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HIV VACCINE ELECTRONIC (E) RESOURCE
ID#: PA-12-107     Posted: 21 Feb 2012
Delivering Therapeutics to Residual Active HIV Reservoirs (R01)
Deadline: 5 Feb 2013
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Type of Grant: Research
Topics/Fields of Support: T cell immunity
National Institutes of Health (NIH, NIAID, NIMH)

The National Institutes of Health (NIH), a part of the U.S. Department of Health and Human Services, is the nation’s medical research agency—making important medical discoveries that improve health and save lives.

Thanks in large part to NIH-funded medical research, Americans today are living longer and healthier. Life expectancy in the United States has jumped from 47 years in 1900 to 77 years today, and disability in people over age 65 has dropped dramatically in the past 3 decades. In recent years, nationwide rates of new diagnoses and deaths from all cancers combined have fallen significantly.

Scientific Leadership

NIH is the largest source of funding for medical research in the world, creating hundreds of thousands of high-quality jobs by funding thousands of scientists in universities and research institutions in every state across America and around the globe.

NIH is made up of 27 Institutes and Centers, each with a specific research agenda, often focusing on particular diseases or body systems. NIH leadership plays an active role in shaping the agency's activities and outlook.

The Office of the Director is the central office at NIH, responsible for setting policy for NIH and for planning, managing, and coordinating the programs and activities of all the NIH components. The NIH Director, with a unique and critical perspective on the entire agency, is responsible for providing leadership to the Institutes and for constantly identifying needs and opportunities, especially for efforts that involve multiple Institutes. The NIH Director is assisted by the NIH Deputy Directors including the Principal Deputy Director, who shares in the overall direction of the agency's activities.

More than 80% of the NIH's budget goes to more than 300,000 research personnel at over 3,000 universities and research institutions. In addition, about 6,000 scientists work in NIH’s own laboratories, most of which are on the NIH main campus in Bethesda, Maryland. The main campus is also home to the NIH Clinical Center, the largest hospital in the world totally dedicated to clinical research.

Successful biomedical research depends on the talent and dedication of the scientific workforce. NIH supports many innovative training programs and funding mechanisms  that foster scientific creativity and exploration. The goal is to strengthen our nation’s research capacity, broaden our research base, and inspire a passion for science in current and future generations of researchers.


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DETAILS

Purpose

The purpose of this FOA is to encourage new ideas for eliminating residual reservoirs of HIV that persist in individuals despite long-term suppression of plasma viremia by traditional antiretroviral therapy. Specifically, the research objective is to develop innovative strategies for improved delivery of antiretroviral drugs and other anti-HIV agents to specific cell types or tissue compartments that serve as persistent HIV-producing reservoirs. The majority of research on HIV persistence to date has focused on studies of latently infected resting CD4 T cells that do not actively produce virus. Indeed, most drug intensification and single-genome analysis studies of residual virus have not demonstrated evidence of ongoing viral replication or evolution in the plasma of individuals on optimally suppressive antiretroviral therapy. Nonetheless, emerging evidence suggests that it may be possible for cells in tissues such as the gut to continue to produce low levels of HIV and, perhaps, to transmit virus from cell-to-cell at a low rate. This, in turn, may lead to inflammation, which may also play a role in maintaining the persistent reservoir of HIV.  This lack of control of virus production could, in part, be due to reduced concentrations of antiretrovirals in cells within specific tissue compartments.

Specific Areas of Research Interest

Applications in response to this FOA should propose research to better understand the nature of the persistently active reservoir of HIV and to test innovative approaches to eliminate the reservoir. Investigators may also use an animal model, such as humanized mice or non-human primates, to assess the effect of their proposed strategy on residual reservoirs of persistent HIV/SIV production in the context of optimized antiretroviral therapy. Therapeutics to be employed may include traditional small molecule inhibitors, as well as experimental therapeutics such as peptide or antibody-based agents, or siRNA. Strategies may include the use of novel formulations or delivery methods, the use of therapeutics that concentrate in specific tissues or cell types associated with HIV reservoirs, or the rational design of new drug regimens based on pharmacology in specific tissues and cells that serve as HIV reservoirs.

