Zidovudine Levels in HIV Infected Patients Being Treated for HCV

HIV Infections Clinical Trial

Official title:

Pharmacological Interactions Between Zidovudine and Ribavirin in HCV-HIV Co-Infected Patients Treated With Rebetron or Peg-Intron Plus Ribavirin

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00059358
• Other study ID #: 1R01AI09141-01A1
• Secondary ID: 5R01AI049141-02
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: April 23, 2003
• Last updated: August 6, 2009
• Start date: September 2001
• Est. completion date: June 2005

Study information

• Verified date: August 2009
• Source: National Institute of Allergy and Infectious Diseases (NIAID)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 16
• Est. completion date: June 2005
• Est. primary completion date: June 2005
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 21 Years to 60 Years

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hepatitis C
• HIV Infections

Intervention

Drug:
• Ribavirin plus interferon alfa-2b
Oral tablets taken daily
• Ribavirin
Oral tablet taken daily
• Peginterferon alfa-2b
Subcutaneous injection

Locations

Country	Name	City	State
Puerto Rico	UPR Adult ACTU	San Juan

Sponsors (1)

Lead Sponsor	Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)

Country where clinical trial is conducted

Puerto Rico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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		Throughout study	No
Primary	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		Throughout study	No
Primary	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		Through Week 48	No
Primary	Effect of peginterferon alfa-2b with or without ribavirin on liver histology		At Week 72	No

External Links

•   Click here for more information about peginterferon alfa-2
•   Click here for more information about ribavirin