# New Strategy to Improve Gastrointestinal Health in SIV/HIV

> **NIH NIH R01** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2020 · $776,963

## Abstract

The gastrointestinal (GI) tract is the primary site of HIV replication and CD4+ T cell depletion. HIV induces
major alterations at the mucosal sites, which impact their barrier function, permitting transfer of microbial
products from the intestinal lumen into the surrounding tissues and into the general circulation. This microbial
translocation is a key driver of the chronic immune activation and inflammation (IA/INFL) that are responsible
for HIV disease progression. IA/INFL have a tremendous impact on the outcome of HIV infection, and persist
even in subjects on antiretroviral therapy (ART), preventing a proper recovery of the CD4+ T cells and being
responsible for comorbidities and accelerated aging. Control of chronic IA/INFL is thus one of the major goals
both for prevention of HIV-associated comorbidities and for cure strategies. However, even though the impact
on the GI tract mucosa appears to be central to HIV pathogenesis, approaches aimed at maintaining or
repairing the mucosal barrier are lacking. One of the reasons is that mucosal irritations represented by the
continuous transit of food and by digestive secretions are difficult to counterbalance and therefore the lesions
persist virtually indefinitely. Our hypothesis is that interventions aimed at repairing the intestinal mucosal
damage will be effective in controlling chronic IA/INFL and preventing disease progression,
irrespective of the levels of viral replication. We will test three working hypothesis in three different sets of
experiments: (i) a therapeutic intervention promoting intestinal health in acutely SIV-infected RMs will lead to a
phenotype of viremic controllers of IA/INFL and delayed disease progression; (ii) a therapeutic intervention
promoting intestinal healing in acutely SIV-infected RMs on early ART (modeling current guidelines
recommending early initiation of ART) will result in a complete control of IA/INFL and in complete immune
restoration at the mucosal sites; and (iii) a therapeutic intervention promoting intestinal healing in chronically
SIV-infected RMs on prolonged ART (illustrative of the majority of the HIV infected individuals) will result in a
complete control of IA/INFL and an improved immune restoration at the mucosal sites. For intestinal healing,
we will use an FDA-approved drug (Octreotide, OCT), which (i) reduces intestinal secretions; (ii)
reduces/normalizes intestinal peristalsis; (iii) decreases the release of the vasoactive intestinal peptide (VIP),
thus inducing descending intestinal relaxation; (iv) reduces GI bleeding. Altogether, these effects have the
potential to facilitate intestinal healing. In mice with colitis, somatostatin reduced inflammation and promoted
repairs of the tight junctions, confirming the strong scientific premises of this application. Our approach will
directly probe the utility of promoting intestinal healing in limiting the deleterious consequences of acute and
chronic HIV infection. If successful, our study may ...

## Key facts

- **NIH application ID:** 9954047
- **Project number:** 5R01DK119936-03
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** CRISTIAN APETREI
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $776,963
- **Award type:** 5
- **Project period:** 2018-09-04 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9954047

## Citation

> US National Institutes of Health, RePORTER application 9954047, New Strategy to Improve Gastrointestinal Health in SIV/HIV (5R01DK119936-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9954047. Licensed CC0.

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