Interaction of Alcohol and Highly Active Antiretroviral Therapy (HAART) in HIV/AIDS and HIV/AIDS With Hepatitis C Virus (HCV) Co-Infection

The goal of this research study is to improve the clinical care of human immunodeficiency
virus (HIV)-infected or HIV/Hepatitis C (HCV) co-infected, alcohol-using patients by
identifying significant interactions which may occur between drugs commonly used to treat
HIV disease known to be cytochrome P450 (CYP450) inducers or inhibitors and alcohol, the
most frequently abused substance in the United States. We hypothesize that concomitant use
of alcohol and currently utilized antiretroviral therapy (ART) will be associated with
significant drug interactions including alteration of alcohol and ART pharmacokinetics as
well as altered responses to alcohol administration. We plan to conduct alcohol and ART
administration studies in 6 study samples (n=10 each): 1. those with HIV/AIDS and eligible
for efavirenz-containing HAART, 2. those with HIV/AIDS and eligible for a ritonavir-boosted
protease inhibitor based HAART, 3. those with HIV/AIDS and HCV eligible for an
efavirenz-containing HAART, 4. those with HIV/AIDS and HCV eligible for a ritonavir-boosted
protease inhibitor regimen, 5. healthy subjects taking clinically relevant doses of
maraviroc and 6. those with mild HCV taking clinically relevant doses of maraviroc.
Pharmacokinetics, subjective, and cognitive data will be serially collected over the course
of study sessions where either alcohol or placebo is administered prior to and following
ART. Data collected will elucidate the presence and clinical significance of drug
interactions, both pharmacokinetic and pharmacodynamic, between alcohol and ART in these
populations.

Inclusion Criteria:

- Participants will be diagnosed with HIV/AIDS, HIV/AIDS and Hepatitis C, mild
Hepatitis C or will be healthy as determined by history and physical examination,
screening laboratory tests and urinalysis, and will be eligible for treatment with
HAART

- Participants will be experienced with alcohol consumption

- They may meet diagnostic criteria for alcohol abuse or non-physiological alcohol
dependence, but may not be dependent on any other substances including opioids,
stimulants, cannabis, hallucinogens or other substances, prescribed or illicit

- For those with HCV coinfection, HCV must be at a stage consistent with no more than
mild liver fibrosis (fibrosis stage assessed by two methods: the AST to platelet
ratio (APRI) (at a score of <0.5 for eligibility) and the FIB-4 fibrosis index (score
of <1.5 for eligibility), both of which indicate mild liver disease.)

- Age 21 or older

- Hemoglobin Men > 11 g/dL, Women > 10 g/dL5

- Able to give voluntary, signed, informed consent.

Exclusion Criteria:

- Patients who are receiving concurrently other drugs that are inducers or inhibitors
of hepatic microsomal enzymes

- Patients with a known sensitivity to the HIV therapeutics to be studied

- Pregnant women or nursing mothers.

- All women who are sexually active and capable of becoming pregnant must have a
negative pregnancy test within one week prior to entry into these studies.

- Major psychotic illness or suicidality.

- Clinically active hepatitis with liver enzyme elevations > 3 times the upper limit of
normal or evidence of liver fibrosis at a stage indicative of greater than mild stage
for fibrosis (see Inclusion Criteria).

- Those with obesity (BMI > 30), diabetes, hyperlipidemia, coagulation disorders, or
renal disease will be excluded.

- Hemoglobin Men < 11 g/dL, Women < 10 g/dL

- Physical dependence on alcohol.