# Multidimensional single-cell approach probing HIV-1 integration association with non-AIDS defining cancers (Biospecimens/Biocohort)

> **NIH NIH P30** · UT SOUTHWESTERN MEDICAL CENTER · 2022 · $250,000

## Abstract

PROJECT SUMMARY
 Current treatments for HIV-1 infection include suppressive anti-retroviral therapy (ART), which curtails
active viral replication to nearly undetectable levels. However, ART fails to cure HIV-1 infection because the
virus persists indefinitely in a latent state. While people living with HIV-1 (PLWH) live longer, they are subject to
secondary long-term consequences due to the ART regime itself and the presence of integrated proviruses
throughout the human genome. Whereas ART facilitated a decrease in the incidence of AIDS defining cancers,
an increased incidence of non-AIDS defining cancers (NADC), such as T and B cell lymphomas, has been well
documented in the clinics. Despite previous controversies regarding the role of HIV-1 integration site and
cancer prevalence, the clinical association between HIV-1 integration in defined sites and NADC prevalence
remains largely unexplored. Given these previous findings and gaps in knowledge, the central hypothesis of
this proposal is that HIV-1 integration into or nearby select human genes alters their expression thereby
causing NADC. Specifically, HIV-1 integration might disrupt the normal expression of HIV-1 Associated GEnes
(HAGEs) causing upregulation of proto-oncogenes, downregulation of tumor suppressors and/or altering RNA
splicing patterns, consequently rewiring gene expression programs producing abnormal CD4+ T and B cell
expansion and/or behaviors leading to NADC.
 The major goal of this proposal is to interrogate whether select HIV-1 integration sites are associated with
increased incidence of NADC in PLWH under suppressive therapy and to predict associated biomarkers. To
start accomplishing this goal, we will deploy a multidimensional approach to concurrently profile HIV-1
integration sites and human transcriptomes at the single cell level in a unique cohort available through the
AIDS and Cancer Specimen Resource (ACSR). This will be the first ever approach that can simultaneously
interrogate the relationship between HIV-1 integration sites and human transcriptomes at the single cell level in
participants biospecimens. We already have on hand an impressive molecular and genomic toolset that will be
strategic for accomplishing the Specific Aims of this proposal. These include: 1) To deploy a multidimensional
single cell approach to simultaneously collect HIV-1 integration sites and human transcriptomes in ACSR
participants biospecimens (Aim 1), and 2) to combine the generated datasets to define participants HIV-1
integration-induced biomarkers associated with NADC (Aim 2). Collectively, these studies will reveal viral
integration sites over-represented in PLWH with NADC, link individual viral integration sites to altered human
gene expression potentially explaining the onset of NADC, and categorize biomarkers linked to select HIV-1
integration events for diagnostic and prognostic outcomes. Future studies using this knowledge will functionally
define specific HIV-1 integration ev...

## Key facts

- **NIH application ID:** 10619156
- **Project number:** 3P30CA142543-12S1
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **Principal Investigator:** Carlos L Arteaga
- **Activity code:** P30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $250,000
- **Award type:** 3
- **Project period:** 2010-09-01 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10619156

## Citation

> US National Institutes of Health, RePORTER application 10619156, Multidimensional single-cell approach probing HIV-1 integration association with non-AIDS defining cancers (Biospecimens/Biocohort) (3P30CA142543-12S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10619156. Licensed CC0.

---

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