# Impact of Methamphetamine Use on the HIV Nucleome in Individuals on Antiretroviral Therapy

> **NIH NIH R61** · UNIVERSITY OF WASHINGTON · 2020 · $1,014,569

## Abstract

PROJECT SUMMARY/ABSTRACT
A major challenge in ending the HIV pandemic is the persistence of the latent HIV reservoir that can lead to
viremia, disease progression and transmission to new hosts after discontinuation of antiretroviral therapy
(ART). Efficient treatment regimens that successfully eliminate cell populations carrying intact proviruses are
not available due to the incomplete understanding of the cellular mechanisms that allow the virus to remain
quiescent within the host genome. A compounding risk factor in HIV pathology is substance use disorder
(SUD) known to contribute to decreased adherence to and delay of viral decay due to ART, and accelerated
progression to AIDS. We hypothesize that persistence of HIV reservoirs is encoded in the proviral location
within the 3D architecture of the host genome (nucleome), and influenced by SUD-induced changes in
epigenetic structures.
During the exploratory high-risk R61 phase of this project, we will first identify SUD-related differences in HIV
integration site patterns, the epigenome and the nucleome of CD4+ T lymphocytes derived from patient
cohorts that differ in their exposure to methamphetamine (meth). In the second aim, we will apply advanced
3D nucleome mapping strategies to define the interdependence of nuclear structure, proviral genomic
location, regulatory elements, and transcriptomes in short-term ex vivo cultivated patient-derived cells from
both cohorts. In the third aim, we will use gene-editing techniques to precisely define a role for proviral
integration sites (identified in aims 1 and 2) in cellular gene activity and HIV persistence, including those
related to meth use.
In the R33 phase we propose to assess the impact of targeted provirus integration on nucleome architecture
and transcriptomes to clearly identify genes essential for establishing the ART-resistant HIV reservoir. In
addition, we will pursue a strategy to define chromatin interactions of proviral integrations and host genes in
vivo in human CD4+ T cell populations of HIV-infected individuals.

## Key facts

- **NIH application ID:** 9931193
- **Project number:** 5R61DA047010-03
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** Zhijun Duan
- **Activity code:** R61 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $1,014,569
- **Award type:** 5
- **Project period:** 2018-08-15 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9931193

## Citation

> US National Institutes of Health, RePORTER application 9931193, Impact of Methamphetamine Use on the HIV Nucleome in Individuals on Antiretroviral Therapy (5R61DA047010-03). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9931193. Licensed CC0.

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