Opportunity Information: Apply for RFA MH 14 171
Apply for RFA MH 14 171
- The National Institutes of Health in the education health sector is offering a public funding opportunity titled "Eradication of HIV 1 from CNS Reservoirs Implications for Therapeutics (R21)" and is now available to receive applicants.
- Interested and eligible applicants and submit their applications by referencing the CFDA number(s): 93.242 Mental Health Research Grants 93.279 Drug Abuse and Addiction Research Programs 93.853 Extramural Research Programs in the Neurosciences and Neurological Disorders 93.856 Microbiology and Infectious Diseases Research.
- This funding opportunity was created on Apr 10, 2013 and posted on Apr 10, 2013.
- Applicants must submit their applications by Sep 17, 2013. (Agency may still review applications by suitable applicants for the remaining/unused allocated funding in 2026.)
- Each selected applicant is eligible to receive up to $200,000.00 in funding.
- Eligible applicants include: Nonprofits having a 501(c)(3) status with the IRS, other than institutions of higher education Small businesses Private institutions of higher education Native American tribal governments (Federally recognized) Others (see text field entitled Additional Information on Eligibility for clarification) Special district governments Public and State controlled institutions of higher education Public housing authorities/Indian housing authorities State governments Native American tribal organizations (other than Federally recognized tribal governments) For profit organizations other than small businesses City or township governments Nonprofits that do not have a 501(c)(3) status with the IRS, other than institutions of higher education County governments Independent school districts.
- Other Eligible Applicants include the following Alaska Native and Native Hawaiian Serving Institutions Asian American Native American Pacific Islander Serving Institutions (AANAPISISs) Eligible Agencies of the Federal Government Faith based or Community based Organizations Hispanic serving Institutions Historically Black Colleges and Universities (HBCUs) Indian/Native American Tribal Governments (Other than Federally Recognized) Non domestic (non U.S.) Entities (Foreign Organizations) Regional Organizations Tribally Controlled Colleges and Universities (TCCUs) U.S. Territory or Possession 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 Statement, are allowed.
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Opportunity Summary:
The NIH funding opportunity "Eradication of HIV 1 from CNS Reservoirs: Implications for Therapeutics (R21)" (Funding Opportunity Number RFA-MH-14-171) is a discretionary research grant announcement focused narrowly on one of the hardest remaining barriers to an HIV cure: the persistence of HIV-1 within the central nervous system (CNS) of people whose systemic infection is otherwise well controlled on Highly Active Anti-Retroviral Therapy (HAART). The central idea behind the FOA is that durable remission or eradication strategies cannot be considered complete if they fail to address viral persistence in the brain and other CNS compartments, where drug penetration, immune surveillance, and cell types differ substantially from peripheral blood and lymphoid tissues. The announcement emphasizes innovation and is meant to support early-stage, high-impact projects typical of the NIH R21 mechanism.
The FOA highlights five scientific areas that applicants may pursue, spanning basic through translational research, as long as the work is centered on CNS reservoirs. First, it seeks studies that identify and characterize persistent HIV-1 specifically in CNS-derived cells, with particular attention to macrophages, microglia, and astrocytes, and explicitly in the setting of suppressive antiretroviral therapy. It also allows investigators to examine how substance use may alter persistence in these CNS cell populations, reflecting concern that comorbid drug use could affect neuroinflammation, viral latency, immune responses, adherence patterns, and drug exposure in the CNS. Second, the FOA calls for mechanistic research on how CNS persistence is established over time, how it is maintained during therapy, and how it may reemerge, including how these dynamics relate to the timing of antiretroviral initiation. This includes questions such as whether early ART changes seeding of CNS reservoirs, what cellular or anatomical niches support long-lived infection, and which viral or host pathways enable rebound or reactivation in the CNS even when plasma viral load is suppressed.
Third, the NIH is looking for development or refinement of physiologically relevant animal models and CNS-based cellular assays that more faithfully reproduce HIV-1 persistence and latency under effective HAART. The emphasis on "physiologically relevant" signals interest in models that capture CNS complexity (cell-cell interactions, inflammatory milieu, blood-brain barrier considerations, and CNS pharmacology), rather than simplified systems that may not predict clinical behavior. These models and assays may also incorporate chronic substance use variables when appropriate, again underscoring the programmatic interest in real-world comorbidities that could shape CNS reservoir behavior and treatment response. Fourth, the FOA invites studies that evaluate existing or emerging eradication approaches for their ability to reactivate or otherwise affect persistent HIV in CNS-derived cells like microglia, macrophages, and astrocytes. In practice, this could include examining whether latency-reversing or other cure-directed interventions actually reach the CNS, act on the relevant cell types, and achieve meaningful effects on persistent virus in brain-related compartments rather than only in blood-based assays.
Fifth, and critically, the FOA prioritizes evaluation of CNS toxicity and other adverse impacts of eradication strategies. This reflects a core concern in HIV cure research: interventions designed to flush out or eliminate reservoirs might provoke neuroinflammation, neuronal injury, or other CNS harms, especially if they broadly activate immune pathways, alter glial function, or interact with CNS pharmacology. The announcement therefore encourages projects that do not only ask "does it work?" but also "is it safe for the brain?", including careful assessment of neurotoxicity risks and potential unintended consequences.
