Cognition and Smoking Relapse (HCS)

Medical advances in the treatment of HIV/AIDS have improved the life expectancy of
HIV-infected individuals. Unfortunately, HIV-infected individuals are three times more likely
to use tobacco than those in the general population, but little is known about the mechanisms
that underlie these high smoking rates. This will be the first study to test whether the
neurocognitive impairments associated with HIV-1 infection may be exacerbated during nicotine
withdrawal and increase the probability of smoking relapse among HIV-infected smokers (HIV+),
compared to HIV-uninfected smokers (HIV-). To this end, adult treatment-seeking smokers
(N=300; 150 HIV+ and 150 HIV-) will complete this 12-week study, which is divided into two
phases: a pre-quit laboratory phase (weeks 0-2) and a treatment phase (weeks 3-12). Subjects
will complete two laboratory sessions during the pre-quit phase: once following 24 hours of
mandatory smoking abstinence and once while smoking-as-usual (order counterbalanced). A
comprehensive cognitive task battery assessing memory, attention, and executive function will
be administered during each laboratory session. During the treatment phase, all subjects will
receive standard smoking cessation treatment, including counseling (weeks 3-8) and open-label
transdermal nicotine (TN) patches (weeks 4-12). The primary outcomes are: 1) cognitive
performance following 24-hours smoking abstinence (vs. smoking-as-usual) during the pre-quit
phase; and 2) 7-day point-prevalence, biochemically-confirmed abstinence rates at the
end-of-treatment (EOT) for the treatment phase.

Inclusion Criteria:

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

- HIV status

1. HIV-infected smokers: diagnosed with HIV infection and exhibiting viral load of
less than or equal to 1000 copies/mL and CD4+ counts of greater than or equal to
200 cells/mm3 within 6 months prior to enrollment.

2. HIV-uninfected smokers: negative HIV status will be confirmed by an on-site rapid
HIV blood test.

- Able to use transdermal nicotine (TN) safely, based on a medical evaluation.

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

- Women of childbearing potential (based on medical history) 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 in the study and using transdermal
nicotine.

- Able to communicate fluently in English.

- 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
4 months.

2. Regular (daily) use of electronic cigarettes, 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 4 months.

Alcohol/Drug Exclusion Criteria

1. Current untreated and unstable diagnosis of substance dependence (eligible if past use
and if receiving treatment and stable for at least 30 days). Current untreated and
unstable diagnosis of substance abuse requires Study Physician approval.

2. Breath Alcohol Concentration (BrAC) assessment greater than 0.00 at the Intake
session, Lab Session 1, or Lab Session 2.

3. A positive urine drug screen for cocaine, amphetamines, methamphetamines,
Phencyclidine (PCP), barbiturates, ecstasy (MDMA) at Intake, Lab Session 1 or Lab
Session 2 (see Measures and Table 1 for details).

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 sustained
release (SR), Chantix)

a. Note: Once participants are found eligible for the study, they are instructed to
only use the NRT provided to them by the study staff. If a subject reports using a
non-study smoking cessation medication (including other forms of NRT), 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 (if used to treat psychotic symptoms. Other uses may be
eligible pending physician approval).

3. Daily use of opiate-containing medications for chronic pain (Duragesic/fentanyl
patches, Percocet, Oxycontin). Smokers who report taking opiate-containing medications
on an "as-needed" basis will be instructed to refrain from use until their study
participation is over and that they will be tested to ensure they have complied with
this requirement.

4. Asthma medications/corticosteroids (requires physician approval)

5. Anti-depressants (require physician approval)

Medical Exclusion Criteria

1. Females who self-report current pregnancy, planning a pregnancy during the study, or
currently breastfeeding/lactating.

2. Current diagnosis of unstable and untreated major depression, as determined by
self-report & Mini International Neuropsychiatric Interview (MINI) (eligible if stable
for at least 30 days).

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

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

5. Uncontrolled hypertension (systolic blood pressure (SBP) greater than 160 or diastolic
blood pressure (DBP) greater than 100) present at Intake.

a. Note: If a participant presents with blood pressure greater than 160/100 at
sessions occurring on Week 3 (Pre-Quit) or at any other point during the treatment
period, they will not be provided with/able to continue on TN unless the study
physician grants approval.

6. Previous allergic reaction to TN or to latex.

7. History of diabetes (requires Study Physician approval)

8. History of seizures (requires Study Physician approval)

9. History of stomach ulcers (requires Study Physician approval)

Suicide History Exclusion Criteria

1. Any suicide attempt or suicidal behavior within 2 years of enrollment.

a. Note: Any participant that reports a suicide attempt or episode of suicidal
behavior more than 2 years before enrollment will be evaluated by senior clinical
staff (Dr. Hole or Dr. Ashare) to assess final eligibility based on the complete
psychological profile ascertained at the intake session.

2. Current suicidal ideation (within the last 30 days of enrollment).

3. Two or more lifetime suicide attempts or episodes of suicidal behavior.

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. Color blindness.

3. Any impairment (physical and/or neurological) including visual or other impairment
preventing cognitive task performance.

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