30-to-90 Day Challenge: Effects of Alcohol Cessation on Health Outcomes

This proposed study continues a line of research by Doctors Cohen, Cook, Kahler, and
colleagues on heavy alcohol use, HIV-associated brain dysfunction, and long-term HIV
outcomes. The study will build on our past findings to determine the extent to which marked
reductions in alcohol consumption at 30 days and again at 90 days via contingency management
(CM) improves cognitive-behavioral performance, underlying brain functions and
pathophysiology, and HIV-associated health outcomes. This feature in itself is a novel
contribution and has rarely been done, but more importantly, it reflects the mission of the
collaboration to develop actionable data on clinical trajectories in HIV infected heavy
drinkers over age 50 that will instill high confidence in guiding next therapeutic steps. The
study team will obtain a better understanding of how persons with HIV stop drinking, and what
factors influence long-term drinking changes. These important clinical and scientific
questions need resolution for successful treatment and management of HIV+ adults. This study
is motivated by evidence that HIV-associated neurocognitive dysfunction continues despite
effective combined anti-retroviral therapies (cART). Even mild cognitive impairments have
detrimental functional effects and health outcomes that worsen as HIV+ people age. Heavy
alcohol consumption is common among HIV+ adults, and contributes to functional brain
disturbances directly or indirectly via systemic metabolic or inflammatory disturbances.
However, our past findings indicate that current alcohol use is more strongly associated with
cognitive and brain dysfunction among HIV+ adults than lifetime consumption; and that adverse
brain effects occur primarily with heavy drinking. Our overarching hypothesis is that the
impact of ongoing heavy alcohol use on the brain and cognition may be reversible, providing a
strong impetus for the proposed study. The study team will conduct our research in Florida,
which has the highest number of new HIV infections in the US, as well as an increasingly
diverse population with HIV+, 50% of whom are now aged 50 years or over in the state.

Our research will seek to modify alcohol consumption by using contingency management (CM) and
measure for changes in brain pathophysiology and function, as well as changes in systemic
inflammation, and gut and liver pathologies which are hypothesized pathways by which alcohol
may increase brain dysfunction. The study team will also measure neurocognitive functioning
related to learning, attention-executive functions, working memory, and processing speed,
domains in which HIV+ persons experience persistent impairment. the study team will use
Motivational Interviewing (MI) to learn more about how persons with and without HIV reduce
drinking, what factors are associated with long-term drinking changes, and how these drinking
changes influence HIV clinical health behavior and outcomes. If the impact of alcohol on
systemic and cerebral inflammation is temporary, then reducing or eliminating alcohol
consumption could dramatically improve cognitive function and indices of brain health, even
among people who have consumed alcohol for many years in the past. Our research will directly
test hypotheses that ongoing heavy alcohol consumption is associated with brain
pathophysiology and inflammation that impairs both functioning and cognitive processing, and
that the inflammation and its sequelae are reversible in most HIV+ persons with alcohol
cessation. The proposed sample will be 140 adults with HIV infection and 40 adults without
HIV infection (at least 25% female; age >50 years). Participants will be recruited from heavy
drinkers (>=14 drinks/week women, >=21 drinks/week men) with HIV infection identified from
our ongoing Florida Cohort. HIV- participants will be recruited from community medical
clinics where flyers will be posted.

Inclusion Criteria:

1. Men and women;

2. Age: 50-75 yrs.;

3. 140 participants will have confirmed HIV (confirmed via baseline bloodwork) and 40
participants will be HIV negative

4. English speaking (will have protocol ready in Spanish in 2017);

5. Physically mobile;

6. Willing to participate in CM to reduce alcohol consumption, and to wear the alcohol
biosensor for at least 30 days. All participants will be current, heavy drinkers (>=14
drinks/week women, >=21 drinks/week men), confirmed by baseline timeline follow-back,
and by having evidence of at least 3 drinking episodes on the alcohol biosensor prior
to baseline). Must blow a "zero" on breathalyzer at time of informed consent

Exclusion Criteria:

1. Neurological disorders (e.g., dementia, stroke, seizures, traumatic brain injury).

2. Evidence of dementia (MOCA < 17).

3. Past opportunistic brain infection

4. Major psychiatric illness (schizophrenia, intractable affective disorder, current
substance dependence diagnosis).

5. Current major psychiatric disturbance, including severe major depression.

6. Unstable medical conditions (e.g., cancer).

7. MRI contraindications (e.g., pregnancy, severe claustrophobia, metal implants).

8. Physical impairment precluding motor response or lying still.

9. Significant history of alcohol withdrawal as indicated by an Alcohol Withdrawal
Symptom Checklist score ≥ 23 (within past year).

10. Unable to correctly answer a set of questions that demonstrate understanding of key
aspects of the study, including the voluntary nature of the study, the purpose of the
study, what participants are being asked to do as part of the study, and what are the
risks related to participating in the study.