Key Dates

Related Announcements

PAR-22-201 - NIDA Program Project Grant Applications (P01 Clinical Trial Optional)

PA-20-185 - NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed)

PA-20-184 - Research Project Grant (Parent R01 Basic Experimental Studies with Humans Required)

PA-20-183 - Research Project Grant (Parent R01 Clinical Trial Required)

PA-20-194 - NIH Exploratory/Developmental Research Grant Program (Parent R21 Clinical Trial Required)

PA-20-195 - NIH Exploratory/Developmental Research Grant Program (Parent R21 Clinical Trial Not Allowed)

PA-20-196 - NIH Exploratory/Developmental Research Grant Program (Parent R21 Basic Experimental Studies with Humans Required)

PAR-20-224 - Avenir Award Program for Research on Substance Use Disorders and HIV/AIDS (DP2 Clinical Trial Optional)

PAR-20-221 - NIDA Avant-Garde Award Program for HIV/AIDS and Substance Use Disorder Research (DP1, Clinical Trial Optional)

PA-20-187 - NIH Pathway to Independence Award (Parent K99/R00 Independent Clinical Trial Required)

PA-20-188 - NIH Pathway to Independence Award (Parent K99/R00 Independent Clinical Trial Not Allowed)

PA-20-189 - NIH Pathway to Independence Award (Parent K99/R00 Independent Basic Experimental Studies with Humans Required)

PA-20-190 - Mentored Research Scientist Development Award (Parent K01 - Independent Clinical Trial Not Allowed)

PA-20-191 - Mentored Research Scientist Development Award (Parent K01 Independent Basic Experimental Studies with Humans Required)

PA-20-176 - Mentored Research Scientist Development Award (Parent K01 - Independent Clinical Trial Required)

PA-20-208- Substance Use/Substance Use Disorder Dissertation Research Award (R36 - Clinical Trials Optional)

PAR-19-345 - NIDA Program Project Grant Applications (P01 Clinical Trial Optional)

PAR-19-134 - Research Enhancement Award Program (REAP) for Health Professional Schools and Graduate Schools (R15 Clinical Trial Not Allowed)

PA-20-186 - Midcareer Investigator Award in Patient-Oriented Research (Parent K24 Independent Clinical Trial Not Allowed)

PA-20-192 - Midcareer Investigator Award in Patient-Oriented Research (Parent K24 Independent Basic Experimental Studies with Humans Required)

Issued by

National Institute on Drug Abuse (NIDA)

Purpose

Purpose

The goal of this Notice of Special Interest [NOSI] is to support research that will define and validate a set(s) of molecular biomarkers and/or bio-signatures indicating the degree of loss of functional reserve, or of resilience of the host defense mechanisms in people with substance use disorders (SUDs) who acquired HIV (PWH) and are on antiretroviral therapy (ART).

Background

A signature biomarker of a compromised immune system in HIV infection is the number of CD4 T-cells. As HIV infection progresses, the blood count of CD4 T-cells declines from its normal of 500 1500 cells/mm³. A CD4 blood count below 200 is a diagnostic indicator of AIDS. Thus, the CD4 count enables a clinical test for HIV infection, the progression towards developing AIDS, or the ability of treatment regimens such as anti-retroviral therapies to prevent disease progression. However, HIV infection can induce immunological, neurological, behavioral, and cognitive deficits, even when the detrimental effects of viral infection on the immune system CD4 counts are managed by ART. These HIV-induced complications might be further exacerbated in the presence of additional insults, such as SUDs. The availability of Well-validated biomarkers or signatures are would greatly improve the clinical diagnosis and evaluation of the medical consequences and complications that arise as a result of HIV infection acquired in the presence of SUDs, in comparison to complications in PWH consequently taking drugs.

HIV infection, anti-retroviral therapy (ART) to treat HIV infection, and chronic use of drugs impact biological homeostasis of intrinsic host defense mechanisms predictably by inducing molecular changes in the expression or activation of both pro- and anti-inflammatory complexes, and by altering the balance of neuroprotective and neurodegenerative mechanisms. Studies of biomarker exploration are primarily aimed at mediators of host surveillance systems that are reactively activated in response to foreign insults, such as the increased expression of pro-inflammatory or neurodegenerative molecules associated with disease conditions. However, it is equally important to explore as biomarkers: 1) changes to host defense mechanisms associated with inherent anti-inflammatory or neuroprotective actions, and 2) the interactive dynamics between intrinsic destructive and protective mechanisms in disease states. Furthermore, validation of the specificity, sensitivity, accuracy and stability of potential biomarkers is essential. The intent of this NOSI is to encourage research projects that explore both destructive and protective responses as possible biomarkers and/or signatures of brain and peripheral neural complications due to HIV infection and SUDs.

Applicants should consider future application of biomarkers in clinical diagnosis. Thus, it is essential that research applications will conduct comparative and comprehensive assessments of immune, neural and neuroendocrine factors as biomarkers or signatures from body fluids such as blood, saliva or cerebral spinal fluid (CSF), or from non-invasive imaging modalities. The candidate biomarkers/bio-signatures should be physiological indicators of the degree of immune activation/inflammation, of protective and destructive responses, and/or aspects of functional resiliency that are symptomatic of cognitive deficits, maladaptive behaviors or neurological disorders that result from the co-morbid condition of HIV infection and substance use. The ultimate goal will be to support future clinical assay development based on the identified and validated biomarkers and bio-signatures to improve the diagnosis of disease states and treatment of HIV infection and comorbidity of substance use or SUDs.

