A Comparison of Adefovir and Tenofovir for the Treatment of Lamivudine-Resistant Hepatitis B Virus in People With HIV

• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT00033163
• Collaborator: (none)
• Enrollment: 90
• Locations: 15
• Patients Per Site: 6

Study Details

Study Description

Brief Summary

Control of hepatitis B virus (HBV) infection can be difficult in HIV infected people who have taken the antiviral lamivudine (3TC). These people may have HBV that has become resistant to 3TC. Adefovir dipivoxil (ADV) has shown promising anti-HBV activity in clinical trials; tenofovir disoproxil fumarate (TDF) is used to treat HIV and may also be effective against HBV. The purpose of this study is to find out if adding ADV or TDF to a highly active antiretroviral therapy (HAART) regimen that includes 3TC has an effect on HBV infection in patients coinfected with HIV and HBV. The tolerability and safety of these drugs will be examined.

Condition or Disease	Intervention/Treatment	Phase
HIV Infections; Hepatitis B	Drug: Adefovir dipivoxil; Drug: Tenofovir disoproxil fumarate	Phase 2

Detailed Description

HBV presents a worldwide health crisis and is difficult to treat when a patient's HBV strain is no longer responsive to 3TC. Given the significant incidence of 3TC-resistant HBV in patients receiving this drug as part of an antiretroviral regimen, other agents with anti-HBV activity are needed. ADV has shown promising anti-HBV activity in preclinical assessments and in Phase I, II, and III clinical trials. TDF, developed for the treatment of HIV infection, has in vitro activity against HBV. This study will compare TDF/3TC combination therapy with ADV/3TC combination therapy to determine which treatment regimen is more effective in patients coinfected with HBV and HIV.

This study will include two populations of patients. Patients in Population A are on stable HAART that includes TDF and will either be in Group I (compensated liver disease) or Group II (decompensated liver disease). All patients in Population A will be randomly assigned to one of two arms: Arm 1 patients will receive 10 mg ADV daily and TDF placebo; Arm 2 patients will receive ADV placebo and 300 mg TDF. Patients in Population B are on stable HAART and have never taken TDF as part of their HAART. Population B patients will receive 300 mg TDF daily during the course of the study.

Study visits will occur every 4 weeks for the 96-week study period. Targeted clinical and medication assessments and blood work assessing clotting time, liver function, and blood chemistry will be conducted at each study visit. HIV and HBV DNA viral load will be tested every 12 weeks. CD4 cell counts will be tested at Weeks 24, 48, 72, and 96.

Study Design

• Study Type: Interventional
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Primary Purpose: Treatment
• Official Title: A Randomized, Phase II, Controlled Trial Comparing the Efficacy of Adefovir Dipivoxil and Tenofovir Disoproxil Fumarate for the Treatment of Lamivudine-Resistant Hepatitis B Virus in Subjects Who Are Co-Infected With HIV
• Actual Study Completion Date: May 1, 2005

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria for All Participants:

• HIV infected

• HBV infected

• Serum HBV DNA of 100,000 copies/ml or greater

• Positive for serum hepatitis B surface antigen (HBsAg) within 12 weeks prior to study entry

• Agree to use acceptable methods of contraception

• Serum alpha-fetoprotein (AFP) of 50 ng/ml or less within 30 days of study entry. If AFP is greater than 50 ng/ml, the patient must have an imaging study of the liver showing no tumor within 30 days prior to study entry

Inclusion Criteria for Population A:

• Uninterrupted stable HAART regimen at study entry for at least 12 continuous weeks prior to study entry

• HIV viral load of 10,000 copies/ml or less within 12 weeks of study entry

Inclusion Criteria for Population A, Group I:

• Compensated liver disease

• Child-Pugh-Turcotte (CPT) score of less than 7

Exclusion Criteria for Population A, Group I:

• Excess fluid in the space between the membranes lining the abdomen and abdominal organs (ascites)

• Gastrointestinal (variceal) bleeding

• Brain and nervous system damage as a result of liver disease

• Abnormal blood clotting time

Inclusion Criteria for Population A, Group II:

• Decompensated liver disease

• CPT score of 7-12

Inclusion Criteria for Population B:

