# On the pathogenic role of anti-CD4 antibody in poor CD4+ T cell recovery after antiretroviral therapy in HIV disease

> **NIH NIH R01** · MEDICAL UNIVERSITY OF SOUTH CAROLINA · 2021 · $191,828

## Abstract

Human immunodeficiency virus (HIV) disease has been significantly controlled following the introduction of
antiretroviral therapy (ART) [1]. This treatment dramatically improves immune function, suppresses HIV viral
replication, and decreases morbidity and mortality [1, 2]. However, up to 25% of virologically suppressed
individuals (~111,000 people in USA) fail to restore their CD4+ T cells to counts > 350 cells/µL, even after long-
term ART treatment and viral suppression [3], and increased morbidity and mortality have been observed in
these patients [4-7]. Thymic fibrosis has been suggested a mechanism, and low nadir CD4+ T cell counts and
T cell activation have been shown to associate with incomplete immune restoration after ART treatment [8-11],
but mechanisms for immune non-response remain largely unknown. To better understand mechanisms of
incomplete immune restoration, we performed a preliminary human study in 12 healthy controls, 17
immunologic responders (IRs) (aviremic and ART treated > 3 years, and CD4+ T cell counts > 500 cells/µL)
and 11 immunologic non-responders (INRs) (aviremic and ART treated > 3 years, and CD4+ T cell counts <
350 cells/µL) [8]. Elevated plasma levels of anti-CD4 IgGs were found in patients compared to controls and
correlated with blunted CD4+ T cell recovery. Furthermore, purified anti-CD4 IgGs from plasma of aviremic
long-term ART-treated subjects with CD4+ T cell counts below 350 cells/µl, defined as “immunologic non-
responders”, induced antibody-dependent NK cell-mediated cytotoxicity against CD4+ T cells. We hypothesize
that heightened level of anti-CD4 Ab contributes to the pathogenesis of CD4+ T cell losses in HIV infection. If
our hypothesis is correct, a therapeutic strategy that targeting autoreactive B cells or anti-CD4 Abs could
potentially optimize ART treatment to improve CD4+ T cell recovery and reduce mortality and morbidity in
treated HIV-infected patients. This study will also provide important information in HIV vaccine design.

## Key facts

- **NIH application ID:** 10141185
- **Project number:** 5R01AI128864-05
- **Recipient organization:** MEDICAL UNIVERSITY OF SOUTH CAROLINA
- **Principal Investigator:** Wei Jiang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $191,828
- **Award type:** 5
- **Project period:** 2017-05-19 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10141185

## Citation

> US National Institutes of Health, RePORTER application 10141185, On the pathogenic role of anti-CD4 antibody in poor CD4+ T cell recovery after antiretroviral therapy in HIV disease (5R01AI128864-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10141185. Licensed CC0.

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