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

> **NIH NIH R01** · MEDICAL UNIVERSITY OF SOUTH CAROLINA · 2024 · $705,077

## Abstract

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.

## Key facts

- **NIH application ID:** 11053664
- **Project number:** 1R01DA059854-01A1
- **Recipient organization:** MEDICAL UNIVERSITY OF SOUTH CAROLINA
- **Principal Investigator:** Wei Jiang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $705,077
- **Award type:** 1
- **Project period:** 2024-09-30 → 2029-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11053664

## Citation

> US National Institutes of Health, RePORTER application 11053664, Impacts of drug abuse-mediated inflammatory perturbations on affinity maturation of anti-CD4 autoantibodies and poor immune reconstitution from ART in HIV (1R01DA059854-01A1). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/11053664. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*