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Evaluation of Neurobiological Mechanisms Mediating the Effect of Immune Activation on Neurocognitive Impairment and the Role of Psychosocial Factors Among Women Living with HIV

Award Number: R01MH131177
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/13/2022
PERIOD OF PERFORMANCE END DATE: 06/30/2027

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Evaluation of Neurobiological Mechanisms Mediating the Effect of Immune Activation on Neurocognitive Impairment and the Role of Psychosocial Factors Among Women Living with HIV - PROJECT ABSTRACT/SUMMARY. The proposed R01 is built upon the premise that: 1) Cognitive impairment persists even in the context of HIV viral suppression; 2) women living with HIV experience disproportionate burden of cognitive impairment and have higher rates of, and stronger associations with, many of the underlying risk factors for cognitive impairment, as well as unique risk factors; 3) immune activation persists in the context of viral suppression; 4) immune activation (e.g., Interleukin[IL]-6, sCD163) is a consistent risk factor of cognitive impairment in HIV; 5) neurobiological pathways affecting cognitive functions are activated by HIV directly and indirectly through immune activation; 6) factors such as depression and substance use impair cognitive functions and are associated with heightened immune activation, likely both directly and indirectly through reduced antiretroviral therapy levels. By leveraging the strong infrastructure of the Women's Interagency HIV Study, including existing behavioral data and specimen, the current longitudinal study will fill significant gaps in the field by examining the role of the neurobiological pathways whereby chronic immune activation leads to cognitive impairment phenotypes in a large phenotypically well-defined group of women living with HIV. In a highly cost-effective approach, we will use existing biospecimen to assess biomarkers of chronic immune activation and neurobiological pathways and link them to existing neuropsychological assessments among N=500 women living with HIV aged 26 and older (Median age = 50) at 3 time points, to assess the following aims: Aim 1. To examine neurobiological pathways mediating the link between chronic immune activation and cognitive impairment phenotypes in women living with HIV. Aim 2. To identify modifiable risk factors (substance use, depression) affecting immune activation and neurobiological pathways. Aim 3. To examine the role of antiretroviral therapy hair levels in mediating the effect of the risk factors in Aim 2 on immune activation and neurobiological pathway biomarkers. Impact. The results of this study will have several important clinical implications for the prevention and treatment of cognitive impairment in women living with HIV, including behavioral and pharmacological therapies. Understanding the unique impact of biomarkers on cognitive outcomes will provide guidance on clinical intervention targets (e.g., immune therapy, dopamine reuptake inhibitors). Understanding the role of modifiable risk factors in modulating immune activation and neurobiological pathways and the mediating role of antiretroviral therapy adherence level, will inform behavioral intervention strategies (e.g., resilience, mental health), which may be particularly ideal intervention targets to curb the inflammatory cascade leading to cognitive impairment.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $632,167 )
2026	2026	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH STREET	BIRMINGHAM	AL	35294	JEFFERSON	USA	Mental Health Research Grants	000	5	7/8/2026	NON-COMPETING CONTINUATION	$632,167
														Subtotal = $632,167

Issue Date FY: 2025 ( Subtotal = $656,824 )
2025	2025	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH STREET	BIRMINGHAM	AL	35294	JEFFERSON	USA	Mental Health Research Grants	000	4	7/23/2025	NON-COMPETING CONTINUATION	$656,824
														Subtotal = $656,824

Issue Date FY: 2024 ( Subtotal = $661,886 )
2024	2024	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH STREET	BIRMINGHAM	AL	35294	JEFFERSON	USA	Mental Health Research Grants	000	3	6/20/2024	NON-COMPETING CONTINUATION	$661,886
														Subtotal = $661,886

Issue Date FY: 2023 ( Subtotal = $672,268 )
2023	2023	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Mental Health Research Grants	000	2	8/10/2023	NON-COMPETING CONTINUATION	$672,268
														Subtotal = $672,268

Issue Date FY: 2022 ( Subtotal = $711,991 )
2022	2022	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Mental Health Research Grants	000	1	9/13/2022	NEW	$711,991
														Subtotal = $711,991

Grand Total All Awards = $3,335,136

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Evaluation of Neurobiological Mechanisms Mediating the Effect of Immune Activation on Neurocognitive Impairment and the Role of Psychosocial Factors Among Women Living with HIV

Award Number: R01MH131177

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 09/13/2022

PERIOD OF PERFORMANCE END DATE: 06/30/2027

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