Deadline: July 13, 2012
Countries/Region: U.S
Host defense against viral infection necessitates a highly regulated balance between eliminating or reducing the invading pathogen and minimizing damage to the host. The inflammatory response is initiated when triggering stimuli are detected by sensors that translate signals through complex molecular and cellular networks to ultimately mediate the response to affected tissues and systems. Once the inducing stimulus is removed, the acute inflammatory response is normally terminated, inflammation resolved and damaged tissue repaired. During acute HIV infection, the immune system is highly activated as expected, however as infection proceeds to the chronic phase, the inflammatory response is not resolved. This leads to a state of chronic immune activation thought to be central to AIDS pathogenesis. Characteristics of this persistent immune activation include elevated T cell activation and turnover, polyclonal B cell activation and increased levels of pro-inflammatory cytokines and chemokines. Concomitant with activation, there is a progressive loss of CD4+ T cells and an impairment of effector T cell function often referred to as immune exhaustion. Studies in untreated humans and animal models show that the levels of chronic immune activation are strong predictors of disease progression in untreated HIV/SIV infection. While the inducing stimuli of chronic immune activation in untreated infection are likely multi-factorial, ongoing viral replication is likely a primary driver.
This FOA solicits applications that propose small proof-of-concept clinical trials, with concurrent intensive laboratory studies, designed to evaluate the effect of an intervention on chronic immune activation or persistent inflammation in HIV-infected individuals who are taking effective antiretroviral therapy. The intervention must have a known mechanism of action. The goal of this initiative is to identify specific mechanisms or pathways that can be targeted to prevent or reverse persistent immune activation in HIV-infected individuals.
Eligibligibility:
Higher Education Institutions
- Public/State Controlled Institutions of Higher Education
- Private Institutions of Higher Education
The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:
- Hispanic-serving Institutions
- Historically Black Colleges and Universities (HBCUs)
- Tribally Controlled Colleges and Universities (TCCUs)
- Alaska Native and Native Hawaiian Serving Institutions
Nonprofits Other Than Institutions of Higher Education
- Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Higher Education)
- Nonprofits without 501(c)(3) IRS Status (Other than Institutions of Higher Education)
For-Profit Organizations
- Small Businesses
- For-Profit Organizations (Other than Small Businesses)
Governments
- State Governments
- County Governments
- City or Township Governments
- Special District Governments
- Indian/Native American Tribal Governments (Federally Recognized)
- Indian/Native American Tribal Governments (Other than Federally Recognized)
- Eligible Agencies of the Federal Government
- U.S. Territory or Possession
- Other
- Independent School Districts
- Public Housing Authorities/Indian Housing Authorities
- Native American Tribal Organizations (other than Federally recognized tribal governments)
- Faith-based or Community-based Organizations
- Regional Organizations
Foreign Institutions
- Non-domestic (non-U.S.) Entities (Foreign Institutions) are not eligible to apply.
- Non-domestic (non-U.S.) components of U.S. Organizations are not eligible to apply.
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