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

HIV Infections Clinical Trial

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT00051090
• Other study ID #: A5167
• Secondary ID: 10962ACTG A5167
• Status: Withdrawn
• Phase: N/A

Study information

• Verified date: October 2021
• Source: National Institute of Allergy and Infectious Diseases (NIAID)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Hepatitis
• Hepatitis A
• Hepatitis B
• HIV Infections

Intervention

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

Locations

Country	Name	City	State
n/a

Sponsors (1)

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

References & Publications (4)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	HBV viral loads		At Study entry, Week 24 and Week 48
Primary	Safety and tolerability of telbivudine		Throughout study
Secondary	Safety and tolerability of HAART		Throughout study
Secondary	Change in ALT level		Throughout study
Secondary	HBV genetic mutation status at HBV virologic failure		Throughout study
Secondary	HIV viral load		At Study entry, Weeks 24, 48, and 60
Secondary	HBV viral load and hepatic transaminase concentrations		At Week 60

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