Treatment of Hepatitis B Virus (HBV) Before Beginning Anti-HIV Drugs in Patients With Both HBV and HIV

• ClinicalTrials.gov Identifier: NCT00051090
• Recruitment Status: Withdrawn
• First Posted: January 6, 2003
• Last Update Posted: November 1, 2021
• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Information provided by (Responsible Party): National Institute of Allergy and Infectious Diseases (NIAID)

Tracking Information

• First Submitted Date: January 3, 2003
• First Posted Date: January 6, 2003
• Last Update Posted Date: November 1, 2021
• Study Start Date: Not Provided
• Primary Completion Date: Not Provided

Current Primary Outcome Measures (submitted: September 25, 2008)

• HBV viral loads [ Time Frame: At Study entry, Week 24 and Week 48 ]
• Safety and tolerability of telbivudine [ Time Frame: Throughout study ]

• Original Primary Outcome Measures: Not Provided

Current Secondary Outcome Measures (submitted: September 25, 2008)

• Safety and tolerability of HAART [ Time Frame: Throughout study ]
• Change in ALT level [ Time Frame: Throughout study ]
• HBV genetic mutation status at HBV virologic failure [ Time Frame: Throughout study ]
• HIV viral load [ Time Frame: At Study entry, Weeks 24, 48, and 60 ]
• HBV viral load and hepatic transaminase concentrations [ Time Frame: At Week 60 ]

• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Treatment of Hepatitis B Virus (HBV) Before Beginning Anti-HIV Drugs in Patients With Both HBV and HIV
• Official Title: Multicenter, Pilot Study of Telbivudine (LdT) Anti-HBV Treatment Prior to the Initiation of Highly Active Antiretroviral Therapy Containing Lamivudine in Subjects Coinfected With HBV and HIV
• Brief Summary: This study will evaluate the drug telbivudine (LdT) for treatment of hepatitis B virus (HBV) in HIV infected patients. Patients will take telbivudine alone for 24 weeks, add anti-HIV drugs for 24 weeks, then stop taking telbivudine while continuing their anti-HIV drug regimen. To enroll in this study, patients must not be taking any anti-HIV drugs and cannot have taken more than 31 days of treatment with lamivudine (3TC), protease inhibitors (PIs), or nonnucleoside reverse transcriptase inhibitors (NNRTIs).

Detailed Description

Studies indicate that 70% to 80% of HIV infected patients have or have had HBV infection and that 10% are HBV carriers. Lamivudine therapy for treatment of HBV in HIV infected patients has limited long-term efficacy due to the development of resistance mutations. Telbivudine is a thymidine analogue with excellent HBV inhibitory activity but no anti-HIV activity. The primary objective of this study is to evaluate the safety and anti-HBV activity of telbivudine alone and in combination with a lamivudine-based highly active antiretroviral therapy (HAART) regimen in patients coinfected with HBV and HIV.

Patients in this study will take telbivudine for 24 weeks. At Week 24, patients will add a HAART regimen containing lamivudine and efavirenz plus either didanosine or abacavir. Patients who are unable to add a HAART regimen at Week 24 due to lab abnormalities or other contraindications will be allowed to delay the initiation of HAART until Week 30. Patients may initiate HAART prior to Week 24 if deemed medically necessary by the primary HIV care provider. Patients will take both telbivudine and HAART for 24 weeks. At Week 48, patients will discontinue telbivudine and continue on the HAART regimen alone for an additional 12 weeks.

• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: Non-Randomized; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• HIV Infections
• Hepatitis B

Intervention

• Drug: Telbivudine
  Administered orally at a daily dosage of 600 mg for a period of 48 weeks
• Drug: Lamivudine
  Administered orally at a total daily dosage of 300 mg for Weeks 24-48
• Drug: Efavirenz
  Administered orally at a daily dose of 600 mg
• Drug: Didanosine
  Administered orally at a total dosage of either 400 mg or 250 mg determined by individual weight
• Drug: Abacavir
  Administered orally twice daily in doses of 300 mg

Study Arms

Experimental: A

All eligible study participants

Interventions:

• Drug: Telbivudine
• Drug: Lamivudine
• Drug: Efavirenz
• Drug: Didanosine
• Drug: Abacavir

Publications *

• den Brinker M, Wit FW, Wertheim-van Dillen PM, Jurriaans S, Weel J, van Leeuwen R, Pakker NG, Reiss P, Danner SA, Weverling GJ, Lange JM. Hepatitis B and C virus co-infection and the risk for hepatotoxicity of highly active antiretroviral therapy in HIV-1 infection. AIDS. 2000 Dec 22;14(18):2895-902. doi: 10.1097/00002030-200012220-00011.
• Sulkowski MS, Thomas DL, Chaisson RE, Moore RD. Hepatotoxicity associated with antiretroviral therapy in adults infected with human immunodeficiency virus and the role of hepatitis C or B virus infection. JAMA. 2000 Jan 5;283(1):74-80. doi: 10.1001/jama.283.1.74.
• Sulkowski MS, Thomas DL, Mehta SH, Chaisson RE, Moore RD. Hepatotoxicity associated with nevirapine or efavirenz-containing antiretroviral therapy: role of hepatitis C and B infections. Hepatology. 2002 Jan;35(1):182-9. doi: 10.1053/jhep.2002.30319.
• Benhamou Y, Bochet M, Thibault V, Di Martino V, Caumes E, Bricaire F, Opolon P, Katlama C, Poynard T. Long-term incidence of hepatitis B virus resistance to lamivudine in human immunodeficiency virus-infected patients. Hepatology. 1999 Nov;30(5):1302-6. doi: 10.1002/hep.510300525.

Recruitment Information

• Recruitment Status: Withdrawn
• Actual Enrollment (submitted: April 6, 2012): 0
• Original Enrollment (submitted: June 23, 2005): 36
• Study Completion Date: Not Provided
• Primary Completion Date: Not Provided

Eligibility Criteria

Inclusion Criteria:

• HIV positive
• No antiretroviral therapy within 6 months prior to study entry
• Less than 31 days cumulative therapy with lamivudine, a protease inhibitor, or a nonnucleoside reverse transcriptase inhibitor
• Willingness to delay HAART until at least Week 24 of study
• Ability to procure and initiate HAART regimen
• CD4+ cell count >= 250 cells/mm3 within 60 days prior to study entry
• HIV-1 RNA > 400 copies/ml within 60 days prior to study entry
• Serum HBV DNA >= 1,000,000 copies/ml within 60 days prior to study entry
• Positive serum hepatitis B surface antigen (HbsAG)
• Acceptable methods of contraception

Exclusion Criteria:

• Pregnancy or breast-feeding
• Allergy, sensitivity, or intolerance to study drugs
• Alcohol consumption averaging more than 1 drink/day within past 30 days
• Decompensated cirrhosis
• HCV antibody positive or known HCV RNA positive
• HDV antibody positive
• Certain medical conditions
• Use of certain medications with anti-HBV activity within 90 days of study entry
• Use of systemic corticosteroids within 30 days of study entry
• Use of any systemic antineoplastic, immunomodulatory treatment, or radiation within 24 weeks of study entry

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Not Provided
• Removed Location Countries: United States

Administrative Information

• NCT Number: NCT00051090
• Other Study ID Numbers: A5167; 10962 ( Registry Identifier: DAIDS ES ); ACTG A5167
• Has Data Monitoring Committee: Not Provided
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
• Original Responsible Party: Not Provided
• Current Study Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Chair: Patrick Lynch, M.D.; Northwestern University

• PRS Account: National Institute of Allergy and Infectious Diseases (NIAID)
• Verification Date: October 2021