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

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.

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Key information

Conditions

HIV Behavior COPD Chronic Disease Disease Attributes Lung Diseases Lung Diseases, Obstructive Pathologic Processes Pathological Conditions, Signs and Symptoms Pulmonary Disease, Chronic Obstructive Respiratory Tract Diseases Smoking

Age range

18 year–70 year

Sex eligibility

All sexes

Study type

Observational

Primary location

University of Colorado Denver

Aurora, Colorado, 80045, United States

About this study

The first component of this study will be a longitudinal, prospective, 24 weeks study of the effects of HIV-1 infection on innate and acquired immunity in the lung (Cohort A). The second component of this study will be a cross-sectional, case-control study of lung function and immune dysregulation of HIV-1 infected persons on long-term ART (Cohort B).

Cohort A will consist of 120 subjects, stratified by HIV-1 and smoking status

Cohort B will consist of 90 subjects stratified by chronic obstructive pulmonary disease (COPD) and HIV-1 infection.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

(Cohort A):

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)
18 years and older (All Cohort A)
Active cigarette smoker (Cohorts A1 and A3)

Inclusion criteria

(Cohort B):

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)

Exclusion criteria

(Cohort A and B):

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.

Treatment and study plan

Primary outcomes

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

Time frame: Baseline, Week 24

Evaluate the immunoregulatory change between HIV positive (smokers/non-smokers) and HIV negative (smokers/non-smokers)
PD-1 expression and IL-10 production by AMs at baseline

Time frame: 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.

Sponsors and collaborators

Lead sponsor

University of Colorado, Denver

Other

Registry information

Official study title

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

Important dates

Study start: 2014
Primary completion: 2019
Study completion: 2019
First posted: Feb 10, 2014
Registry last updated: Dec 18, 2019

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Published trials that share one or more normalized conditions with this study.

Completed