Research Objectives:

The NOSI fosters biomarker and signature identification and validation that could advance the clinical assessment of the degree of deterioration or damage, of functional reserve, and of resilience of host defense mechanisms, towards HIV infection and comorbidity of HIV with substance use disorders (SUDs). Identified candidate biomarkers/signatures are expected to help with the development of assays for clinical lab test that may inform assessment of early dysfunction, status of disease progression, disease prognosis and ultimately the response to treatment.

Applications submitted in response to this NOSI should propose studies involving human subjects or utilize clinically-translatable animal models of neuroHIV. A responsive, multi-domain profiling research application might propose: 1) to screen for the expression of immune, neural and neuroendocrine factors, including cellular exosomes, in both CSF and blood, 2) to quantify the physiological levels of promising candidate molecules, proteins, or biological signatures, 3) to validate the specificity, sensitivity and accuracy of candidate biomarkers and signatures in informing neuroHIV disease progression and/or the presence of neurological and cognitive complications caused by HIV infection and comorbidity of substance use or SUDs, and 4) to differentiate comparatively validated molecular biomarkers and/or bio-signatures that may distinguish effects of drugs in PWH with or without history of SUDs.

Biomarkers or bio-signatures may be derived from the analysis of blood/plasma, CSF, or imaging modalities. Identification may include molecular changes in the expression or activation of pro- and anti-inflammatory complexes represented by cytokine/chemokine families, the balance of protective and destructive factors (such as brain-derived neurotrophic factor, adenosine, endocannabinoids, endogenous opioids; C-reactive proteins, amyloids, Tau protein, reactive oxygen species, monocyte activation markers like sCD163, and glial fibrillary acidic protein), and exosomes.

Applicants should consider the following in preparing research applications responsive to this announcement:

1. Apply causality design when scientifically feasible to illustrate specific processes and links of cannabinoids and/or endoCB to HIV-associated persistent inflammation, which can include genetic, immunological, or pharmacological approaches

2. Biomarkers and bio-signatures should be validated for their specificity, sensitivity, accuracy and stability as indicators of neurological, behavioral, and cognitive disorders.

3. The physiological value(s) of candidate biomarkers should be quantitated in healthy control, and levels assessed for the ability to predict the degree of disease progression and treatment response.

Other application considerations:

• Variables selected for analysis should be justified based upon well documented relevance to HIV-induced deteriorations and complications. For example, tests of attention or memory assessment should be relevant to HIV-associated pathogenesis
• For human studies, stratification of research subjects should be justified.

Application and Submission Information

This notice applies to due dates on or after June 5, 2021 and subsequent receipt dates through September 8, 2024.

Submit applications for this initiative using one of the following funding opportunity announcements (FOAs) or any reissues of these announcement through the expiration date of this notice.

• PA-20-185 - NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed)
• PA-20-184 - Research Project Grant (Parent R01 Basic Experimental Studies with Humans Required)
• PA-20-183 - Research Project Grant (Parent R01 Clinical Trial Required)
• PA-20-194 - NIH Exploratory/Developmental Research Grant Program (Parent R21 Clinical Trial Required)
• PA-20-195 - NIH Exploratory/Developmental Research Grant Program (Parent R21 Clinical Trial Not Allowed)
• PA-20-196 - NIH Exploratory/Developmental Research Grant Program (Parent R21 Basic Experimental Studies with Humans Required)
• PAR-20-224(DP2) - Avenir Award Program for Research on Substance Use Disorders and HIV/AIDS (DP2 Clinical Trial Optional)
• PAR-20-221(DP1) - NIDA Avant-Garde Award Program for HIV/AIDS and Substance Use Disorder Research (DP1, Clinical Trial Optional)
• PA-20-187 - NIH Pathway to Independence Award (Parent K99/R00 Independent Clinical Trial Required)
• PA-20-188 - NIH Pathway to Independence Award (Parent K99/R00 Independent Clinical Trial Not Allowed)
• PA-20-189 - NIH Pathway to Independence Award (Parent K99/R00 Independent Basic Experimental Studies with Humans Required)
• PA-20-190 - Mentored Research Scientist Development Award (Parent K01 - Independent Clinical Trial Not Allowed)
• PA-20-191 - Mentored Research Scientist Development Award (Parent K01 Independent Basic Experimental Studies with Humans Required)
• PA-20-176 - Mentored Research Scientist Development Award (Parent K01 - Independent Clinical Trial Required)
• PA-20-208(R36) - Substance Use/Substance Use Disorder Dissertation Research Award (R36 - Clinical Trials Optional)
• PAR-19-345(P01) - NIDA Program Project Grant Applications (P01 Clinical Trial Optional)
• PAR-19-134 - Research Enhancement Award Program (REAP) for Health Professional Schools and Graduate Schools (R15 Clinical Trial Not Allowed)
• PA-20-186 - Midcareer Investigator Award in Patient-Oriented Research (Parent K24 Independent Clinical Trial Not Allowed)
• PA-20-192 - Midcareer Investigator Award in Patient-Oriented Research (Parent K24 Independent Basic Experimental Studies with Humans Required)

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-DA-21-014 (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 not be considered for the NOSI initiative.

Inquiries

Scientific/Research Contact(s)

Yu (Woody) Lin
National Institute on Drug Abuse

Division of Neuroscience and Behavior

Telephone: 301-435-1318
Email: [email protected]

Financial/Grants Management Contact(s)

Lennin F. Greenwood
National Institute on Drug Abuse (NIDA)
Telephone: 301-827-6686
Email: [email protected]