In terms of scope and logistics, the opportunity is administered by the National Institutes of Health and is positioned at the intersection of mental health, neuroscience, drug abuse research, and infectious disease/microbiology, as reflected by the listed CFDA numbers (93.242, 93.279, 93.853, 93.856). The award ceiling is listed as $200,000, and there is no cost sharing or matching requirement. The FOA explicitly welcomes applications from both domestic and international settings and notes that multidisciplinary teams are encouraged but not mandatory, signaling openness to collaborations across virology, neuroimmunology, clinical neurology, pharmacology, addiction science, and model development.
Eligibility is broad and includes universities (public and private), nonprofits (including but not limited to 501(c)(3) organizations), for-profit entities (including small businesses and other for-profits), state and local governments, tribal governments and tribal organizations, school districts, public housing authorities/Indian housing authorities, and a wide range of mission-focused institutions such as HBCUs, Hispanic-serving institutions, AANAPISIs, TCCUs, Alaska Native and Native Hawaiian Serving Institutions, and faith-based or community-based organizations. Foreign organizations and foreign institutions are also eligible to apply, and foreign components of U.S. organizations are allowed under NIH policy. Key dates indicate the FOA was posted April 10, 2013, with an original and final closing date of September 17, 2013, and an archive date of October 18, 2013, meaning it is no longer an active opportunity but remains an instructive example of NIH priorities in CNS HIV reservoir research.
Overall, this FOA is aimed at accelerating cure-relevant science where the CNS has historically been underrepresented relative to blood and lymphoid reservoirs. It pushes applicants to directly confront the unique biology of HIV persistence in brain-associated cell types, build better models that reflect HAART-era reality, test whether eradication strategies meaningfully engage CNS reservoirs, and measure neurotoxicity risks carefully so that future cure strategies do not trade viral control for neurological harm.
FAQs: NIH R21 - Eradication of HIV-1 from CNS Reservoirs: Implications for Therapeutics (RFA-MH-14-171)
What is the title and funding opportunity number for this NIH grant?
The opportunity is titled "Eradication of HIV 1 from CNS Reservoirs: Implications for Therapeutics (R21)" and the Funding Opportunity Number (FOA) is RFA-MH-14-171.
What kind of grant mechanism is this opportunity using?
This FOA uses the NIH R21 mechanism, which is intended for early-stage, exploratory, and potentially high-impact research projects with an emphasis on innovation.
What is the main problem this FOA is trying to address?
The FOA targets a key barrier to an HIV cure: the persistence of HIV-1 in central nervous system (CNS) reservoirs (such as the brain and other CNS compartments) in people whose systemic infection is otherwise well controlled on Highly Active Anti-Retroviral Therapy (HAART).
Why is the CNS specifically emphasized in HIV cure research?
The FOA highlights that durable remission or eradication strategies are incomplete if they do not address HIV persistence in the CNS. CNS compartments differ from peripheral blood and lymphoid tissues in drug penetration, immune surveillance, and relevant cell types, making CNS reservoirs a unique scientific and therapeutic challenge.
What types of research does the FOA support?
The FOA supports research spanning basic through translational science, as long as the work is centered on HIV-1 persistence in CNS reservoirs and is consistent with the innovative, high-impact intent of the R21 mechanism.
What scientific areas does the FOA highlight for applicants?
The FOA highlights five areas: (1) identifying and characterizing persistent HIV-1 in CNS-derived cells under suppressive therapy, (2) mechanisms of establishment, maintenance, and reemergence of CNS persistence over time, including timing of antiretroviral initiation, (3) development/refinement of physiologically relevant animal models and CNS-based cellular assays under effective HAART, (4) evaluating eradication approaches for their effects on persistent HIV in CNS-derived cells, and (5) evaluating CNS toxicity and other adverse impacts of eradication strategies.
Which CNS cell types are specifically called out as important in this FOA?
The FOA specifically calls attention to macrophages, microglia, and astrocytes as CNS-derived cell populations where persistent HIV-1 may be identified, characterized, and therapeutically targeted, particularly in the setting of suppressive antiretroviral therapy.
Does the FOA require that studies be conducted under suppressive antiretroviral therapy conditions?
The FOA explicitly emphasizes identifying and characterizing persistent HIV-1 in CNS-derived cells in the setting of suppressive antiretroviral therapy, reflecting the real-world context in which systemic viral load may be controlled while CNS persistence remains a concern.
How does the FOA treat the role of substance use in CNS HIV persistence?
The FOA allows investigators to examine how substance use may alter HIV persistence in CNS cell populations, reflecting concerns that comorbid drug use could affect neuroinflammation, viral latency, immune responses, adherence patterns, and drug exposure in the CNS.
What kinds of mechanistic questions about CNS persistence are encouraged?
