The purpose of this study is to learn how smoking affects the immune systems in people with HIV infection. The investigators would like to know if HIV infected smokers who quit smoking have different responses in their tissues from people who keep smoking.

For Aim 1, a total of up to 30 patients with HIV disease who have never smoked will be recruited, with recruitment stopping before 30 samples if the samples from 20 patients that can be used in analysis have been obtained. These 20 non-smoker samples will be compared to those of 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 participants have similar inclusion/exclusion criteria as this study and have been verified to be HIV-antibody negative. The investigators 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 30 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 30 subjects achieve successful smoking cessation. Just like for nonsmokers, recruitment for both smoker cohorts will stop before 30 if samples from 20 patients that can be used in analysis have been obtained. The maximum total number of patients needed for the grant is 130 (100 HIV smokers, 30 HIV non-smokers).

About130 participants will be recruited from the BMC Center for Infectious Diseases (CID) outpatient clinic, other outpatient clinics within BMC, affiliated community health centers (CHCs), BWH, MGH, Tufts Medical Center, and Beth Israel Deaconess Medical Center. The BMC CID 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. Participants will be recruited from flyers, the BMC ReSPECT registry, medical record screening, and physician referrals.

Inclusion criteria.

1. HIV infected on ART ≥ 6 months

2. Virologically suppressed (<50 cop/ml) at the time of enrollment (lab test within 3 months )

3. Smoking Status:

   Currently Active Smoker: Self-reported regular cigarette use with positive cotinine test at screening visit.

   OR Non-smoker: self-reported non-smokers confirmed by negative cotinine test at screening visit.

4. Laboratory values within 3 months prior to enrollment that meet the following criteria:

   1. Hemoglobin ≥ 8.0 g/dL
   2. Platelet count ≥ 80,000/mm3

5. For females of child-bearing potential: Negative urine pregnancy test (sensitive to 25 IU HCG) at screening visit.

For purposes of this study, a female is considered of child-bearing potential unless:

• Permanently sterile (includes hysterectomy, bilateral oophorectomy, or bilateral salpingectomy)
• Medically documented ovarian failure
• Post-menopausal, defined as ≥ 55 years of age with cessation of menses for ≥ 12 months

Exclusion criteria:

1. Pregnant or breast-feeding or less than 8 weeks post-partum.
2. Active malignancy and receiving concurrent treatment (i.e. chemotherapy, radiation therapy, investigational treatment).
3. Significant immunological illnesses/deficiencies
4. Recent active illness within the past 1 month (i.e. respiratory viral infection, pneumonia, bacterial infections, bone infection)
5. History of tuberculosis, lung cancer, bronchiectasis, pulmonary fibrosis, or pulmonary hypertension
6. 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. Reports of no such use within the past month will be confirmed by a urine tox screen performed at the Screening Visit.
7. Self-reported regular use of inhaled substances (such as crack, fentanyl, heroin, hookah, e-cigarettes) in the past (prior to 1 month ago and within the past 5 years), with use occurring for > 1 year. (Marijuana use is allowable.)
8. Spirometry criteria FEV1/FVC < 0.7 (definition of COPD) and GOLD (severe-very severe) Stage 3 or 4 within past 12 months
9. A history of alcohol dependence within the 6 months prior to enrollment
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 (within past 6 months). Non-coronary ischemia MI is allowed (i.e. cocaine-induced)
12. Chronic renal failure requiring dialysis
13. Decompensated cirrhosis
14. 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 and unable to stop for 48 hours prior to bronchoscopy
15. Taking any of the following medications within 30 days prior to enrollment: 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, anti-TNF agents
16. Recent abdominal surgery (within past 3 months)
17. Recent eye surgery (within past 3 months)
18. Investigator discretion