# Investigate the mechanism of autoreactive B cell-mediated immunological failure despite virologic suppression in HIV-infected individuals on antiretroviral therapy

> **NIH VA I01** · RALPH H JOHNSON VA MEDICAL CENTER · 2022 · —

## Abstract

In HIV infection, circulating CD4+ T cell counts predict disease progression. Even under long-term suppressive
antiretroviral therapy (ART), up to 25% of virologically suppressed people living with HIV (PLWH) fail to restore
CD4+ T cell counts to the levels similar to those in healthy controls, and increased morbidity and mortality have
been demonstrated in these immune non-responders. We were the first group to report that anti-CD4 IgGs
mediate CD4+ T cell death and play a role in poor immune recovery under ART. While the pathogenesis is likely
multifactorial, such as thymic and lymphatic fibrosis, systemic immune activation, and inflammation, our
proposed pathologic anti-CD4 IgG-mediated CD4+ T cell depletion provides a unique mechanism for targeting
CD4+ T cells specifically. In the current study, we will investigate the molecular mechanisms of pathologic anti-
CD4 IgGs and anti-CD4 autoreactive B cells from immune non-responders and identify the therapeutic targets
to prevent anti-CD4 IgG-mediated pathogenesis together with traditional ART to increase immune recovery and
reduce complications, morbidity and mortality in HIV+ Veterans and non-Veterans.
AIM 1. Determine the pathologic activities of anti-CD4 IgGs on CD4+ T cell activation and function and HIV
latency through the CD4 receptor signaling pathway in HIV+ immune non-responders.
AIM 2. Determine the B cell receptor characteristics and gene expression landscape of anti-CD4 autoantibody-
producing B cells from HIV+ immune non-responders.
AIM 3. Determine the biochemical properties and shared antigen binding epitopes of pathologic anti-CD4
monoclonal IgGs in HIV+ immune non-responders.
This line of investigation possesses great therapeutic potential for Veteran and non-Veteran HIV-positive
individuals presenting with poor CD4+ T cell recovery, a population with particularly high risk for morbidity and
mortality and thus an area of public health importance.

## Key facts

- **NIH application ID:** 10368232
- **Project number:** 1I01CX002422-01
- **Recipient organization:** RALPH H JOHNSON VA MEDICAL CENTER
- **Principal Investigator:** Wei Jiang
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2022
- **Award amount:** —
- **Award type:** 1
- **Project period:** 2022-03-01 → 2026-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10368232

## Citation

> US National Institutes of Health, RePORTER application 10368232, Investigate the mechanism of autoreactive B cell-mediated immunological failure despite virologic suppression in HIV-infected individuals on antiretroviral therapy (1I01CX002422-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10368232. Licensed CC0.

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