Relationship of Inflammation and Pulmonary Function to Fungal Translocation in HIV

NCT05502653 | Recruiting

• 1 other identifier: STUDY22030175
• Study Type: observational
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

The investigator will study the origin of fungal translocation in HIV, its relationship to the mycobiome, and its relationship to lung function and inflammation. Supported by the preliminary data and published studies, this project is based on the premise that circulating BDG derived from microbial translocation stimulates inflammation and worsens lung function in PWH. Chronic obstructive pulmonary disease (COPD) is a significant public health problem with few therapies that modify disease trajectory. COPD is a leading cause of mortality in the United States associated with increased morbidity and healthcare costs. Long-acting bronchodilators and inhaled corticosteroids are mainstays of therapy that control symptoms and reduce acute exacerbation frequency, but do not have a significant impact on mortality or lung function trajectory. The National Heart, Lung, and Blood Institute's COPD National Action Plan focuses on the critical need for research to characterize COPD risk factors and disease mechanisms in order to improve the understanding of causes and progression of disease. The ultimate goal is to provide precision therapy to appropriate patient subgroups to preserve health or arrest disease progression. Microbial organisms in the gut may have a profound effect on lung disease. The role of the gut-lung axis, defined as the cross-talk between gut microbiota and the lungs, in the pathogenesis of chronic respiratory diseases is emerging as an area of interest. Perturbations of gut microbiota characterized by low microbial diversity and changes in microbiota abundance are linked to childhood asthma risk, airflow obstruction in adult asthma, and severe lung dysfunction in cystic fibrosis. Studies in animals show that both a high fiber diet that modulates gut microbiota and an abundance of beneficial bacterial strains attenuate inflammation, emphysema, and COPD development in response to cigarette smoke exposure in murine models. In humans, recent investigations show differences in the gut microbial communities between COPD patients and healthy individuals as well as shifts in the gut microbiome with acute exacerbations of COPD.

Conditions

HIV Infections; Inflammation; COPD

Outcome Measures

Primary Outcomes (6)

• Assess intestinal and lung permeability with the lactulose/mannitol differential sugar absorption test

  measure of BDG levels with the Fungitell assay44 in urine collected after 5 grams of lactulose and 2 grams of mannitol have been ingested

  urine collection over 6 hours after ingestion of sugar solution at baseline

• Assess intestinal and lung permeability with the lactulose/mannitol differential sugar absorption test

  measure of BDG levels with the Fungitell assay44 in urine collected after 5 grams of lactulose and 2 grams of mannitol have been ingested

  urine collection over 6 hours after ingestion of sugar solution at 18 months

• Assess intestinal and lung permeability with the lactulose/mannitol differential sugar absorption test

  measure of BDG levels with the Fungitell assay44 in urine collected after 5 grams of lactulose and 2 grams of mannitol have been ingested

  urine collection over 6 hours after ingestion of sugar solution at 36 months

• BDG levels will be assayed in undiluted plasma samples

  Using the Fungitell Assay (Associates of Cape Cod, East Falmouth, MA)62,63 according to manufacturer's instructions, modified to utilize a lower standard curve, 7.8 -250 pg/mL. The Fungitell Assay is a chromogenic kinetic test that was approved by the Food and Drug Administration in 2003 for the clinical measurement of BDG with \>80 pg/mL is considered a positive test.

  Blood will be collected at baseline after ingestion of 5 grams of lactulose and 2 grams of mannitol.

• BDG levels will be assayed in undiluted plasma samples

  Using the Fungitell Assay (Associates of Cape Cod, East Falmouth, MA)62,63 according to manufacturer's instructions, modified to utilize a lower standard curve, 7.8 -250 pg/mL. The Fungitell Assay is a chromogenic kinetic test that was approved by the Food and Drug Administration in 2003 for the clinical measurement of BDG with \>80 pg/mL is considered a positive test.

  Blood will be collected at 18 months after ingestion of 5 grams of lactulose and 2 grams of mannitol.

• BDG levels will be assayed in undiluted plasma samples

  Using the Fungitell Assay (Associates of Cape Cod, East Falmouth, MA)62,63 according to manufacturer's instructions, modified to utilize a lower standard curve, 7.8 -250 pg/mL. The Fungitell Assay is a chromogenic kinetic test that was approved by the Food and Drug Administration in 2003 for the clinical measurement of BDG with \>80 pg/mL is considered a positive test.

  Blood will be collected at 36 months after ingestion of 5 grams of lactulose and 2 grams of mannitol.

Secondary Outcomes (3)

• Determine if higher circulating BDG levels predict disease progression and systemic immune cell activation in HIV COPD

  baseline

• Determine if higher circulating BDG levels predict disease progression and systemic immune cell activation in HIV COPD

  at 18 months

• Determine if higher circulating BDG levels predict disease progression and systemic immune cell activation in HIV COPD

  at 36 months

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

People living with HIV

You may qualify if:

• Age 18 to 80
• HIV positive
• Virally-suppressed on ART for at least 6 months
• subjects enrolled in Dr. Morris's HLRC Studies STUDY20020151, STUDY19080258, STUDY19060243, STUDY19070181, STUDY19070181, STUDY19050326 OR subjects being seen at the HIV/PACT clinics.

You may not qualify if:

• Contraindication to pulmonary function testing (i.e., abdominal or cataract surgery within 3 months, recent myocardial infarction, etc.).
• individuals with clinical or radiographic evidence of another significant pulmonary diagnosis (e.g. interstitial lung disease, active asthma)
• inflammatory bowel disease
• pregnancy
• use of antibiotics in the prior 2 weeks
• immunomodulators in the prior 6 months
• unable to perform any study procedures.

Sponsors & Collaborators

• University of Pittsburgh: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (1)

University of Pittsburgh

Pittsburgh, Pennsylvania, 15213, United States

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

urine, blood, oral wash, sputum, stool

MeSH Terms

Conditions

HIV Infections; Inflammation; Pulmonary Disease, Chronic Obstructive

Condition Hierarchy (Ancestors)

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; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes

Study Officials

• Alison J Morris, MD

  University of Pittsburgh

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Cathy J Kessinger

CONTACT

412-624-8330; kessingercj@upmc.edu

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: August 3, 2022
• First Posted: August 16, 2022
• Study Start: September 1, 2022
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): August 1, 2027
• Last Updated: September 12, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)