Immunosuppressive Effects of Smoking and HIV-1 on the Development of Lung Disease

NCT02058719 | Completed

• 1 other identifier: 13-2986
• Study Type: observational
• Target: 210
• Locations: 1 country
• Sites: 1

Brief Summary

This study plans to learn more about pulmonary complications of human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS). Even though antiretroviral therapy (ART) has dramatically decreased the number of opportunistic infections and deaths in HIV infected patients, pulmonary complications (including chronic obstructive pulmonary disease (COPD) development and pneumonias resulting in decreased lung function) of HIV/AIDS continue to be a major cause of morbidity and mortality in this population. The mechanisms underlying the increased risk of COPD and decreased lung function in HIV infected individuals is not well understand and needs to be studied. The investigators hypothesize that the immunoregulatory consequences and immunosuppressive lung milieu secondary to HIV and cigarette smoke combine to increase the risk of lung infection and injury in HIV infected smokers, hastening the development of COPD. The mechanisms will be directly tested using blood and bronchial alveolar lavage (BAL) cells from smokers and nonsmokers with and without HIV infection.

Conditions

HIV; Smoking; COPD

Outcome Measures

Primary Outcomes (2)

• The change in immunoregulatory markers: PD-1 expression and interleukin (IL)-10 production by alveolar macrophages (AMs) from baseline to week 24.

  Evaluate the immunoregulatory change between HIV positive (smokers/non-smokers) and HIV negative (smokers/non-smokers)

  Baseline, Week 24

• PD-1 expression and IL-10 production by AMs at baseline

  Evaluate the association of PD-1 expression and IL-10 production by AMs after long-term antiretroviral therapy (ART) with abnormal lung function and a COPD phenotype between HIV positive (with and without COPD) and HIV negative with COPD.

  Baseline

Study Arms (7)

Cohort A1

HIV positive smokers

Cohort A2

HIV positive non-smokers

Cohort A3

HIV negative smokers

Cohort A4

HIV negative non-smokers

Cohort B1

HIV positive with COPD

Cohort B2

HIV positive without COPD (non-COPD)

Cohort B3

HIV negative with COPD

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

HIV positive (smokers and non-smokers) and negative subjects (smokers and non-smokers) will be recruited. HIV positive (with and without COPD) and HIV negative with COPD will also be recruited. All subjects will be between ages 18 and 70.

You may qualify if:

• Subjects with chronic HIV-1 infection (Cohorts A1 and A2)
• ART naïve or off all ART for \>6 months (Cohorts A1 and A2)
• HIV-1 RNA level \>1,000 copies/ml (Cohorts A1 and A2)
• HIV-1 seronegative with no high-risk exposure in the past 30 days (Cohorts A3 and A4)
• years and older (All Cohort A)
• Active cigarette smoker (Cohorts A1 and A3)
• Age from 30 to 70 years
• Subjects with chronic HIV-1 infection (Cohorts B1 and B2)
• Subjects on stable 3-drug ART regimen with plasma HIV-1 RNA \<50 copies/mL for past 6 months (Cohorts B1 and B2)
• HIV-1 seronegative with no high-risk exposure in the past 30 days (Cohort B3) COPD: forced expiratory volume at one second (FEV1)/forced vital capacity (FVC) \<70% and forced expiratory volume (FEV), 45-100% of predicted (Cohort B1 and B3)
• Non-COPD: FEV/FVC \>70% and an FEV, \>80% of predicted (Cohort B2)

You may not qualify if:

• Pregnancy
• Weight less than 110 pounds (for venipuncture)
• Patient inability to participate in the study and undergo venipuncture and bronchoscopy procedures
• Use of systemic or inhaled corticosteroids in the past 3 months.

Sponsors & Collaborators

• University of Colorado, Denver: lead

Study Sites (1)

University of Colorado Denver

Aurora, Colorado, 80045, United States

Location

Biospecimen

Retention: SAMPLES WITHOUT DNA

Blood and bronchoscopy (BAL) samples will be collected

MeSH Terms

Conditions

Smoking; Pulmonary Disease, Chronic Obstructive

Condition Hierarchy (Ancestors)

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

Study Officials

• Thomas B. Campbell, MD

  University of Colorado, Denver

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 5, 2014
• First Posted: February 10, 2014
• Study Start: March 1, 2014
• Primary Completion: July 1, 2019
• Study Completion: December 1, 2019
• Last Updated: December 18, 2019

Record last verified: 2019-12

Locations

US (1)