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.

 描述（由适用提供）：生殖器人乳头瘤病毒（HPV）是最常见的性传播感染之一。除了作为宫颈和几种肛门生殖器癌的发展的必要因素外，最近的一项荟萃​​分析证实，HPV与艾滋病毒获取风险的增加高达5倍。值得注意的是，在最近清除HPV感染的个体中，这种影响更加明显。该研究尚未系统地设计为确定HPV清除可能有助于获得HIV的潜在粘膜机制。我们提出，与HPV感染的检测和反应相关的分子和免疫学事件，包括粘膜的产生HPV特异性抗体，激活的T和NK细胞的募集以及上皮完整性的破坏，也可以用作随后的HIV获得的co因素。我们建议利用正在进行的CAPRISA 008试验中的数据来检验这一假设，该试验测试了将1％Tenofovir Gel提供到计划生育诊所的可行性。特别是我们 意志：1）表征细胞和体液免疫反应，以及与HPV清除相关的生殖器上皮完整性的水平； 2）比较那些获得HIV的人与未获得HIV的人相比，将HPV清除的这些粘膜相关性比较。 HPV感染不会引起病毒血症；血清转化仅发生在约60％的个体中，即使在自然感染中也很晚。尽管这些观察结果是理解当地对生殖器HPV感染的局部反应的重要性，但HPV感染的粘膜免疫学仍然知之甚少。这项前瞻性研究提供了一个理想的机会，可以更好地了解HPV感染和增强HIV的清除率之间强烈的流行病学关联的生物学基础。在8-12个月内，撒哈拉以南非洲的HPV感染率很高，以及HPV清除率高，将增强我们对其对HIV获取的相对贡献的理解，并为降低HIV习得率的适当干预措施提供了启用。更好地理解生殖器HPV感染和HIV的清除之间的关联对于解决更大的研究问题至关重要，包括（1）如何限制常见的HPV感染对HIV的有害影响以及（2）HPV疫苗接种可能会影响HIV的潜力，是否有可能影响Mucosal Implectiation的复杂性，例如Imcune Immune Amplection Amperne Immune Amplection Amperne Immune Resprience Experne Affection and higne prive higne and higne and typers and类型和其他类型的hpv and类型和其他数量sopers and类型。通过增强对基于引人注目且一致的流行病学证据的生物学机制的理解，我们可以开始识别和告知适当，有针对性和特定的HIV预防干预措施。