Specific areas of research interest include, but are not limited to:

  • Studies of ongoing virus production and evolution in tissue reservoirs in the context of suppressive antiretroviral therapy
  • Studies of in vivo cell-to-cell transfer of HIV/SIV in the context of suppressive antiretroviral therapy
  • Studies of intracellular drug concentrations in vivo to define appropriate drug combinations for optimal suppression of virus production and cell-to-cell transmission in tissues
  • Testing of new combinations of existing antiretrovirals to determine optimal tissue penetration
  • Designing “rational intensification” studies using antiretroviral regimens predicted to penetrate persistent reservoirs more efficiently
  • Delivery of antiretrovirals directly to sanctuary sites in the gut or other tissues and testing of the effect on the persistent viral reservoir in the context of suppressive antiretroviral therapy
  • Development of new approaches to target antiretrovirals to specific cell types or tissues (e.g., using nanoparticles)
  • Testing of new antiretrovirals that concentrate intracellularly in specific cell types or tissues or that penetrate the blood-brain barrier more efficiently
  • Development of efficient methods to deliver new classes of inhibitors (e.g., siRNA, zinc-finger nucleases, homing endonucleases, monoclonal antibodies, gene therapy vectors, etc.) to reservoir sites or specific cell types to facilitate the testing of novel HIV eradication strategies in vivo
  • Identification and testing of new strategies for killing or limiting the survival of cells that constitute the active reservoir
  • Use of animal models to demonstrate proof-of-concept for the strategies outlined above
  • Development of new assays to facilitate the studies of active tissue reservoirs outlined above
ELIGIBILITY

Eligible Organizations

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 eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are eligible to apply.

Foreign components, as defined in the NIH Grants Policy Statementare allowed.

Required Registrations

Applicant organizations must complete the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. Applicants must have a valid Dun and Bradstreet Universal Numbering System (DUNS) number in order to begin each of the following registrations.

All Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) must also work with their institutional officials to register with the eRA Commons or ensure their existing eRA Commons account is affiliated with the eRA Commons account of the applicant organization. 

All registrations must be completed by the application due date. Applicant organizations are strongly encouraged to start the registration process at least 4-6 weeks prior to the application due date.

Eligible Individuals (Program Director(s)/Principal Investigator(s))

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.

For institutions/organizations proposing multiple PD(s)/PI(s), visit the Multiple Program Director(s)/Principal Investigator(s) Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF 424 (R&R) Application Guide

CONTACT INFORMATION

Application Submission Contacts

Grants.gov Customer Support (Questions regarding Grants.gov registration and submission, downloading or navigating forms)
Contact Center Phone: 800-518-4726 
Email: support@grants.gov 

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Telephone 301-435-0714
TTY 301-451-5936
Email: GrantsInfo@nih.gov

eRA Commons Help Desk(Questions regarding eRA Commons registration, tracking application status, post submission issues)
Phone: 301-402-7469 or 866-504-9552 (Toll Free)
TTY: 301-451-5939
Email: commons@od.nih.gov 

Scientific/Research Contact(s)

Karl Salzwedel, Ph.D. 
Division of AIDS
National Institute of Allergy and infectious Diseases (NIAID)
Room 4149, MSC-7620
6700B Rockledge Drive
Bethesda, MD 20892-7620
Telephone:  (301) 496-5332
Email: salzwedelkd@mail.nih.gov

Jeymohan Joseph, Ph.D.
National Institute of Mental Health (NIMH)
NSC Building, Room 6219, MSC-9619
6001 Executive Boulevard
Rockville, MD 20852-9619
Telephone:  (301) 443-6100
Email:  jjeymoha@mail.nih.gov 

Peer Review Contact(s)

Examine your eRA Commons account for review assignment and contact information (information appears two weeks after the submission due date).

Financial/Grants Management Contact(s)

Ann Devine
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases (NIAID)
Room 2114, MSC-7614
6700B Rockledge Drive
Bethesda, MD 20892-7614
Telephone:  (301) 402-5601
Email:  adevine@niaid.nih.gov

Rita Sisco
Grants Management Branch
National Institute of Mental Health (NIMH)
NSC Building, Room 6120, MSC-9605
6001 Executive Boulevard
Rockville, MD 20852-6120
Telephone:  301-443-2805
Email:  siscor@mail.nih.gov