Varenicline for Nicotine Dependence Among Those With HIV/AIDS

Among people diagnosed with HIV/AIDS, the widespread use of highly active antiretroviral
therapy (HAART) has greatly improved survival rates and changed the leading causes of death,
from AIDS-related diseases (e.g., non-Hodgkin's lymphoma, Kaposi sarcoma), to cardiovascular
disease and lung cancer. As such, addressing modifiable risk factors for disease mortality
among those with HIV/AIDS, including tobacco use, has become a critical priority. To date,
only three smoking cessation clinical trials have been conducted with those with HIV/AIDS
none of which investigated the efficacy of FDA-approved medications for nicotine dependence.
Varenicline is an α4β2 nicotinic acetylcholine receptor partial agonist with greater efficacy
for treating nicotine dependence than bupropion or nicotine patch. Varenicline may be
particularly efficacious for treating nicotine dependence among individuals with HIV/AIDS
given that depression symptoms and cognitive impairment are common in this population,
increase during smoking abstinence and predict smoking relapse, and are significantly reduced
by varenicline. Therefore, the investigators will conduct a randomized, double-blind,
placebo-controlled trial of varenicline with smokers with HIV/AIDS. Specifically, 310 smokers
with HIV/AIDS will be randomized to varenicline plus 9 weeks of smoking cessation counseling
or placebo plus 9 weeks of smoking cessation counseling. The primary outcome variable for
this study will be 7-day biochemically confirmed tobacco abstinence at weeks 12 and 24.
Secondary outcomes include: prolonged abstinence to week 12, 18, and 24 (relapse defined as 7
consecutive days of self-reported smoking, after a 2-week grace period), continuous
abstinence at weeks 12 and 24 (e.g., no smoking between quit day and follow-up), time to
7-day relapse (no grace period), and lapse and recovery events. The trial results may support
the use of varenicline for the treatment of nicotine dependence among those with HIV/AIDS,
thereby reducing tobacco-related morbidity and mortality in this population.

Inclusion Criteria

1. 18 years of age or older who self-report smoking at least 5 cigarettes (menthol and
non-menthol) per day, on average.

2. Diagnosed with HIV infection and exhibiting viral load of < 1000 copies/mL and CD4+
counts of > 200 cells/mm3 within 6 months prior to enrollment.

3. Able to use varenicline safely, based on a medical evaluation including medical
history and physical examination, and psychiatric evaluation.

4. Residing in the geographic area for at least 7 months.

5. Women of childbearing potential (based on medical history and physical exam) must
consent to use a medically accepted method of birth control (e.g., condoms and
spermicide, oral contraceptive, Depo-Provera injection, contraceptive patch, tubal
ligation) or abstain from sexual intercourse during the time they are taking study
medication and for at least one month after the medication period ends.

6. If current or past diagnosis of bipolar disorder (I, II, or NOS), eligible if:

1. No psychotic features

2. MADRS: total score < 8 (past 4 weeks), suicidal item score < 1 (past 4 weeks)

3. Y-MRS: total score < 8 (past 4 weeks), irritability, speech content, disruptive,
or aggressive behavior items score < 3 (past 4 weeks)

4. No psychiatric hospitalization or Emergency Room visits for psychiatric issues in
the past 6 months

5. No aggressive or violent acts or behavior in the past 6 months

7. Able to communicate fluently in English.

8. Capable of giving written informed consent, which includes compliance with the
requirements and restrictions listed in the combined consent/HIPAA form.

Exclusion Criteria:

Smoking Behavior

1. Current enrollment or plans to enroll in another smoking cessation program in the next
7 months.

2. Regular (daily) use of chewing tobacco, snuff, snus, cigars, cigarillos, or pipes.

3. Current use or plans to use nicotine substitutes (gum, patch, lozenge, e-cigarette) or
smoking cessation treatments in the next 7 months.

1. Note: Once participants are found eligible for the study, they are told they
should refrain from using any nicotine replacement therapy (NRT) for the duration
of the study. If a subject reports an isolated (non-daily) instance of NRT use
during the study, they may be permitted to continue.

Alcohol/Drug Exclusion Criteria

1. Current untreated and unstable diagnosis of substance abuse or dependence (eligible if
past use and if receiving treatment and stable for >30 days).

2. Positive urine drug screen (for cocaine and/or methamphetamines) at the Intake
Session.

3. Breath Alcohol Concentration (BrAC) assessment greater than or equal to 0.01 at the
Intake Session.

Medication Exclusion Criteria

Current use or recent discontinuation (within last 14 days) of the following medications:

1. Other smoking cessation medications (e.g. Zyban, Wellbutrin, Wellbutrin SR, Chantix)

a. Note: Once participants are found eligible for the study, they are instructed to
only use the smoking cessation medication provided to them by the study staff. If a
subject reports an isolated (non-daily) instance of using a non-study smoking
cessation medication, the study physician and PI will evaluate the situation and
determine if it is safe for the subject to continue participation.

2. Anti-psychotic medications.

Medical Exclusion Criteria

1. Women who are pregnant, planning a pregnancy within the next 7 months, or lactating.

2. Current diagnosis of unstable and untreated major depression, as determined by
self-report & MINI (eligible if stable for >30 days).

3. Current or past diagnosis of psychotic disorder, as determined by self-report or MINI.

4. Any suicide risk score on MINI, current suicidal ideation on Columbia scale, or
self-reported lifetime suicide attempt.

5. History of heart disease, stroke or MI, unstable angina, or tachycardia (if stable,
requires Study Physician approval).

6. Uncontrolled hypertension (SBP >160 or DBP >100).

a. Note: If a participant presents with blood pressure greater than 160/100 at
sessions occurring on Week 0 (Pre-Quit) or at any other point during the treatment
period, they will not be provided with/able to continue on medication unless the study
physician grants approval.

7. History of kidney or liver failure.

8. Abnormal ECG (unless approved by study physician).

9. Estimated creatinine clearance <50 mL/min, within 6 months prior to enrollment.

10. AST and/or ALT results greater than 2 times the upper limit of normal, within 6 months
prior to enrollment.

11. Any impairment (physical, neurological, visual) preventing cognitive task performance.

12. Previous allergic reaction to varenicline.

General Exclusion Criteria

1. Any medical condition or concomitant medication that could compromise subject safety
or treatment, as determined by the Principal Investigator and/or Study Physician.

2. Inability to provide informed consent or complete any of the study tasks as determined
by the Principal Investigator and/or Study Physician.