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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
University of California, San Francisco
ClinicalTrials.gov Identifier:
NCT00879047
First received: March 24, 2009
Last updated: May 2, 2014
Last verified: May 2014
  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 Phase
HIV Infections
Hepatitis C
Drug: Alcohol
Drug: Alcohol placebo
Phase 1

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

Resource links provided by NLM:


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 ]

Enrollment: 30
Study Start Date: April 2009
Study Completion Date: April 2013
Primary Completion Date: April 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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

Locations
United States, California
University of California, San Francisco
San Francisco, California, United States, 94115
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: May 2, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by University of California, San Francisco:
HIV
Hepatitis C

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
Coinfection
Communicable Diseases
Hepatitis
Hepatitis A
Hepatitis C
HIV Infections
Infection
Digestive System Diseases
Enterovirus Infections
Flaviviridae Infections
Hepatitis, Viral, Human
Immune System Diseases
Immunologic Deficiency Syndromes
Lentivirus Infections
Liver Diseases
Parasitic Diseases
Picornaviridae Infections
Retroviridae Infections
RNA Virus Infections
Sexually Transmitted Diseases
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Virus Diseases
Efavirenz
Ethanol
Ritonavir
Anti-HIV Agents
Anti-Infective Agents
Anti-Infective Agents, Local

ClinicalTrials.gov processed this record on October 22, 2014