# Determining the component causes of systemic immune activation that moderate HIV acquisition and establishment of the latent viral reservoir

> **NIH NIH K23** · UNIVERSITY OF WASHINGTON · 2021 · $142,285

## Abstract

ABSTRACT
There are 2 million new HIV infections in the world each year. Acquisition of HIV is only partially
explained by exposure, behavior, and concurrent sexually transmitted infections. There is
growing evidence that both local and systemic immune activation may make target cells more
susceptible to HIV. Studies that have noted associations with immune activation and HIV
acquisition have not been equipped to identify specific disease states that accompany these at-
risk profiles. Because the latent HIV reservoir is established within days of infection, and
susceptibility of HIV target cells is modified by immune activation, the inflammatory state at the
time of HIV acquisition may modulate the quantity of cells at risk, and therefore the size of the
latent HIV reservoir. We will identify inflammatory profiles that modulate risk of HIV acquisition
and size of the latent viral reservoir among high-risk men who have sex with men (MSM) in an
established cohort in Lima, Peru. We will attempt to determine the component causes of
immune activation, including persistent and transient viral infections, alcohol and substance use,
and sexual exposure that contribute to this high-risk immune activation. In this Peruvian cohort,
HIV-negative MSM were followed with monthly visits, questionnaires, and banked blood
samples. MSM who acquired HIV were enrolled in a follow-up study and received antiretroviral
therapy (ART) immediately or after 24 weeks, and will continue to be followed for the next four
years. In Aim 1, we will use a nested case-control design to compare cytokine profiles and a
novel viral serologic assay (VirScan) from matching time-points in MSM who did and did not
acquire HIV to evaluate predictors of HIV acquisition. In Aim 2, we will evaluate immune
activation and viral infections present immediately prior to HIV acquisition as predictors for size
of the latent viral reservoir in MSM who acquired HIV. We will build statistical models to
describe the role of viruses and other component causes of immune activation on HIV
acquisition and reservoir size, respectively. Innovations in our study include the addition of
cutting edge technology to evaluate immune responses to known viral infections (VirScan) to
multidimensional cohort data to better identify human and cellular susceptibility to HIV infection,
and the ability to connect causes of inflammation and markers of immune activation within a
very narrow exposure period prior to HIV acquisition. We expect that the results of this study will
improve our understanding of the pathophysiology of HIV susceptibility and allow further work
towards biomedical interventions to prevent HIV infection and modulate the latent HIV reservoir.

## Key facts

- **NIH application ID:** 10086370
- **Project number:** 5K23AI129659-05
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** Rachel Ann Bender Ignacio
- **Activity code:** K23 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $142,285
- **Award type:** 5
- **Project period:** 2017-01-05 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10086370

## Citation

> US National Institutes of Health, RePORTER application 10086370, Determining the component causes of systemic immune activation that moderate HIV acquisition and establishment of the latent viral reservoir (5K23AI129659-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10086370. Licensed CC0.

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