Key Dates

Related Announcements

• May 08, 2023 - NINDS Postdoctoral Mentored Career Development Award (K01 Clinical Trial Required). See NOFO PAR-23-142
• May 08, 2023 - NINDS Postdoctoral Mentored Career Development Award (K01 No Independent Clinical Trial Allowed). See NOFO PAR-23-143
• January 26, 2023 - Ruth L. Kirschstein National Research Service Award (NRSA) Institutional Research Training Grant (Parent T32). See NOFO PA-23-048
• December 13, 2022 - Clinical Studies of Mental Illness (Collaborative R01) (Clinical Trial Optional). See NOFO  PAR-23-050
• September 8, 2021 - Emerging Global Leader Award (K43 Independent Clinical Trial Required). See NOFO   PAR-21-251
• September 8, 2021  - Emerging Global Leader Award (K43 Independent Clinical Trial Not Allowed). See NOFO  PAR-21-252 
• May 10, 2021 - NIMH Exploratory/Developmental Research Grant (R21 Clinical Trial Not Allowed). See NOFO  PA-21-235
• May 19, 2021 - Academic Research Enhancement Award for Undergraduate-Focused Institutions (R15 Clinical Trial Required). See NOFO PAR-21-154
• May 19, 2021 - Academic Research Enhancement Award for Undergraduate-Focused Institutions (R15 Clinical Trial Not Allowed). See NOFO PAR-21-155
• May 10, 2021 - Joint NINDS/NIMH Exploratory Neuroscience Research Grant (R21 Clinical Trial Optional). See NOFO PA-21-219
• May 7, 2021  - NIMH Research Education Mentoring Program for HIV/AIDS Researchers (R25 Clinical Trial Not Allowed). See NOFO  PAR-21-228
• April 23, 2021 - NINDS Faculty Development Award to Promote Diversity in Neuroscience Research (K01 Independent Clinical Trial Not Allowed). See NOFO PAR-21-234
• April 8, 2021 - NINDS Faculty Development Award to Promote Diversity in Neuroscience Research (K01 Clinical Trial Required). See NOFO PAR-21-153
• October 28, 2020  - Ruth L. Kirschstein National Research Service Award (NRSA) Individual Predoctoral Fellowship to Promote Diversity in Health-Related Research (Parent F31-Diversity). See NOFO  PA-21-052
• October 26, 2020 - Ruth L. Kirschstein National Research Service Award (NRSA) Individual Postdoctoral Fellowship (Parent F32). See NOFO  PA-21-048
• October 25, 2020 - Ruth L. Kirschstein National Research Service Award (NRSA) Individual Fellowship for Students at Institutions Without NIH-Funded Institutional Predoctoral Dual-Degree Training Programs (Parent F30). See NOFO PA-21-050 
• October 21, 2020  - Ruth L. Kirschstein National Research Service Award (NRSA) Individual Predoctoral Fellowship (Parent F31). See NOFO  PA-21-051
• October 15, 2020 - NINDS Ruth L. Kirschstein National Research Service Award (NRSA) for Training of Postdoctoral Fellows (F32 Clinical Trial Not Allowed). See NOFO PAR-21-032
• May 12, 2020 - Mentored Clinical Scientist Research Career Development Award (Parent K08 Independent Clinical Trial Required). See NOFO PA-20-202
• May 12, 2020  - Mentored Clinical Scientist Research Career Development Award (Parent K08 Independent Clinical Trial Not Allowed). See NOFO PA-20-203
• May 12, 2020  - Mentored Patient-Oriented Research Career Development Award (Parent K23 Independent Clinical Trial Not Allowed). See NOFO PA-20-205
• May 12, 2020  - Mentored Patient-Oriented Research Career Development Award (Parent K23 Independent Clinical Trial Required). See NOFO PA-20-206
•  
• May 7, 2020 - NIH Small Research Grant Program (Parent R03 Clinical Trial Not Allowed). See NOFO PA-20-200
• May 6, 2020  - Mentored Research Scientist Development Award (Parent K01-Independent Clinical Trial Required). See NOFO PA-20-176
• May 6, 2020 - Midcareer Investigator Award in Patient-Oriented Research (Parent K24 Independent Clinical Trial Not Allowed). See NOFO - PA-20-186 
• May 6, 2020 - Mentored Research Scientist Development Award (Parent K01--Independent Clinical Trial Not Allowed). See NOFO PA-20-190
• May 6, 2020 - Midcareer Investigator Award in Patient-Oriented Research (Parent K24 Independent Clinical Trial Required). See NOFO  PA-20-193
•  
• May 5, 2020 - Research Project Grant (Parent R01 Clinical Trial Required). See NOFO PA-20-183
• May 5, 2020 - NIH Research Project Grant (Parent R01 Basic Experimental Studies with Humans Required). See NOFO PA-20-184 
• May 5, 2020  - NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed). See NOFO PA-20-185
• May 5, 2020 - NIH Pathway to Independence Award (Parent K99/R00 Independent Clinical Trial Required). See NOFO PA-20-187 
• May 5, 2020 - NIH Pathway to Independence Award (Parent K99/R00 Independent Clinical Trial Not Allowed). See NOFO - PA-20-188 

Issued by

National Institute of Mental Health (NIMH)

National Institute of Neurological Disorders and Stroke (NINDS)

Purpose

The goal of this initiative is to understand the heterogeneity of Central Nervous System (CNS) outcomes in people with HIV (PWH) and to support clinical research studies to aid in the identification/validation of actionable biosignatures of adverse CNS outcomes in people with HIV. Multidisciplinary research teams and collaborative alliances are encouraged but not required.

