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

基本信息

项目摘要

 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.


项目成果

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DAVID D. CELENTANO其他文献

DAVID D. CELENTANO的其他文献

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{{ truncateString('DAVID D. CELENTANO', 18)}}的其他基金

Identifying and Engaging Urban HIV infected and uninfected YSMSM in care
识别城市艾滋病毒感染者和未感染者 YSMSM 并让他们参与护理
  • 批准号:
    10214911
  • 财政年份:
    2016
  • 资助金额:
    $ 14.71万
  • 项目类别:
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
  • 财政年份:
    2015
  • 资助金额:
    $ 14.71万
  • 项目类别:
Prevention Core
预防核心
  • 批准号:
    10153641
  • 财政年份:
    2012
  • 资助金额:
    $ 14.71万
  • 项目类别:
Prevention
预防
  • 批准号:
    8292628
  • 财政年份:
    2012
  • 资助金额:
    $ 14.71万
  • 项目类别:
Prevention Core
预防核心
  • 批准号:
    10612982
  • 财政年份:
    2012
  • 资助金额:
    $ 14.71万
  • 项目类别:
Prevention Core
预防核心
  • 批准号:
    10458361
  • 财政年份:
    2012
  • 资助金额:
    $ 14.71万
  • 项目类别:
Using Technology to Prevent HIV in Indian Wine Shops
在印度葡萄酒商店中利用技术预防艾滋病毒
  • 批准号:
    8139287
  • 财政年份:
    2010
  • 资助金额:
    $ 14.71万
  • 项目类别:
Preventing HIV Infection Among MSM in Southern India
印度南部男男性接触者中预防艾滋病毒感染
  • 批准号:
    7928429
  • 财政年份:
    2010
  • 资助金额:
    $ 14.71万
  • 项目类别:
Preventing HIV Infection Among MSM in Southern India
印度南部男男性接触者中预防艾滋病毒感染
  • 批准号:
    8918742
  • 财政年份:
    2010
  • 资助金额:
    $ 14.71万
  • 项目类别:
Preventing HIV Infection Among MSM in Southern India
印度南部男男性接触者中预防艾滋病毒感染
  • 批准号:
    8135030
  • 财政年份:
    2010
  • 资助金额:
    $ 14.71万
  • 项目类别:

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