• Prior HAART regimen

• Never taken TDF as part of HAART regimen

• Serum HBV DNA of 100,000 copies/ml or greater within 12 weeks of study entry

• HIV viral load of greater than 10,000 copies/ml within 12 weeks of study entry

• CPT score less than 13

Exclusion Criteria

• Serious kidney problems within the last 12 months

• Allergic or sensitive to ADV or TDF

• Active hepatitis C virus (HCV) disease or unknown HCV status within 24 weeks of study entry

• Any medical or mental illness that, in the opinion of the investigator, would interfere with the protocol

• Past or current alcohol or drug abuse that would affect the protocol

• Malignancy that, in the opinion of the investigator, would make the patient unsuitable for the study

• Certain anti-HBV drugs within 90 days of study entry or expected use of these agents during the course of the study

• Drugs that may damage the kidneys within 8 weeks prior to study screening or expected use of these agents during the course of the study

• Systemic corticosteroids within 90 days of study entry

• Current use of drugs containing pivalic acid

• Certain investigational anti-HIV agents

• Pregnant or breastfeeding

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UC Davis Medical Center	Sacramento	California	United States	95814
2	Univ. of California Davis Med. Ctr., ACTU	Sacramento	California	United States
3	Ucsf Aids Crs	San Francisco	California	United States	94110
4	University of Colorado Hospital CRS	Aurora	Colorado	United States	80262
5	Northwestern University CRS	Chicago	Illinois	United States	60611
6	Cook County Hosp. CORE Ctr.	Chicago	Illinois	United States	60612
7	Johns Hopkins Adult AIDS CRS	Baltimore	Maryland	United States	21287
8	Beth Israel Med. Ctr., ACTU	New York	New York	United States	10003
9	NY Univ. HIV/AIDS CRS	New York	New York	United States	10016
10	Cornell CRS	New York	New York	United States	10021
11	Weill Med. College of Cornell Univ., The Cornell CTU	New York	New York	United States
12	Univ. of Cincinnati CRS	Cincinnati	Ohio	United States	452670405
13	MetroHealth CRS	Cleveland	Ohio	United States	441091998
14	Vanderbilt Therapeutics CRS	Nashville	Tennessee	United States	37203
15	University of Washington AIDS CRS	Seattle	Washington	United States	98104

Sponsors and Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID)

Investigators

• Study Chair: Bruce Polsky, MD, St. Luke's-Roosevelt Hospital Center
• Study Chair: Marion Peters, MD, University of California, San Francisco

Study Documents (Full-Text)

None provided.

More Information

Publications

• Benhamou Y, Bochet M, Thibault V, Calvez V, Fievet MH, Vig P, Gibbs CS, Brosgart C, Fry J, Namini H, Katlama C, Poynard T. Safety and efficacy of adefovir dipivoxil in patients co-infected with HIV-1 and lamivudine-resistant hepatitis B virus: an open-label pilot study. Lancet. 2001 Sep 1;358(9283):718-23.
• 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.
• Dieterich DT. HIV and hepatitis B virus: options for managing coinfection. Top HIV Med. 2003 Jan-Feb;11(1):16-9. Review.
• Rockstroh JK. Management of hepatitis B and C in HIV co-infected patients. J Acquir Immune Defic Syndr. 2003 Sep;34 Suppl 1:S59-65. Review.
• Thio CL. Hepatitis B in the human immunodeficiency virus-infected patient: epidemiology, natural history, and treatment. Semin Liver Dis. 2003 May;23(2):125-36. Review.

• Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
• ClinicalTrials.gov Identifier: NCT00033163
• Other Study ID Numbers: A5127; 10678; ACTG A5127; AACTG A5127
• First Posted: Apr 9, 2002
• Last Update Posted: Nov 1, 2021
• Last Verified: Oct 1, 2021

• Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID): Antiviral Agents; Hepatitis B; Drug Resistance, Microbial; Lamivudine; DNA, Viral; Hepatitis B Virus; Adefovir dipivoxil; Tenofovir disoproxil fumarate; Treatment Experienced
• Additional relevant MeSH terms: Hepatitis A; Hepatitis B; Hepatitis; Tenofovir; Adefovir; Adefovir dipivoxil

Study Results

No Results Posted as of Nov 1, 2021