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

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.

Study Overview

• Status: Completed
• Conditions: Smoking; HIV; COPD

Detailed Description

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.

• Study Type: Observational
• Enrollment (Actual): 210

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Denver

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• 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.

Description

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.

Study Plan

How is the study designed?

Number of groups / cohorts

7

Cohorts and Interventions

Group / Cohort
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Collaborators and Investigators

• Sponsor: University of Colorado, Denver

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2014
• Primary Completion (Actual): July 1, 2019
• Study Completion (Actual): December 1, 2019

Study Registration Dates

• First Submitted: February 5, 2014
• First Submitted That Met QC Criteria: February 6, 2014
• First Posted (Estimate): February 10, 2014

Study Record Updates

• Last Update Posted (Actual): December 18, 2019
• Last Update Submitted That Met QC Criteria: December 16, 2019
• Last Verified: December 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases
• Other Study ID Numbers: 13-2986