# Molecular Imaging of persistent HIV: CD30

> **NIH NIH R21** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2022 · $282,625

## Abstract

PROJECT SUMMARY: A major hurdle to HIV eradication is the presence of infected cells that persist
despite suppressive antiretroviral therapy (ART). HIV largely resides outside of the peripheral circulation,
and thus, numerous anatomical and lymphoid compartments that have the capacity to harbor HIV are
inaccessible to routine sampling. As a result, there is a limited understanding of the tissue burden of HIV
and the anatomical distribution of HIV transcriptional and translational activity. Novel, non-invasive, in vivo
methods, such as positron emission tomography (PET)-based imaging approaches may provide a means
to visualize the reservoir. A PET-based imaging approach using a radiolabeled SIV anti-gp120 monoclonal
antibody (mAb) has been applied to assess active infection in macaques, but similar approaches in
humans have not been reported. However, the implementation of HIV envelope protein specific mAbs is
likely to be challenging due to low expression of HIV proteins in the setting of suppressive ART. An
alternative approach is to develop and implement tracers for non-viral biomarkers of HIV infected cells.
CD30 is a member of the TNF receptor superfamily that is upregulated on various tumor cells (e.g. Hodgkin
lymphoma) but not expressed on a vast majority of healthy cells. We recently demonstrated that HIV RNA
is highly enriched in CD30+CD4+ T cells on suppressive ART, and targeting CD30 using the FDA approved
cytotoxic antibody-drug conjugate (ADC) brentuximab-vedotin (BV) in vivo and ex vivo leads to reduced
HIV RNA and DNA levels in some individuals. Importantly, CD30 mRNA expression in tissues from
antiretroviral treated participants is found exclusively in HIV RNA+ cells. Because of the lack of expression
on uninfected cells, CD30 is an enticing non-viral marker of transcriptionally active HIV-infected cells that
persist despite suppressive ART. Therefore, we propose to: (1) Synthesize 89Zr-DFO-BV, (2) Collect IND
enabling in vitro and in vivo data including estimate whole-body dosimetry in mice using µPET/CT, (3)
Develop an efficient immunoreactivity assay to support clinical translation, (4) Validate and document the
current Good Manufacturing Practice (cGMP) production of 89Zr-DFO-BV and (5) Conduct first-in-human
PET/MR imaging of CD30 using 89Zr-DFO-BV in viremic, subjects under ART and uninfected controls to
determine pharmacokinetics, dosimetry, proof of concept and safety. We hypothesize that radiolabeled BV
will have activity against CD30 and have favorable dosimetry and pharmacokinetics for human use.
Ultimately, PET/MR imaging of CD30 expressing CD4+ T cells has the potential to provide tissue-wide
anatomical distribution of HIV transcriptionally active cells on ART. Our group has an established pre-
clinical and clinical PET-MR imaging infrastructure and have three human studies involving imaging HIV
persistence currently in process. As a result, this pilot study is feasible and has the capacity to provide a
rigorous founda...

## Key facts

- **NIH application ID:** 10328272
- **Project number:** 5R21AI152936-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Henry F. VanBrocklin
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $282,625
- **Award type:** 5
- **Project period:** 2021-01-12 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10328272

## Citation

> US National Institutes of Health, RePORTER application 10328272, Molecular Imaging of persistent HIV: CD30 (5R21AI152936-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10328272. Licensed CC0.

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