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

Purpose

The proposed studies will examine the extent of pharmacokinetic and pharmacodynamic interactions between alcohol and various antiretroviral therapies in those with HIV/AIDS, HIV/HCV co-infection, mild HCV and healthy subjects.

Condition	Intervention
HIV Infections Hepatitis C	Drug: Alcohol Drug: Alcohol placebo

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Pharmacokinetics/Dynamics Study Intervention Model: Crossover Assignment Masking: Double Blind (Subject, Investigator) Primary Purpose: Basic Science
Official Title:	Interaction of Alcohol & HAART in HIV/AIDS and HIV/AIDS With HCV Co-Infection

Resource links provided by NLM:

Genetics Home Reference related topics: complement factor I deficiency

MedlinePlus related topics: Drug Reactions HIV/AIDS HIV/AIDS Medicines Hepatitis Hepatitis A Hepatitis C

Drug Information available for: Efavirenz Ritonavir

U.S. FDA Resources

Further study details as provided by University of California, San Francisco:

Primary Outcome Measures:

Plasma levels of antiretroviral medications. [ Time Frame: Baseline, two weeks, and three weeks. ] [ Designated as safety issue: No ]
Plasma levels of alcohol. [ Time Frame: Baseline, two weeks, and three weeks. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Measures of cognitive and behavioral change/impairment. [ Time Frame: Baseline, two weeks, and three weeks. ] [ Designated as safety issue: No ]

Estimated Enrollment:	60
Study Start Date:	April 2009
Estimated Study Completion Date:	May 2013
Estimated Primary Completion Date:	May 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: HIV+, Ritonavir-regimen 10 subjects will be HIV+ and will begin receiving Ritonavir-containing regimen, and their PK interactions with alcohol/placebo will be evaluated.	Drug: Alcohol Consumed orally as liquid mixed with a juice beverage, 1 g/kg formula, administered once at baseline and again at either 2 or 3 weeks Other Name: grain alcohol Drug: Alcohol placebo Liquid alcohol spritzed on top of juice beverage immediately prior to administration in order to give smell of alcohol, administered once at baseline and again at either 2 or 3 weeks Other Name: grain alcohol
Experimental: HIV+/HCV+ Co-infected, Ritonavir-regimen 10 subjects will be HIV+/HCV+ co-infected and will begin receiving Ritonavir-containing regimen, and their PK interactions with alcohol/placebo will be evaluated.	Drug: Alcohol Consumed orally as liquid mixed with a juice beverage, 1 g/kg formula, administered once at baseline and again at either 2 or 3 weeks Other Name: grain alcohol Drug: Alcohol placebo Liquid alcohol spritzed on top of juice beverage immediately prior to administration in order to give smell of alcohol, administered once at baseline and again at either 2 or 3 weeks Other Name: grain alcohol
Experimental: HIV+, Efavirenz-regimen 10 subjects will be HIV+ and will begin receiving Efavirenz-containing regimen, and their PK interactions with alcohol/placebo will be evaluated.	Drug: Alcohol Consumed orally as liquid mixed with a juice beverage, 1 g/kg formula, administered once at baseline and again at either 2 or 3 weeks Other Name: grain alcohol Drug: Alcohol placebo Liquid alcohol spritzed on top of juice beverage immediately prior to administration in order to give smell of alcohol, administered once at baseline and again at either 2 or 3 weeks Other Name: grain alcohol
Experimental: HIV+/HCV+ Co-infected, Efavirenz-regimen 10 subjects will be HIV+/HCV+ co-infected and will begin receiving Efavirenz-containing regimen, and their PK interactions with alcohol/placebo will be evaluated.	Drug: Alcohol Consumed orally as liquid mixed with a juice beverage, 1 g/kg formula, administered once at baseline and again at either 2 or 3 weeks Other Name: grain alcohol Drug: Alcohol placebo Liquid alcohol spritzed on top of juice beverage immediately prior to administration in order to give smell of alcohol, administered once at baseline and again at either 2 or 3 weeks Other Name: grain alcohol
Experimental: Maraviroc in Healthy Subjects 10 healthy subjects will begin receiving maraviroc, and their PK interactions with alcohol/placebo will be evaluated.	Drug: Alcohol Consumed orally as liquid mixed with a juice beverage, 1 g/kg formula, administered once at baseline and again at either 2 or 3 weeks Other Name: grain alcohol Drug: Alcohol placebo Liquid alcohol spritzed on top of juice beverage immediately prior to administration in order to give smell of alcohol, administered once at baseline and again at either 2 or 3 weeks Other Name: grain alcohol

Detailed Description:

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.

Eligibility

Ages Eligible for Study:	21 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

Criteria

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00879047

Contacts

Contact: Vincent Samson, B.A.

415-206-3362

vincent.samson@ucsf.edu

Locations

United States, California
University of California, San Francisco	Recruiting
San Francisco, California, United States, 94115
Contact: Elinore F McCance-Katz, M.D., Ph.D. 415-206-4010 Elinore.Mccance-katz@ucsf.edu

Sponsors and Collaborators

University of California, San Francisco

Investigators

Principal Investigator:

Elinore F McCance-Katz, M.D., Ph.D.

University of California, San Francisco

More Information

No publications provided

Responsible Party:	University of California, San Francisco
ClinicalTrials.gov Identifier:	NCT00879047 History of Changes
Other Study ID Numbers:	R01AA018001
Study First Received:	March 24, 2009
Last Updated:	October 18, 2012
Health Authority:	United States: Institutional Review Board

Keywords provided by University of California, San Francisco:

HIV
Hepatitis C

Additional relevant MeSH terms:

HIV Infections
Acquired Immunodeficiency Syndrome
Hepatitis
Hepatitis A
Hepatitis C
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Liver Diseases

Digestive System Diseases
Hepatitis, Viral, Human
Enterovirus Infections
Picornaviridae Infections
Flaviviridae Infections
Ethanol
Efavirenz
Anti-Infective Agents, Local
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Central Nervous System Depressants
Physiological Effects of Drugs
Central Nervous System Agents
Reverse Transcriptase Inhibitors

ClinicalTrials.gov processed this record on March 03, 2013