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

NCT05223114 | Completed DMC

• 2 other identifiers: MHREC2152TMA2020CDF-3194
• Study Type: observational
• Target: 160
• Locations: 1 country
• Sites: 1

Brief 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

Keywords

airway microbiome; COPD; HIV

Outcome Measures

Primary Outcomes (3)

• Airway microbial profiling using meta-genomics analysis

  16S sequencing and metagenomics analysis to determine airway bacterial communities

  Month 12-18

• Airway pro-inflammatory and pro-fibrotic gene expression profiling

  RNA sequencing and analysis to determine gene expression profiles

  Month 12-18

• Airway immune cellular profiling

  Airway immune cellular profiling using mass flow time of flight analysis

  Month 12-18

Secondary Outcomes (1)

• Role of Out Membrane Vesicles (OMVs) in mediating microbiome effect on airway immune responses

  Month 12-18

Study Arms (4)

HIV+COPD+

40 male and female adults \> 35 years with COPD and HIV

Other: Not applicable (N/A)

HIV+COPD-

40 male and female adults \> 35 years with HIV but no COPD

Other: Not applicable (N/A)

HIV-COPD+

40 male and female adults \> 35 years with COPD not HIV

Other: Not applicable (N/A)

HIV-COPD-

40 male and female adults \> 35 years with no COPD and no HIV

Other: Not applicable (N/A)

Interventions

Not applicable (N/A) OTHER

Not applicable to this study

HIV+COPD+; HIV+COPD-; HIV-COPD+; HIV-COPD-

Eligibility Criteria

• Age: 35 Years - 100 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

HIV-infected target population: 80 HIV-infected individuals ≥35 years attending the ART clinic at Nakaseke General Hospital screened for COPD following ERS/ATS guidelines. HIV-negative target population: 80 HIV-negative individuals ≥35 years attending the pulmonary clinic at Nakaseke General Hospital screened for COPD following ERS/ATS guidelines. 40 stable COPD participants and 40 participants with no COPD exacerbations.

You may qualify if:

• We will consider samples from Male and female HIV-seropositive and negative individuals ≥35 years who have been screened for COPD as per standard guidelines (European Respiratory Society, ERS, and American Thoracic Society, ATS) using the modified Burden of lung diseases (BOLD) questionnaire and spirometry.

You may not qualify if:

• We will exclude samples from subjects with asthma, significant chronic respiratory disease other than COPD or unable to give informed consent.

Sponsors & Collaborators

• Makerere University: lead
• Charite University, Berlin, Germany: collaborator

Study Sites (1)

Makerere University Lung Institute

Kampala, 256, Uganda

Location

Related Publications (16)

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Related Links

• Organization, W.H., Global status report on noncommunicable diseases 2014. 2014: World Health Organization.
• Organization, W.H., Fact sheet: HIV treatment and care: what's new in HIV treatment. 2015, World Health Organization.

Biospecimen

Retention: SAMPLES WITH DNA

Induced sputum samples

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive; HIV Infections; Respiration Disorders

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Study Officials

• Alex Kayongo, MD

  Makerere University Lung Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 23, 2022
• First Posted: February 3, 2022
• Study Start: April 1, 2022
• Primary Completion: January 31, 2023
• Study Completion: January 31, 2023
• Last Updated: June 13, 2024

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ANALYTIC CODE
• Time Frame: The PI will also make copies of meta data available to co-investigators, students, and others by request within 45 days from receipt of the request unless a longer period is necessary for protection of intellectual property after ethical and institutional clearance. Data will, in principle, be available for access and sharing not later than two years after the acquisition of the data. Key data relevant to the discovery will be preserved until all issues of intellectual property are resolved. Dissemination of data shall be consistent with decisions regarding the management of intellectual property pertaining to the project
• Access Criteria: To be determined at a later time

Locations

UG (1)