Impact of Smoking and Its Cessation on Systemic and Airway Immune Activation

For Aim 1, 20 patients with HIV disease who have never smoked will be recruited with
comparison to 20 active smokers with HIV disease, without evidence of COPD from spirometry,
who are matched in demographics. Smokers who are interested in participating in a smoking
cessation program will be referred to our Clinical Trials Unit (CTU) for all subsequent study
visits.

Additionally, a comparison group of 20 uninfected smokers who have already been enrolled in
the co-investigator's (Dr. Kwon) study will be used as comparison group. These patients have
similar inclusion/exclusion criteria as this study and have been verified to be HIV-antibody
negative. We will obtain de-identified samples and immunological and virological data already
collected by Dr. Kwon. De-identified banked PBMC, plasma and BAL samples will also be
accessible to us using a material transfer agreement to perform epithelial transcriptional
gene expression profiling.

For Aim 2, a total of 100 HIV-infected individuals on effective ART who are active smokers
and interested in participating in a smoking cessation program will be recruited. If 20
individuals who achieve 10-week of cessation are enrolled before 100 HIV smokers are fully
enrolled, enrollment will cease, as 100 participants is an overestimate of the number of
patients needed need to enroll to have 20 subjects achieve successful smoking cessation. The
maximum total number of patients needed for the grant is 120 (100 HIV smokers, 20 HIV
non-smokers).

We will recruit up to 120 patients from the BMC Center for Infectious Diseases (CID)
outpatient clinic. The clinic serves the largest HIV-infected population in Boston,
approximately 1,700 persons, and is composed largely of an urban socioeconomically
disadvantaged population. Over 50% of HIV-infected patients in the CID are smokers, and >60%
(based on prescription history of NRT, bupropion, varenicline) have attempted smoking
cessation. We will recruit from flyers, the BMC ReSPECT registry, medical record screening,
and physician referrals. A listing of the trial will also be posted on clinicaltrials.gov.

To be eligible for this study, participants must be a patient at BMC and meet all of the
following inclusion criteria.

1. Ages 18-75

2. HIV infected on ART ≥ 6 months and virologically suppressed (<50 cop/ml) at the time
of enrollment (lab test within 3 months )

3. Currently active smoker with self-reported ≥5 cigarettes per day most days of the week
and confirmed by positive salivary cotinine verification at screening.

4. Aim 1 self-reported non-smokers will be confirmed by salivary cotinine verification at
screening.

5. Laboratory values within 60 days prior to enrollment that meet the following criteria:

1. Hemoglobin ≥ 10.0 g/dL

2. Absolute neutrophil count ≥ 1000/mm3

3. Platelet count ≥ 80,000/mm3

6. Negative urine pregnancy test (sensitive to 25 IU HCG) at screening and within 24
hours of the study procedure for female participants

7. Ability and willingness to give written informed consent and to comply with study
requirements.

Participants will be excluded from this study if:

1. Pregnant or breast-feeding or less than 8 weeks post-partum.

2. Active malignancy

3. Significant immunological illnesses/deficiencies

4. Use of any immunomodulatory agents within 30 days prior to study enrollment.

5. Recent active illness (2 months)

6. History of tuberculosis, lung cancer, bronchiectasis, pulmonary fibrosis, and
pulmonary hypertension

7. Self-reported regular or recreational use of inhaled substances (such as marijuana,
crack, fentanyl, heroin, hookah, e-cigarettes) as well as chewing tobacco within past
month

8. COPD GOLD Stage 3-4 based on screening spirometry. Subjects who meet all the inclusion
and exclusion criteria will undergo spirometry.

1. Aim 1: Only HIV smokers with no diagnosis of COPD; normal spirometry and FEV1/FVC
>0.7.

2. Aim 2: HIV smokers with evidence of COPD GOLD Stage 1-2 (mild-moderate) can be
enrolled.

3. All screened participants with known COPD or spirometry diagnosis of GOLD Stage
3-4 will be excluded due to safety of bronchoscopy.

9. A history of alcohol dependence within the 6 months prior to the screening visit.

10. History of intolerance, sensitivity, allergy or anaphylaxis to lidocaine or other
amide anesthetics, as well as benzocaine or other ester type anesthetics.

11. History of recent myocardial infarction, chronic renal failure requiring dialysis,
decompensated cirrhosis, or any other condition that in the opinion of the
investigator will compromise ability to participate in the study.

12. Currently taking anticoagulants including but not limited to: heparin (Hep-Lock,
Hep-Pak), Hep-Pak CVC, Heparin Lock Flush), warfarin (Coumadin), tinzaparin (Innohep),
enoxaparin (Lovenox), danaparoid (Orgaran), dalteparin (Fragmin), clopidogrel
(Plavix), prophylactic aspirin, and NSAID use 48 hours prior to bronchoscopy.

13. Subject taking any of the following medications: systemic steroids (inhaled or nasal
steroid therapy is permitted), interleukins, systemic interferons (e.g., local
injection of interferon alpha for treatment of HPV is permitted) or systemic
chemotherapy.

14. Prior recipient of HIV vaccine.

15. Recent abdominal or cataract surgery

16. Investigator discretion Note: If subject reports current symptoms of upper respiratory
infection, study start will be delayed 1 week or until symptoms are resolved.