# Harnessing multi-omics to identify host-microbiome interactions driving HIV-associated chronic obstructive pulmonary disease in low and middle income countries.

> **NIH NIH DP1** · DUKE UNIVERSITY · 2024 · $513,006

## Abstract

ABSTRACT
Chronic obstructive pulmonary disease (COPD) affects 300 million people and is the third leading cause of
death globally, with >80% of these deaths occurring in low- and middle-income countries (LMICs). LMICs,
particularly those in sub-Saharan Africa, are also home to over two thirds of the global population of people
with HIV (PWH). HIV increases the risk of COPD and COPD-associated mortality, but the mechanisms
underlying this risk are incompletely understood, which in turn limits our ability to identify PWH at the highest
risk of developing COPD. Elucidating mechanisms that lead to COPD in PWH in LMICs is particularly
important, as an estimated one third of COPD cases in LMICs are not attributable to known COPD risk factors.
Systemic inflammation is associated with disease severity in COPD and impaired lung function in PWH, but it
is unknown if inflammatory pathways affecting lung function in PWH are distinct from those in people without
HIV. Furthermore, most data on inflammation in PWH and impaired lung function were generated by
measuring a limited number of cytokines, which yields an incomplete picture of the inflammatory pathways
involved. Microbial communities in the lung, gut, and oral cavity are also altered in patients with COPD and
data from the US suggest a causal link between the microbiome and COPD among PWH. Host-microbe
interactions likely explain the association between microbiome alterations and COPD in PWH, but these
interactions are not fully understood, particularly in LMIC populations that face the greatest COPD-associated
morbidity and mortality. Using my experience with microbiome analysis and the pulmonary research
infrastructure I built in Botswana, I will incorporate shotgun metagenomic sequencing of multiple microbial
communities (saliva, sputum, stool), host transcriptomics, and untargeted metabolomics to characterize the
effect of host-microbiome interactions on pulmonary function in a longitudinal cohort of adults with and without
HIV in Botswana. I will collect clinical, demographic, and spirometry data from 500 adults with chronic
respiratory symptoms (250 PWH, 250 HIV-uninfected) and will then collect specimens and spirometry every six
months for 24 months in a stratified random sample of 200 adults. Specimens will be shipped to Duke
University for DNA and RNA sequencing and mass-spectrometry based metabolomics in advanced core
facilities. I will use advanced statistical methods that incorporate machine learning to identify unique host
pathways associated with microbiome composition in PWH and COPD and develop and validate a predictive
model to identify PWH and COPD. This proposal will advance our understanding of how host-microbiome
interactions affect inflammation and pulmonary function in PWH, thus addressing a key priority for the National
Heart, Lung, and Blood Institute. Furthermore, this proposal will establish a clinical cohort and robust
biorepository that, coupled with our findings, will supp...

## Key facts

- **NIH application ID:** 10918374
- **Project number:** 1DP1HL174240-01
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Sweta Mahesh Patel
- **Activity code:** DP1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $513,006
- **Award type:** 1
- **Project period:** 2024-09-25 → 2029-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10918374

## Citation

> US National Institutes of Health, RePORTER application 10918374, Harnessing multi-omics to identify host-microbiome interactions driving HIV-associated chronic obstructive pulmonary disease in low and middle income countries. (1DP1HL174240-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10918374. Licensed CC0.

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