Background:

Central Nervous System complications associated with HIV continue  to persist in people with HIV (PWH) despite effective antiretroviral therapy (ART). Although excellent virologic control in the periphery and brain has been achieved, CNS disease including neurologic, neurocognitive, and mental health problems are observed. While the prevalence of mental health problems such as depression and anxiety disorders are high in PWH, CNS disease research has been traditionally focused on cognitive impairment and there is a lack of understanding of the biological mechanisms underlying mental health disorders.  Among PWH, both HIV and ART cause inflammatory/immune-related changes in the CNS and the periphery. In addition, social and environmental factors such as violence, stigma, discrimination, and stress, which are common among people living with HIV, also contribute to disruption of the neurotransmitter/ neuroinflammatory homeostasis in the brain. To-date there is a paucity of studies that examine the impact of somatic and non-somatic causes of adverse CNS outcomes in people living with HIV. A better understanding of the unique mechanisms underlying these cognitive and mental health related disorders in PWH is an area of interest of this Notice of Special Interest (NOSI). Such studies may potentially lead to novel interventions to improve outcomes among PWH.

Development of biological measures to assess CNS disease associated with HIV is a high research priority. Recent technological advances in mass spectrometry, proteomics and systems biology may be harnessed to enable discovery of disease progression tracking biomarkers. To better understand the neuropathogenesis and the etiology of clinical outcomes observed in PWH on modern ART regimens, studies examining neuronal networks, neural circuits and pathways have the potential to provide a framework to develop quantitative biomedical diagnostic tools that reflect the true nature and extent of CNS impairment, thereby diminishing the reliance on complicated subjective neuropsychiatric batteries. This NOSI encourages neuroimaging studies and discovery of mechanistic biomarkers both to understand the mechanisms of HIV-associated CNS disease and to identify diagnostic signatures. Definitional criteria and diagnosis of HIV-associated CNS disease have largely relied on outcomes inferred from neuropsychological test performance. Several recent reports have highlighted the heterogeneity of HIV-associated CNS disease outcomes, but the existing diagnostic methods discount the heterogeneity and classify disease according to the degree of impairment. To understand the heterogeneity of CNS disease observed in the current era, there is a need to explore other diagnostic modalities such as domain-based approaches. Using a domain-based framework such as Research Domain Criteria (RDoC) can assist the field in understanding the varying degrees of disease and heterogeneity seen in patients in the context of ART and co-morbidities. RDoC is a research framework that integrates many levels of information (from genomics and circuits to behavior and self-reports) in order to explore basic dimensions of functioning that span the full range of human behavior from normal to abnormal (https://www.nimh.nih.gov/research/research-funded-by-nimh/rdoc/index.shtml). 

Areas of Research Interest:

The research areas that are pertinent to this NOSI include, but are not limited to:

Clinical studies of CNS complications in PWH

• Epidemiology studies to understand the phenotype and heterogeneity of CNS outcomes in people living with HIV in the context of ART and co-morbidities across the lifespan;
• Studies of the biological, behavioral and psychosocial mechanisms of common mental disorders and other CNS complications in PWH;
• Studies of functional changes in brain neurochemistry and neuroendocrine milieu that lead to adverse CNS outcomes in people with HIV on stable ART;
• Studies that investigate the impact of HIV and associated immune dysfunction on brain circuits and networks regulating mood, cognition and behavior;
• Studies that integrate genetic, neurobiological, imaging, behavioral, psychosocial and clinical data to characterize the nature and mechanisms of CNS complications in PWH;
• Studies to adapt existing diagnostic neuroimaging and electrophysiology-based methods to measure and monitor activity of neuron ensembles and pathways in PWH that can augment our understanding of the disease etiology;
• Develop and utilize tailored cognitive assessments using the RDoC framework in conjunction with other biological measures such as neuroimaging and immune profiles to identify pathways and mechanisms associated with CNS disease outcomes in PWH;
• Studies to Identify novel molecular biomarkers in cerebrospinal fluid (CSF) and blood linked with milder and chronic forms of HIV-associated CNS complications using state-of-the art techniques including genomics, proteomics, metabolomics, systems biology and neuroimaging;
• Studies to identify mechanisms by which gut microbiota and gut immune system altered by HIV impact CNS outcomes in PWH across the lifespan;
• Studies to identify mechanistic biological signatures of immune dysfunction linked with adverse CNS outcomes in the context of HIV;
• Research on pharmacologic interactions of therapeutic drugs including ART and other relevant medications on CNS outcomes in PWH.

