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Airway Microbiome and Th17-mediated Inflammation in COPD Among HIV-infected Individuals in a Rural Ugandan Cohort

NCT05223114 · Status: COMPLETED · Type: OBSERVATIONAL · Enrollment: 160

Last updated 2024-06-13

No results posted yet for this study

Summary

Rationale: COPD is increasing in prevalence among people living with HIV/AIDS (PLWHA) as widespread use of ART has increased longevity in this population. In rural Ugandan ART clinics, we report COPD prevalence of 6.22%. Currently, it's not fully known what drives chronic lung inflammation in PLWHA population despite being virologically suppressed on ART. There is need to explore factors driving chronic airway inflammation among PLWHA. Airway microbiome has been implicated in the pathogenesis of COPD. Preliminary analysis from our study revealed that, specific microbes were significantly enriched in PLWHA with COPD with more lung bacteria impacted by HIV than COPD. These findings suggest that HIV-associated changes in unique airway microbial genera may be driving COPD among PLWHA in our cohort. Currently, we don't know how such genera drive chronic airway inflammation.

Study objectives: In this study, we will: (1) establish a relationship between airway microbiome and Th17/Treg cellular phenotypes among HIV-infected individuals with COPD; (2) investigate bacterial-mediated Th17 upregulation of pro-inflammatory and pro-fibrotic genes among HIV individuals with COPD and (3) explore the role of bacterial outer membrane vesicles (OMVs) in mediating microbiome driven Th17 immune responses among HIV individuals.

Methods: We will conduct a 2-year case-controlled study, leveraging on the established lung microbiome cohort in rural Nakaseke district of Uganda. We will recruit 80 HIV-infected individuals ≥35 years attending the ART clinic at Nakaseke General Hospital screened for COPD as well as 80 HIV-negative controls ≥35 years attending the pulmonary clinic at Nakaseke General Hospital screened for COPD. In both cases and controls, we will consider 40 stable COPD participants and 40 participants with no COPD. Recruited participants will undergo sputum induction protocol at our newly established negative pressure sputum induction facility at Nakaseke General Hospital following established standard operating procedures. Using induced sputum samples, we will (i) perform 16S sequencing and metagenomics analysis to determine airway bacterial communities, (ii) RNA sequencing and analysis to determine gene expression profiles, mass flow cytometry and analysis to profile immune cells in induced sputum of study participants as well as (iv) ELISA tests to compare OMV levels between participants.

Conditions

  • COPD
  • HIV Infections
  • Respiratory Disease

Interventions

OTHER

Not applicable (N/A)

Not applicable to this study

Sponsors & Collaborators

  • Charite University, Berlin, Germany

    collaborator OTHER

  • Makerere University

    lead OTHER

Principal Investigators

  • Alex Kayongo, MD · Makerere University Lung Institute

Eligibility

Min Age
35 Years
Max Age
100 Years
Sex
ALL
Healthy Volunteers
Yes

Timeline & Regulatory

Start
2022-04-01
Primary Completion
2023-01-31
Completion
2023-01-31

Countries

  • Uganda

Study Locations

More Related Trials

Entities

Diseases

Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT05223114 on ClinicalTrials.gov