Zidovudine Levels in HIV Infected Patients Being Treated for HCV - Full Text View

Purpose

This study will test the amount of anti-HIV drugs in the blood cells of HIV-infected patients who are also being treated for hepatitis C virus (HCV) infection.

Condition	Intervention	Phase
HIV Infections Hepatitis C	Drug: Ribavirin plus interferon alfa-2b Drug: Ribavirin Drug: Peginterferon alfa-2b	Phase 1 Phase 2


Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Intervention Model: Single Group Assignment Masking: None (Open Label) Primary Purpose: Treatment
Official Title:	Pharmacological Interactions Between Zidovudine and Ribavirin in HCV-HIV Co-Infected Patients Treated With Rebetron or Peg-Intron Plus Ribavirin

Resource links provided by NLM:

MedlinePlus related topics: HIV/AIDS Hepatitis Hepatitis C

Drug Information available for: Zidovudine Ribavirin Peginterferon Alfa-2b

U.S. FDA Resources

Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures:

Steady state area under the concentration time curve (AUC) between 0 and 12 hours of zidovudine (ZDV)-MP, ZDV-TP, and dTTP in PBMCs from HIV and hepatitis C virus (HCV) coinfected patients before and after peginterferon alfa-2b with or without ribavirin [ Time Frame: Throughout study ]
Systemic exposure (AUC over 0 to 12 hours) of nelfinavir before and after peginterferon alfa-2b with or without ribavirin in HIV and HCV coinfected patients [ Time Frame: Throughout study ]
Effect of peginterferon alfa-2b with or without ribavirin in HCV RNA viral titers, alanine aminotransferase (ALT) levels, CD4+, and HIV-RNA viral titers in HIV and HCV coinfected patients [ Time Frame: Through Week 48 ]
Effect of peginterferon alfa-2b with or without ribavirin on liver histology [ Time Frame: At Week 72 ]


Estimated Enrollment:	16
Study Start Date:	September 2001
Study Completion Date:	June 2005
Primary Completion Date:	June 2005 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 1 Participants will begin receive either Rebetron or PEG-Intron plus ribavirin therapy from Weeks 2 through 48	Drug: Ribavirin plus interferon alfa-2b Oral tablets taken daily Drug: Ribavirin Oral tablet taken daily Drug: Peginterferon alfa-2b Subcutaneous injection

Detailed Description:

An estimated 50,000 people in Puerto Rico are infected with HCV. HIV and HCV have similar routes of transmission, and HCV co-infection occurs in 8% to 23% of HIV infected patients. Researchers have shown that treatment for HCV with Rebetron (ribavirin plus interferon alfa-2b) significantly decreases HCV viral load without affecting HIV viral load. However, measurements of intracellular levels of the active forms of zidovudine (ZDV-MP and ZDV-TP) were not performed. Such measurements are needed to provide a more rational basis for dosing in HIV/HCV co-infected patients. This study will investigate the intracellular exposure to active ZDV metabolites prior to and after treatment with Rebetron or treatment with PEG-Intron (pegylated interferon) and ribavirin.

Participants in this study will remain on their usual antiretroviral regimen; no changes may be made to that regimen for the first 4 weeks of the study. Upon study entry, participants will have intracellular pharmacokinetic studies. During Week 2, participants will start either Rebetron or PEG-Intron plus ribavirin therapy, will have intracellular pharmacokinetic studies, and will undergo liver biopsy. Additional intracellular pharmacokinetic studies will be performed at Weeks 12 and 24. Rebetron or PEG-Intron plus ribavirin will be given for 48 weeks. A second liver biopsy will be performed 24 weeks after discontinuing Rebetron or PEG-Intron plus ribavirin therapy. Participants will be followed for 72 weeks.

Eligibility


Ages Eligible for Study:	21 Years to 60 Years (Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria

HCV-infected
HIV-1 infection
CD4 cell count > 200 cells/mm³ within 30 days prior to study entry
HIV RNA < 400 copies/ml within 90 days of study entry
Use of zidovudine, lamivudine, and any PI and/or NNRTI
ANC value >= 1,500 ml³ within 30 days of study entry
Weight > 50 kg (110 lbs) for women and > 60 kg (132 lbs) for men
Acceptable methods of contraception
Ability and willingness to complete the Baseline Adherence Questionnaire
Documentation of adherence confirmed by the Baseline Adherence Questionnaire and certified by the study officials

Exclusion Criteria

Previous ribavirin therapy
More than 2 months of interferon therapy
Current use of any NRTI other than ZDV and 3TC
Hepatitis B surface antigen positive
Infectious, autoimmune, tumoral, biliary, or vascular liver disease
Alcohol consumption of more than 50 g/day
Current use of intravenous drugs
Hemoglobin levels < 10 gm/dl
Methadone use
Chemotherapy
Certain medications
Acute opportunistic or bacterial infection requiring therapy at the time of enrollment
Hemoglobinopathy (e.g., thalassemia) or any other cause of tendency to hemolysis
Psychiatric disorders, severe depression, history of suicide attempts, or suicidal ideation
Renal disease requiring dialysis
Significant coronary diseases or two or more risk factors for coronary diseases, such as > 55 years old, hypertension, and cholesterol > 250 mg/dl
Any clinically significant diseases (other than HIV and HCV infection) that, in the opinion of study officials, would compromise the outcome of this study
Pregnancy
Participation in blinded clinical trial

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: NCT00059358

Locations


Puerto Rico
UPR Adult ACTU
San Juan, Puerto Rico, 00936-5067

Sponsors and Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

Investigators


Principal Investigator:	Jose F. Rodriguez, PhD	MSC-UPR
Principal Investigator:	Jorge L. Santana, MD	MSC-UPR

More Information


Responsible Party:	Jose F. Rodriguez, PhD, MSC-UPR
ClinicalTrials.gov Identifier:	NCT00059358 History of Changes
Other Study ID Numbers:	1R01AI09141-01A1 5R01AI049141-02 ( U.S. NIH Grant/Contract )
Study First Received:	April 23, 2003
Last Updated:	August 6, 2009

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):


HIV HCV Ribavirin	Interferon Co-infection Treatment experienced

Additional relevant MeSH terms:


Hepatitis C HIV Infections Hepatitis, Viral, Human Virus Diseases Flaviviridae Infections RNA Virus Infections Hepatitis Liver Diseases Digestive System Diseases Lentivirus Infections Retroviridae Infections Sexually Transmitted Diseases, Viral Sexually Transmitted Diseases Immunologic Deficiency Syndromes Immune System Diseases	Interferons Ribavirin Interferon-alpha Zidovudine Peginterferon alfa-2b Antineoplastic Agents Antiviral Agents Anti-Infective Agents Antimetabolites Molecular Mechanisms of Pharmacological Action Immunologic Factors Physiological Effects of Drugs Reverse Transcriptase Inhibitors Nucleic Acid Synthesis Inhibitors Enzyme Inhibitors

ClinicalTrials.gov processed this record on September 21, 2017