NINDS Research Interests:

NINDS supports research on the brain and nervous system and uses that knowledge to reduce the burden of neurological disease. In the context of HIV disease and for the purposes of this notice, the NINDS is interested in the majority of the research areas identified above. Research of particular interest would include: studies of the mechanisms by which chronic HIV exacerbates long term blood-brain barrier (BBB) damage and cerebrovascular dysfunction in the context of stroke and vascular contributions to cognitive impairment and dementia (VCID); studies of the mechanisms by which chronic HIV might prime the CNS for neurodegeneration including in the context of AD/ADRD; research focused on potential interactions between chronic HIV infection and other neurological disorders within the mission of NINDS and projects that address the mechanisms of HIV-associated peripheral neuropathy/chronic pain. Applications that are solely interested in mental health and psychiatric outcomes (using RDoC framework) will not be supported by NINDS. NINDS strongly prefers the incorporation of additional multidimensional measures of neurological function, such as the NIH Toolbox for the assessment of cognitive, motor, and sensory function, in combination with other mental health-related measures. In addition, only mechanistic clinical trials and Basic Experimental Studies with Humans (BESH) will be supported by the NINDS under this NOSI. Clinical trials that seek to answer specific questions about safety, tolerability, clinical efficacy, effectiveness, clinical management, and/or implementation of pharmacologic, behavioral, biologic, surgical, or device (invasive or non-invasive) interventions will not be supported under this NOSI.

NINDS urges investigators to follow the NIH guidance for rigor and transparency in grant applications (https://grants.nih.gov/policy/reproducibility/guidance.htm) and additionally recommends the research practices described at https://www.ninds.nih.gov/Funding/grant_policy to ensure that robust experiments are designed, potential experimenter biases are minimized, results and analyses are transparently reported, and results are interpreted carefully. These recommended research practices include, where applicable: rationale for the chosen model(s) and primary/secondary endpoints, clear descriptions of tools and parameters, blinding, randomization, ensuring adequate sample size, pre-specified inclusion/exclusion criteria, handling of missing data and outliers, appropriate controls, preplanned analyses, appropriate quantitative techniques, clear indication of exploratory vs. confirmatory components of the study, consideration of limitations, and plans for transparent reporting of all methods, analyses, and results so that other investigators can evaluate the quality of the work and potentially perform replications

Note:

Prospective applicants are strongly encouraged to contact the Scientific Program Contacts listed below before preparing an application to discuss the relevance of the proposed research to the Institute's research priorities.

Applications submitted to this NOSI can include studies using multidisciplinary approaches involving in-vitro and in-vivo models in addition to the clinical component. Applications to this NOSI are strongly encouraged to integrate at least two levels of analysis (e.g. behavior/cognition, neural circuits, genetics, molecular and cellular processes) and use approaches to study discrete neurobiologically-linked behavioral constructs (RDoC Framework, NIH Toolbox, and/or Neuro-QoL-based assessments).  Also, guidelines and priorities in the field of stress biology research as detailed in NOT-MH-18-058 apply to applications submitted to this NOSI. 

The use of human specimen resources from large NIH-funded HIV-related studies are  encouraged.

Examples of such studies include, but are not limited to:

• MACS/WIHS Combined Cohort Study
• CNS HIV Antiretroviral Therapy Effects Research (CHARTER)
• AIDS Clinical Trials Group (ACTG)  
• National NeuroAIDS Tissue Consortium (NNTC)

This notice applies to due dates on or after September 7, 2023 and subsequent receipt dates through September 8, 2026.

Submit applications for this initiative using one of the following Notices of Funding Opportunities announcements (NOFOs) or any reissues of these announcements through the expiration date of this notice.

 All instructions in the SF424 (R&R) Application Guide and the funding opportunity announcement used for submission must be followed, with the following additions:

• For funding consideration, applicants must include “NOT-MH-23-255” (without quotation marks) in the Agency Routing Identifier field (box 4B) of the SF424 R&R form. Applications without this information in box 4B will not be considered for this initiative.

Applications nonresponsive to terms of this NOSI will be withdrawn from consideration for this initiative.

Inquiries

Please direct all inquiries to the Scientific/Research, Peer Review, and Financial/Grants Management contacts in Section VII of the listed notice of funding opportunity.

 Scientific/Research Contact(s)

Vasudev R. Rao, MBBS, MS.
National Institute of Mental Health (NIMH)
Telephone: 301-825-3259
Email: vasudev.rao@nih.gov

William Daley, Ph.D.
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-496-1431
Email: william.daley@nih.gov

Financial/Grants Management Contact(s)

Rita Sisco
National Institute of Mental Health (NIMH)
Telephone: 301-443-2805
Email:siscor@mail.nih.gov

Chief Grants Management Officer
National Institute of Neurological Disorders and Stroke (NINDS)
Email: ChiefGrantsManagementOfficer@ninds.nih.gov