# Effect of obesity on HIV pathogenesis, antiretroviral therapy, and metabolic comorbidities

> **NIH NIH R01** · OREGON HEALTH & SCIENCE UNIVERSITY · 2020 · $827,788

## Abstract

PROJECT SUMMARY
The advent of effective antiretroviral therapy (ART) has enabled millions of HIV-infected patients to achieve
long-term remission and survival to middle and old age. This increased survival has resulted in development of
a variety of comorbidities linked to HIV and/or ART, including metabolic disease, AIDS-defining cancers, and
neurocognitive disorders. With respect to metabolic disease in particular, the lipodystrophy associated with
early ART regimes has been replaced by an increased incidence of weight gain and altered adipose tissue
function as well as increased risk for type-2 diabetes in patients on newer ART formulations. Proposed
mechanisms include HIV-induced disruption of gut integrity and translocation of microbial components that can
affect tissue targets such as visceral (particularly omental) adipose tissue to generate a state of chronic
systemic inflammation that is a well-documented cause of metabolic dysfunction. Another major issue affecting
the large population of people living with AIDS is the global epidemic of obesity and diabetes that also affects
people prior to their AIDS diagnosis and initiation of ART. Thus, obesity and prediabetes are increasingly a
pre-existing condition in people living with AIDS, and is the basis for our overall hypothesis that pre-existing
obesity/metabolic disease regulates HIV infection parameters and response to ART and exacerbates adverse
metabolic effects through additive or synergistic effects on systemic inflammation. The in-depth investigation of
the mechanisms that link pre-existing metabolic disease with metabolic comorbidities of HIV and ART requires
preclinical models that enable studies not feasible in human populations. Simian immunodeficiency virus
(SIV)/SHIV-infected nonhuman primates (NHP; rhesus macaques) are the primary preclinical model for study
of HIV acquisition, effects of ART, and vaccine development. NHPs are also the ideal experimental system for
the investigation of pre-existing obesity as it exhibits an obesogenic response to a western-style diet that
mirrors human consumption patterns and is thus an inherently translational model for human diet-induced
obesity and metabolic dysfunction. We propose to merge these two unique NHP models to mimic the state of
affairs in the human population and to address our hypothesis through pursuit of the following specific aims.
Specific aim 1. Determine viral and immunological parameters in lean and obese subjects during SIV challenge
and subsequent ART.
Specific aim 2. Perform comprehensive systemic metabolic profiling in lean and obese subjects during SIV
challenge and subsequent ART.
Specific aim 3. Determine tissue-specific differences in SIV-infected lean and obese subjects before and during
ART.

## Key facts

- **NIH application ID:** 10015274
- **Project number:** 5R01DK122843-02
- **Recipient organization:** OREGON HEALTH & SCIENCE UNIVERSITY
- **Principal Investigator:** Paul Kievit
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $827,788
- **Award type:** 5
- **Project period:** 2019-09-10 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10015274

## Citation

> US National Institutes of Health, RePORTER application 10015274, Effect of obesity on HIV pathogenesis, antiretroviral therapy, and metabolic comorbidities (5R01DK122843-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10015274. Licensed CC0.

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