# Evaluating the Relationship Between Age and HIV-1 Persistence

> **NIH NIH UM1** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2024 · $375,973

## Abstract

Abstract
Evaluating curative interventions in older people on antiretroviral therapy (ART) is challenging due to the complex
interplay between HIV infection, aging, and age-related comorbidities. We have recently shown in 14 people with
HIV (PWH) receiving long-term ART that there are three patterns of intact proviral DNA decay: 1) a biphasic
decline with markedly slower second phase decline; 2) an initial decline followed by a zero-slope plateau; and
3) an initial decline followed by later increases in intact proviral DNA. In this study, the two participants who had
an increase in intact proviral DNA were females >60 years old and had been on ART for up to 20 years. This
important result raises the question whether age is associated with a slowing decay in intact proviral
DNA among PWH on long-term ART. Accordingly, we will extend these preliminary observations to a large
longitudinal cohort (ACTG A5321) of men and women with a median duration of ART of 14 years (IQR 12 – 17)
(range 5-24 years) and archived blood samples every six months. In addition, cellular senescence is also a factor
that could affect HIV persistence as people age. Senescent cells are in a state of cell-cycle arrest and acquire
the senescence associated secretory phenotype (SASP) resulting in an inflammatory state. If this inflammatory
environment created by SASP leads to proliferation of HIV-infected cells, then senescent cells may play a role
in slowing or reversing the decay of intact proviruses. The central hypothesis of this proposal is that markers
of HIV persistence are more likely to slow their decline, or increase, with age on ART, in association with
increasing markers of immune senescence. To address this hypothesis, we will 1) assess the
longitudinal relationship between age/sex and the levels and trajectory of HIV-1 reservoirs on ART, and
2) determine the longitudinal relationships between the levels and trajectory of HIV persistence markers
and SASP markers. The duration of ART in this ACTG A5321 cohort is much longer than in many other studies
as participants have been in continuous follow-up since initiation of ART and have well-documented virologic
suppression for approximately 20 years with detailed clinical, laboratory, reservoir data and additional blood
samples from immediately pre-ART through the present day. We will evaluate 100 A5321 participants over
multiple timepoints for levels of intact proviral DNA, total DNA, residual HIV-1 RNA using the single copy assay
and assess the relationships between levels of these persistence markers and age/sex. In a subset of 25
participants, we will perform bulk integration site analysis to determine the clonality of cells carrying proviruses
as a function of age. We will also measure a panel of SASP markers using a multiplex platform using samples
from the 100 participants in Aim 1 to assess whether the measures of HIV persistence in Aim 1 are associated
with the markers of senescence.

## Key facts

- **NIH application ID:** 10846033
- **Project number:** 3UM1AI068636-18S2
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Judith S. Currier
- **Activity code:** UM1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $375,973
- **Award type:** 3
- **Project period:** 2006-06-29 → 2027-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10846033

## Citation

> US National Institutes of Health, RePORTER application 10846033, Evaluating the Relationship Between Age and HIV-1 Persistence (3UM1AI068636-18S2). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10846033. Licensed CC0.

---

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