The FOA encourages mechanistic work on how CNS persistence is established, maintained during therapy, and reemerges. It also points to questions related to when antiretroviral therapy is initiated, such as whether early ART changes seeding of CNS reservoirs, what cellular or anatomical niches support long-lived infection, and what viral or host pathways enable rebound or reactivation in the CNS despite suppressed plasma viral load.
Are model systems and assays within scope, and what does "physiologically relevant" mean here?
Yes. The FOA calls for development or refinement of physiologically relevant animal models and CNS-based cellular assays that more faithfully reproduce HIV-1 persistence and latency under effective HAART. "Physiologically relevant" signals interest in models that capture CNS complexity (including cell-cell interactions, inflammatory milieu, blood-brain barrier considerations, and CNS pharmacology) rather than overly simplified systems that may not predict clinical behavior.
Can models or assays include chronic substance use variables?
Yes. The FOA notes that models and assays may incorporate chronic substance use variables when appropriate, consistent with the FOA's interest in comorbidities that could shape CNS reservoir behavior and treatment response.
What does the FOA say about testing eradication or cure-directed interventions in the CNS?
The FOA invites studies evaluating existing or emerging eradication approaches for their ability to reactivate or otherwise affect persistent HIV in CNS-derived cells (including microglia, macrophages, and astrocytes). It reflects an interest in whether interventions reach the CNS, act on relevant CNS cell types, and show meaningful effects in brain-related compartments rather than only in blood-based assays.
How important is safety and neurotoxicity in this FOA?
Safety is a priority area. The FOA explicitly prioritizes evaluation of CNS toxicity and other adverse impacts of eradication strategies, emphasizing that cure-directed interventions might provoke neuroinflammation, neuronal injury, or other CNS harms. Projects are encouraged to ask not only whether an approach works, but whether it is safe for the brain, including careful assessment of neurotoxicity risks and unintended consequences.
Which NIH areas or disciplines does this FOA sit within?
The FOA is positioned at the intersection of mental health, neuroscience, drug abuse research, and infectious disease/microbiology, consistent with its focus on CNS reservoirs, neurobiology, substance use considerations, and HIV persistence under therapy.
What CFDA numbers are associated with this opportunity?
The listed CFDA numbers are 93.242, 93.279, 93.853, and 93.856.
What is the award ceiling for this FOA?
The award ceiling is listed as $200,000.
Is cost sharing or matching required?
No. The FOA states there is no cost sharing or matching requirement.
Are multidisciplinary teams required?
Multidisciplinary teams are encouraged but not mandatory. The FOA signals openness to collaborations across areas such as virology, neuroimmunology, clinical neurology, pharmacology, addiction science, and model development.
Who is eligible to apply?
Eligibility is broad and includes public and private universities, nonprofits (including but not limited to 501(c)(3) organizations), for-profit entities (including small businesses and other for-profits), state and local governments, tribal governments and tribal organizations, school districts, public housing authorities/Indian housing authorities, and a wide range of mission-focused institutions such as HBCUs, Hispanic-serving institutions, AANAPISIs, TCCUs, Alaska Native and Native Hawaiian Serving Institutions, and faith-based or community-based organizations.
Are foreign (non-U.S.) organizations eligible to apply?
Yes. The FOA explicitly welcomes applications from both domestic and international settings. Foreign organizations and foreign institutions are eligible to apply.
Are foreign components of U.S. organizations allowed?
Yes. The FOA notes that foreign components of U.S. organizations are allowed under NIH policy.
When was this FOA posted, and what were the closing dates?
The FOA was posted on April 10, 2013. The original and final closing date was September 17, 2013.
Is this FOA still active?
No. The archive date is October 18, 2013, which indicates the opportunity is no longer active.
If the FOA is archived, why is it still useful to review?
Based on the description provided, it remains an instructive example of NIH priorities in CNS HIV reservoir research, including the emphasis on CNS-specific persistence under HAART, improved CNS-relevant models, testing cure strategies in CNS compartments, and careful evaluation of neurotoxicity.
What makes this FOA "narrowly focused" compared to other HIV cure opportunities?
It is narrowly focused on HIV-1 persistence specifically within the CNS in individuals with systemic viral control on HAART, and it emphasizes CNS-derived cell types, CNS-specific modeling, and CNS safety considerations rather than primarily blood- or lymphoid-focused reservoir work.
Does the FOA support both basic and translational research?
Yes. The FOA describes a range spanning basic through translational research, as long as the work is centered on CNS reservoirs.
What CNS-specific challenges does the FOA imply researchers should account for?
The FOA points to CNS-specific issues including differences in drug penetration, immune surveillance, distinct CNS cell types involved in persistence, blood-brain barrier considerations, inflammatory milieu, and CNS pharmacology, all of which can affect persistence and therapeutic performance in the CNS.
What is the overarching goal of the FOA?
The overarching goal is to accelerate cure-relevant science that directly addresses HIV persistence in CNS reservoirs by understanding CNS reservoir biology, building more realistic HAART-era CNS models, testing whether eradication strategies truly engage CNS reservoirs, and carefully assessing neurotoxicity so that future cure strategies do not cause neurological harm.
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