# Reversing HIV-induced B cell dysfunction with bisphosphonates

> **NIH NIH K01** · EMORY UNIVERSITY · 2020 · $118,272

## Abstract

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DESCRIPTION (provided by applicant): Life expectancies for people living with HIV remain lower than for the general population, but thanks to the success of combination antiretroviral therapy (ART), HIV-infected individuals are living longer than ever before. It is estimated that half of the HIV/AIDS population in the US are now 50 years or older. This increased longevity is accompanied by increased prevalence and earlier incidence of non-AIDS age- related comorbidities including renal, hepatic, pulmonary, cardiovascular, neurocognitive, and skeletal disease. The mechanisms underlying these conditions remain poorly understood but inflammation driven by a damaged immune response likely contributes significantly to end organ damage. Ameliorating these comorbidities is increasingly becoming a major challenge in HIV disease management. HIV infection leads to severe impairment of the B cell compartment, which is not completely reversed by ART and manifests as B cell hyperactivity coupled paradoxically with hypo-responsiveness to natural non-HIV infections and vaccinations, due to impaired production of antigen-specific antibodies. While these aspects of B cell dysfunction have been the subject of intense research for the past two decades, emerging evidence now suggests that HIV-induced B cell dysfunction may have far-reaching consequences beyond impaired antibody responses to infections. Bisphosphonates are small-molecule inhibitors of bone resorption clinically approved for the treatment of osteoporotic conditions. Importantly, recent studies in bisphosphonate-treated mice unexpectedly showed increased generalized antigen (Ag)-specific humoral immune responses. Bisphosphonates are widely used in clinical settings and may thus be an attractive agent for mitigating B cell dysfunction, enhancing humoral immune responses, attenuating inflammation and ameliorating end-organ complications in HIV-infected people. We hypothesize that HIV-induced B cell dysfunction is integral to the development of a global pro-inflammatory state that contributes to end-organ impairment in chronic HIV-infection. Moderating and/or reversing this B cell dysfunction may mitigate or prevent organ damage in the aging HIV/AIDS population. To test this hypothesis, we will investigate whether this pro-inflammatory state can be ameliorated by treatment with a potent long acting bisphosphonates, zoledronic acid. (End of Abstract)

## Key facts

- **NIH application ID:** 9850277
- **Project number:** 5K01HL131333-05
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Kehmia Nubonyin Titanji
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $118,272
- **Award type:** 5
- **Project period:** 2016-02-12 → 2021-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9850277

## Citation

> US National Institutes of Health, RePORTER application 9850277, Reversing HIV-induced B cell dysfunction with bisphosphonates (5K01HL131333-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9850277. Licensed CC0.

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