# Targeting Non Viral Markers of HIV Persistence

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2021 · $677,623

## Abstract

PROJECT SUMMARY/ABSTRACT
Despite the ability of combination antiretroviral therapy (ART) to reduce disease-related morbidity and mortality
in HIV-1 infection, viral reservoirs persist. Identification of non-viral markers associated with HIV-1 infection that
can be used as a therapeutic or diagnostic target is a top research priority. Here, we demonstrate that CD30, a
member of the tumor necrosis factor (TNF) receptor superfamily, is preferentially expressed on the surface of
HIV-infected peripheral blood CD4+ T cells and that and HIV-1 transcriptional activity is co-localized within
blood and gut tissues from participants on suppressive ART. In some individuals, HIV-1 DNA or RNA was
exclusively recovered from cells expressing CD30. In further preliminary studies, ex vivo treatment with
brentuximab vedotin, an FDA approved monoclonal antibody-drug conjugate (ADC) that targets CD30, resulted
in up to a 4 log10 reduction in cell-associated HIV-1 DNA in samples obtained from individuals on ART. Despite
these exciting data, several important questions remain. The stability of expression of CD30 and on latently
infected blood and tissue-derived cells and the tissue burden and phenotypic relationships between CD30+
cells with other immune cell phenotypes is poorly understood. Even if CD30 expression waxes and wanes in
infected cells, continued exposure to CD30 targeted therapies could progressively eliminate much of the
reservoir. More potent reductions in HIV burden would be expected in the setting of concomitant anti-C30
therapy and latency reversal. The timing of this proposal is key as there are novel anti-CD30 therapies, such
as CD16/CD30 bispecific antibodies to elicit antibody-dependent cellular cytotoxicity, in clinical development.
 We hypothesize that CD30 expression is stably expressed on HIV-infected, tissue-resident cells and
will provide a specific therapeutic or immune target for HIV eradication. These tissue-resident cells can exist in
a privileged immune environment and are likely to express markers of T cell activation and immune
checkpoint/exhaustion and share features of TFH cells, an important source of persistent HIV. Results from
prior cancer studies indicate that expression of key retrovrial regulatory proteins may lead to increased surface
CD30 expression. However, latently infected cells may also stably express CD30, as we have observed
several ART-suppressed individuals with a large majority of HIV-1 DNA recovered from CD30+ lymphocytes.
Our aims are to: (1) determine if CD30 is preferentially and stably expressed on HIV-infected peripheral blood
and tissue resident cells in individuals on suppressive ART treated during very early or late infection; (2)
determine if ex vivo administration of brentuximab vedotin in conjunction with latency reversal will lead to
significant reductions in intact cell-associated HIV DNA in PBMC from ART-suppressed individuals, and (3)
determine if CD30 is continuously expressed following developme...

## Key facts

- **NIH application ID:** 10150843
- **Project number:** 5R01AI141003-04
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Timothy Jensen Henrich
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $677,623
- **Award type:** 5
- **Project period:** 2018-05-15 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10150843

## Citation

> US National Institutes of Health, RePORTER application 10150843, Targeting Non Viral Markers of HIV Persistence (5R01AI141003-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10150843. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*