Related Announcements

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

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

PA-20-195 - 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)

Issued by

National Institute on Drug Abuse (NIDA)

All applications to this funding opportunity announcement should fall within the mission of the Institutes/Centers. The following NIH Offices may co-fund applications assigned to those Institutes/Centers.

Office of Research on Women's Health (ORWH)

Purpose

Compared to men, women are often more likely to develop HIV-associated neurocognitive impairments. The purpose of this notice is to inform potential applicants of NIDA’s special interest in understanding the neurobiological bases for sex or gender-specific differences in HIV-associated neurocognitive disorders. This information can be used for targeted therapeutics and optimization of treatment options in HIV positive individuals with substance use disorders.

Background and Research Objectives

HIV-associated neurocognitive disorders (HAND) remain frequent especially in Western countries in a significant number of HIV-positive individuals on anti-retroviral therapy (ART). The prevalence of HAND is progressively increasing with the increased lifespan of HIV-positive individuals. Despite the success of antiretroviral therapy for the prevention and treatment of HIV/AIDS, the development of HAND impairs the quality of life. It has been estimated that approximately 30-50% of people living with HIV [PWH] on ART will demonstrate neurocognitive impairments. Furthermore, substance use disorders [SUD] are a common co-morbidity in people living with HIV and significantly exacerbate cognitive deficits.

The type of cognitive impairment due to HIV is highly variable in PWH with deficits observed in a range of cognitive domains although executive function and memory deficits are most common. Notably, compared to men, women are often more likely to develop HIV-associated neurocognitive impairments. Moreover, the enhanced vulnerability to HAND in females occurs in substance-dependent populations of people living with HIV. In addition to sex differences in the incidence of HAND, there are differences in the pattern of cognitive impairments between men and women living with HIV. For instance, in male-dominated HIV cohorts, the cognitive domains that are predominantly affected are complex attention and executive functioning. In contrast, in women living with HIV, deficits have been predominantly reported in learning and memory performance, speed of information processing and motor functioning. Sex differences in memory and cognition have also been demonstrated in preclinical studies using HIV-1 Tg26 mice. In humans, there is evidence that the enhanced vulnerability to HAND in females is associated with psychosocial factors, such as the level of education and socio-economic status. However, little is known about the neurobiological basis for the sexual dimorphism in HAND.

This notice is targeted at understanding the neurobiological mechanisms for sex-specific differences in HAND and the impact of co-occurring SUD using behavioral, cellular, circuit, genetic, molecular, imaging and/or pharmacological approaches. The knowledge obtained can be used for optimization of treatment options for HAND in HIV positive individuals with substance use disorders.

Questions of research interest include, but are not limited to the following:

• What are the precise differences in the development and expression of HIV-associated neurocognitive disorders in males versus females? How is this altered with acute or chronic exposure to addictive drugs.
• What are the sex differences in neuronal activity in discrete brain regions, neurotransmitter systems and neural circuits in HAND and how is this altered with exposure to addictive substances?
• What is the role of gonadal hormones in sex differences in the development and/or expression of HAND? This may include the impact of exogenous hormone therapy in individuals undergoing gender-reaffirming procedures. Are these the result of organizational or activational actions?
• How do environmental factors (e.g., enriched versus non-enriched environment) interact with and influence neurobiological mechanisms that contribute to sex differences in the development of HAND?

Application and Submission Information

This notice applies to due dates on or after February 5, 2022 and subsequent receipt dates through January 8, 2025. 

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 NIH Research Project Grant (Parent R01 Basic Experimental Studies with Humans Required)

  PA-20-195 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)

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-22-047” (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)

Sunila Nair, PhD
National Institute on Drug Abuse (NIDA)
Telephone: 301-827-6832
Email: [email protected]