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Impacts of drug abuse-mediated inflammatory perturbations on affinity maturation of anti-CD4 autoantibodies and poor immune reconstitution from ART in HIV

Award Number: R01DA059854
ORGANIZATION: NATIONAL INSTITUTE ON DRUG ABUSE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/30/2024
PERIOD OF PERFORMANCE END DATE: 05/31/2029

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Impacts of drug abuse-mediated inflammatory perturbations on affinity maturation of anti-CD4 autoantibodies and poor immune reconstitution from ART in HIV - ABSTRACT This resubmitted proposal is in response to RFA-DA-25-012 (reissue of RFA-DA-24-003) for “Antibody- mediated enhancement of HIV infection/replication following B-cell responses can result in depletion and blunted recovery of CD4+ T-cells and poor immune recovery despite suppressive ART. How these immune components in the context of HIV infection and substance use disorder contribute to the pathology of both conditions represents a significant knowledge gap. Studies focused on inflammasome cascades and pathogenic antibodies mediated by chronic drug use and HIV infection are warranted”. About 25% HIV patients under anti-retroviral therapy (ART) fail to recover CD4+ T cell counts to a level comparable to healthy people. Because CD4+ T cell is critical for immune response to foreign pathogens, it is critical to develop new medications to recover CD4+ T cell counts to reduce co-morbidity and mortality in HIV. Our preliminary studies reveal anti-CD4 autoantibodies to be increased in HIV+ drug abusers and to play a key role in inducing CD4+ T cell death. How cocaine (proinflammation) and cannabis (anti-inflammation) use affect B cell function, pathogenic anti-CD4 autoantibody development, and CD4+ T cell recovery from ART in PWH remains unclear, thus, we propose two aims here: Aim 1. Determine mechanisms of affinity maturation and CD4 recognition for anti-CD4 autoantibodies presenting ADCC activity in HIV+ drug users. Aim 2. Determine drug use-mediated B cell perturbations, anti-CD4 autoantibody production, and HIV immunopathogenesis.


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: 2025 ( Subtotal = $697,735 )
2025	2025	THE MEDICAL UNIVERSITY OF SOUTH CAROLINA	179 ASHLEY AVE	CHARLESTON	SC	29425	CHARLESTON	USA	Drug Use and Addiction Research Programs	001	2	5/12/2025	NON-COMPETING CONTINUATION	$697,735
2025	2024	THE MEDICAL UNIVERSITY OF SOUTH CAROLINA	179 ASHLEY AVE	CHARLESTON	SC	29425	CHARLESTON	USA	Drug Use and Addiction Research Programs	000	1	11/7/2024	NEW	$0
														Subtotal = $697,735

Issue Date FY: 2024 ( Subtotal = $705,077 )
2024	2024	THE MEDICAL UNIVERSITY OF SOUTH CAROLINA	179 ASHLEY AVE	CHARLESTON	SC	29425	CHARLESTON	USA	Drug Use and Addiction Research Programs	000	1	9/18/2024	NEW	$705,077
														Subtotal = $705,077

Grand Total All Awards = $1,402,812

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Impacts of drug abuse-mediated inflammatory perturbations on affinity maturation of anti-CD4 autoantibodies and poor immune reconstitution from ART in HIV

Award Number: R01DA059854

ORGANIZATION: NATIONAL INSTITUTE ON DRUG ABUSE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 09/30/2024

PERIOD OF PERFORMANCE END DATE: 05/31/2029

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