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

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

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).

Study Overview

• Status: Withdrawn
• Conditions: HIV Infections; Hepatitis B
• Intervention / Treatment: Drug: Telbivudine; Drug: Lamivudine; Drug: Efavirenz; Drug: Didanosine; Drug: Abacavir

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
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: A; All eligible study participants

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
HBV viral loads	At Study entry, Week 24 and Week 48
Safety and tolerability of telbivudine	Throughout study

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Investigators: Study Chair: Patrick Lynch, M.D., Northwestern University

Publications and helpful links

General Publications

• 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.
• 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.
• 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, 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.

Study record dates

Study Registration Dates

• First Submitted: January 3, 2003
• First Submitted That Met QC Criteria: January 3, 2003
• First Posted (Estimate): January 6, 2003

Study Record Updates

• Last Update Posted (Actual): November 1, 2021
• Last Update Submitted That Met QC Criteria: October 28, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Keywords: Drug Therapy, Combination; Reverse Transcriptase Inhibitors; Lamivudine; Antiviral Agents; Hepatitis B; Treatment Naive; HIV Infections; Antiretroviral Therapy, Highly-Active
• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; Liver Diseases; Hepatitis, Viral, Human; Hepadnaviridae Infections; DNA Virus Infections; Enterovirus Infections; Picornaviridae Infections; HIV Infections; Hepatitis B; Hepatitis; Hepatitis A; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Antimetabolites; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 Enzyme Inducers; Cytochrome P-450 CYP3A Inducers; Cytochrome P-450 CYP2B6 Inducers; Cytochrome P-450 CYP2C9 Inhibitors; Cytochrome P-450 CYP2C19 Inhibitors; Lamivudine; Didanosine; Telbivudine; Efavirenz; Abacavir
• Other Study ID Numbers: A5167; 10962 (Registry Identifier: DAIDS ES); ACTG A5167