# Intersection of Periodontitis with HIV-Antiretroviral Therapy-Induced Immune Reconstitution Bone Loss, on Alveolar Bone and Tooth Loss, in People Living with HIV

> **NIH NIH R01** · EMORY UNIVERSITY · 2024 · $579,130

## Abstract

PROJECT ABSTRACT
This work is anchored on the findings by our group, and others, showing that prior to treatment, the HIV virus
inflicts bone mineral density (BMD) loss in People living with HIV (PLH) due to multifactorial mechanisms.
Furthermore, Antiretroviral therapy (ART) inflicts additional aggressive, but acute, bone loss within a defined
window (~6 months) following ART initiation. Although some first line ART drugs cause mild bone loss due to
direct effects, the aggressive bone loss characteristic of most highly immunosuppressed PLH, is an indirect effect
of adaptive immune system reconstitution and reactivation, driven in large measure through CD4 T cell activation
which is supported by microbial factors. Because this intense, but acute, BMD loss is driven by inflammatory
events related to immune regeneration, even newer ART drugs cause severe bone loss in severely
immunocompromised patients. Importantly, although we and others have documented this immune
reconstitution bone loss (IRBL) in the long bones and spine, it may not be limited to these compartments and
new preliminary data using our mouse model of IRBL, suggest that the alveolar bone of the jaw anchoring the
teeth, is also severely degraded. This is an important finding given that our extended group has reported that
periodontal infection (periodontitis) is 3-fold higher in PLH. Periodontitis is a chronic inflammatory disease, in
which bacteria such as the periodontal pathogen P. gingivalis, overrun the oral compartment, a likely
consequence of impaired immune surveillance due to HIV-induced immunodeficiency. Like IRBL, periodontitis
also causes loss of the alveolar bone anchoring the teeth, leading to tooth loosening and eventual loss.
Periodontal infection and tooth loss in people is a cause of morbidity, pain, and self-image issues, leading to a
decline in quality of life. We hypothesize that ART-induced IRBL, drives significant alveolar lone loss in PLH, that
exacerbates, or is exacerbated by, HIV-induced periodontal infection, leading to poor oral health that culminates
in tooth loosening and eventual tooth loss. In this application, we propose to study alveolar IRBL and the
intersection of IRBL with periodontitis in a clinical study in PLH (Specific Aim 1) and in a complementary
mechanistic basic science study (Specific Aim 2) using animal models of IRBL and periodontal infection. Findings
from this work will contribute to efforts aimed at identifying PLH at risk of poor oral health leading to tooth loss.
The outcomes will provide strong rationale for exploring targeted prophylaxis including antibiotics and anti-
resorptive drugs to protect the alveolar bone and the teeth from ART-associated IRBL.

## Key facts

- **NIH application ID:** 10924765
- **Project number:** 1R01DE033635-01A1
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** KEHINDE ADESOLA UMEIZUDIKE
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $579,130
- **Award type:** 1
- **Project period:** 2024-08-01 → 2029-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10924765

## Citation

> US National Institutes of Health, RePORTER application 10924765, Intersection of Periodontitis with HIV-Antiretroviral Therapy-Induced Immune Reconstitution Bone Loss, on Alveolar Bone and Tooth Loss, in People Living with HIV (1R01DE033635-01A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10924765. Licensed CC0.

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