meta-Analysis; Metabolic Clearance Rate; Molecular; Mucosal Immune Responses; Natural History; Natural Killer Cells; Oncogenic; Participant; Pathway interactions; Personal Communication; Predisposition; Prevalence; Preventive Intervention; Production; Prospective Studies; Public Health; Research; Risk; Risk Factors; Role; Sexually Transmitted Diseases; Source; South Africa; T-Lymphocyte; Tenofovir; Testing; Time; Tissues; Vagina; Viremia; Virus; Virus Diseases; Woman; cellular targeting; cervicovaginal; cohort; design; hazard; improved; non-oncogenic; pathogen; prospective; response; seroconversion; sexual HIV transmission

 DESCRIPTION (provided by applicant): Genital human papillomavirus (HPV) is one of the most common sexually transmitted infections. In addition to its role as a necessary factor in the development of cervical and several anogenital cancers, a recent meta-analysis confirms that HPV is associated with up to 5-fold increased risk of HIV acquisition. Notably, this effect was even more pronounced among individuals who had recently cleared an HPV infection. Thus far no study has been systematically designed to determine potential mucosal mechanisms by which clearance of HPV may facilitate acquisition of HIV. We propose that molecular and immunological events associated with the detection and response to HPV infection, including mucosal production of HPV-specific antibodies, recruitment of activated T and NK cells, and disrupted epithelial integrity, may also serve as co-factors for subsequent HIV acquisition. We propose to test this hypothesis utilizing data from the ongoing CAPRISA 008 trial that tests the feasibility of integrating 1% tenofovir gel provision into family planning clinics. Specifically we will: 1) characterize the cellular and humoral immune responses, and level of genital epithelial integrity associated with HPV clearance; and 2) compare these mucosal correlates of HPV clearance in those who acquire HIV compared to those who do not acquire HIV. HPV infection does not cause viremia; and seroconversion only occurs in about 60% of individuals, and even then only late in natural infection. Despite these observations underscoring the importance of understanding local responses to genital HPV infection the mucosal immunology of HPV infection is still poorly understood. This prospective study provides an ideal opportunity to bette understand the biological underpinnings of the strong epidemiological association between the clearance of HPV infection and enhanced HIV acquisition. The high prevalence of HPV infection in sub- Saharan Africa, together with high HPV clearance rates within 8-12 months, will enhance our understanding of its relative contribution to HIV acquisition and inform the design of appropriate interventions to reduce HIV acquisition rates. A better understanding of the associations between clearance of genital HPV infection and HIV acquisition is critical to addressing larger research questions that include (1) how to limit a deleterious effect of common HPV infections on HIV and (2) whether HPV vaccination has the potential to impact HIV incidence, taking into consideration complexities such as mucosal immune responses over time, number and type of HPV infections, and other risk factors. By enhancing understanding of the biological mechanism that underpins the compelling and consistent epidemiological evidence we can begin to identify and inform appropriate, targeted and specific HIV prevention interventions.