# SIV Pathogenesis in African Green Monkeys and Pigtailed Macaques

> **NIH NIH R01** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2020 · $779,620

## Abstract

This is the resubmission of the competitive renewal of our RO1 that generated >63 publications over a 12-year
funding period. Our goal is to assess the impact of dietary factors on chronic inflammation (INFL) profiles
associated with cardiovascular disease (CVD) in treated and untreated SIV infections. As reported in other
clinical conditions, diet plays a key role in modulating gut INFL, epithelial integrity and microbial translocation
through shifts in microbiota metabolites, which may also induce excessive cell proliferation and activation or a
skewed cell differentiation, resulting in a reduction of the immune cell subsets critical for gut health. Diet-induced
changes in the host cellular fat and sugar metabolism may enhance SIV/HIV replication, reduce immune cell
responses and promote cell senescence. Certain diets thus have the potential to enhance gut dysfunction during
SIV/HIV infection. In addition to the impact on the gut, the diet-induced changes in microbiota may trigger
changes in the adipose tissue that promote systemic INFL and induce liver damage that may associate abnormal
clearance of microbial products, antiretroviral (ARV) metabolism and coagulation factor synthesis. Our
hypothesis is therefore that, in the context of HIV/SIV, the dietmicrobiotametabolite axis has a critical impact
on IA/INFL, response to ART and development of CVD. Long-term, perfectly controlled diet studies are very
difficult to carry out in HIV+ infected subjects and can be confounded by numerous other factors (i.e., ART, age,
alcohol, drugs, smoking, lack of physical activity) that may affect the same metabolic pathways. Our preliminary
data show that administration of a high fat diet to SIV-infected NHPs induced alterations in the gut microbiota,
MT, nonalcoholic fatty liver and increases in systemic IA/INFL, which altogether resulted in a significantly
decreased survival. Based on these preliminary data and the rationales above, and as a logical continuation of
the research from the previous funding periods, we designed this project, aimed at assessing the impact of major
dietary components on the natural history of SIV infection and the development of SIV-related CVD in ART-naïve
NHPs and chronically infected NHPs on ART. In an NHP model developed in our lab, that faithfully reproduces
the CVD described in HIV+ subjects, we will perform controlled studies to test the long term effects of multiple
diets prior and after SIV infection, on or off ART. These experiments will establish the pathways impacted by
each dietary component and cannot be performed in HIV+ subjects due to the difficulty to maintain strict diets,
the risks associated with certain diets that can produce harm, and to the impossibility to perform extensive
invasive sampling. Our goal is to develop a permanent drug-free, no risk adjuvant therapy for HIV+ subjects, to
reduce residual INFL, improve immune function and decrease the CV comorbidities. If successful, these highly
translationa...

## Key facts

- **NIH application ID:** 9886276
- **Project number:** 5R01HL117715-15
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Ivona Vasile Pandrea
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $779,620
- **Award type:** 5
- **Project period:** 2005-02-01 → 2022-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9886276

## Citation

> US National Institutes of Health, RePORTER application 9886276, SIV Pathogenesis in African Green Monkeys and Pigtailed Macaques (5R01HL117715-15). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9886276. Licensed CC0.

---

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