Optimizing Smoking Cessation for People With HIV/AIDS Who Smoke

The investigators propose a factorial design strategy to evaluate the effects, individually
and in combination, of the most promising pharmaco- and behavioral cessation therapies
available for PLWH according to the review of the extant literature for HIV-infected and
general population smokers. The sizable cohort and prospective design will also permit the
investigators to evaluate the effects of tobacco use, treatment, and cessation on a panel of
soluble biomarkers of inflammation that are likely contributors to cardiac morbidity and
mortality in people living with HIV/AIDS. The specific aims of the study are:

Primary Aim 1: Compare varenicline to placebo on rates of 7-day point prevalence abstinence
(PPA) at 24 weeks in smokers with HIV/AIDS. It is hypothesized that rates of smoking
abstinence at week 24 will be higher in those treated with varenicline compared to placebo.

Primary Aim 2: Compare Positively Smoke Free to low intensity, brief counseling on rates of
7-day PPA at 24 weeks in smokers with HIV/AIDS. It is hypothesized that rates of smoking
abstinence at week 24 will be higher in those treated with Positively Smoke Free compared to
brief counseling.

Secondary Aim: Compare Positively Smoke Free + varenicline to the other two study conditions
outlined above on rates of 7-day PPA in smokers with HIV/AIDS at 24 weeks. It is hypothesized
that the effect of PSF with varenicline is greater than the effect of PSF or varenicline
alone.

Exporatory Aim: Explore the effect of successful cessation/smoking abstinence on levels of
cardiac specific biomarkers, nicotine biomarkers, generalized markers of inflammation,
lipids, coagulation and monocyte/macrophage activation. The investigators hypothesize that
smoking cessation will be associated with significant reductions in levels of these
biomarkers and monocyte/macrophage activation.

Study Inclusion Criteria:

1. Confirmed chart diagnosis of a HIV and receiving HIV treatment at the participating
HIV clinic.

2. Age 18 years or older.

3. Currently self-report smoking 10 cigarettes per day

4. Motivation to quit within the next 6 months (score 5-8 on the Abrams and Briener
Readiness to Quit Ladder);

5. Does not meet criteria for current DSM 5 moderate or severe alcohol use disorder or
moderate or severe substance use disorder as established by the MINI drug and alcohol
sections (in the last 3 months)

6. Able to read and speak English

7. Willingness and ability to provide informed consent to participate.

Study Exclusion Criteria:

The exclusion criteria are designed to maximize safety by minimizing drug interactions or
worsening pre-existing comorbid psychiatric or medical conditions:

1. Current suicidal thoughts or ideation (past week); recent suicidal thoughts or
ideation (past 6 months) or recent suicide attempt (past 6 months) as assessed by the
Columbia-Suicide Severity Rating Scale (C-SSRS).

2. Previous allergic reaction or hypersensitivity to Varenicline (by participant report
ever in lifetime)

3. Pregnant, nursing, or becoming pregnant during the study (pregnancy test).

4. Current use of any medication that would interfere with the protocol in the opinion of
Medically Accountable Physician including use of bupropion targeting nicotine
dependence

5. Moderate to severe renal impairment (< 30 mL/min)--As determined by a physician
assessment, chart review or thru blood work

6. Unstable cardiovascular disease (myocardial infarction within past year, uncontrolled
arrhythmia, uncontrolled angina, uncontrolled congestive heart failure,
electrocardiogram abnormality with QTC > 500 msec, cerebrovascular event within past
year). (As determined by a physician assessment, chart review and/or EKG)

7. Meets criteria for dementia by scoring below 10 on the Hopkins HIV Dementia Scale.
This criterion is included to ensure the sample consists of participants who are
cognitively able to engage in the study procedures

8. Scores <5 ppm of expired carbon monoxide (CO) on the Smokelyzer

9. The study physician believes that the individual is not medially stable enough to
participate in the study. This exclusion will be based on a review of the individual's
past medical history and current medical status.

10. Recent use of Varenicline (by participant report in the past 3 months)