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

Sponsor:	National Institute of Allergy and Infectious Diseases (NIAID)
Information provided by:	National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:	NCT00033163

Purpose

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	Intervention	Phase
HIV Infections Hepatitis B	Drug: Adefovir dipivoxil Drug: Tenofovir disoproxil fumarate	Phase II

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study 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

Resource links provided by NLM:

Genetics Home Reference related topics: complement factor I deficiency

MedlinePlus related topics: HIV/AIDS Hepatitis Hepatitis A Hepatitis B

Drug Information available for: Adefovir Lamivudine Adefovir dipivoxil Tenofovir Tenofovir disoproxil Tenofovir Disoproxil Fumarate Recombinant hepatitis B vaccine Hepatitis B Vaccines Hepatitis A Vaccines

U.S. FDA Resources

Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Estimated Enrollment:	53
Primary Completion Date:	May 2005 (Final data collection date for primary outcome measure)

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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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

Please refer to this study by its ClinicalTrials.gov identifier: NCT00033163

Locations

United States, California
UC Davis Med Ctr, CARES Clinic
Sacramento, California, United States, 95814
University of California San Diego Antiviral Research Ctr
San Diego, California, United States, 92103
Univ of California San Francisco
San Francisco, California, United States, 94110
United States, Colorado
Univ of Colorado Health Sciences Ctr
Denver, Colorado, United States, 80262
United States, Hawaii
Univ of Hawaii
Honolulu, Hawaii, United States, 96816
United States, Illinois
Northwestern Univ Med School
Chicago, Illinois, United States, 60611
The Core Ctr
Chicago, Illinois, United States, 60612
Cook County Hospital Core Center
Chicago, Illinois, United States, 60612
United States, Maryland
Johns Hopkins Hosp
Baltimore, Maryland, United States, 21287
United States, Massachusetts
Beth Israel Deaconess - West Campus
Boston, Massachusetts, United States, 02215
United States, New York
Mount Sinai Med Ctr
New York, New York, United States, 10029
Beth Israel Med Ctr
New York, New York, United States, 10003
NYU/Bellevue
New York, New York, United States, 10016
The Cornell Clinical Trials Unit
New York, New York, United States, 10021
Chelsea Clinic
New York, New York, United States, 10011
United States, North Carolina
Univ of North Carolina
Chapel Hill, North Carolina, United States, 275997215
United States, Ohio
Univ of Cincinnati
Cincinnati, Ohio, United States, 452670405
MetroHealth Med Ctr
Cleveland, Ohio, United States, 441091998
United States, Tennessee
Comprehensive Care Clinic
Nashville, Tennessee, United States, 37203
United States, Texas
Univ of Texas, Southwestern Med Ctr
Dallas, Texas, United States, 75390
Univ of Texas Galveston
Galveston, Texas, United States, 775550435
United States, Washington
Univ of Washington (Seattle)
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

More Information

Additional Information:

Click here for more information about tenofovir disoproxil fumarate This link exits the ClinicalTrials.gov site

Haga clic aquí para ver información sobre este ensayo clínico en español. This link exits the ClinicalTrials.gov site

Publications:

Peters MG, Andersen J, Lynch P, Liu T, Alston-Smith B, Brosgart CL, Jacobson JM, Johnson VA, Pollard RB, Rooney JF, Sherman KE, Swindells S, Polsky B; ACTG Protocol A5127 Team. Randomized controlled study of tenofovir and adefovir in chronic hepatitis B virus and HIV infection: ACTG A5127. Hepatology. 2006 Nov;44(5):1110-6.

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.

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.

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.

ClinicalTrials.gov Identifier:	NCT00033163 History of Changes
Other Study ID Numbers:	ACTG A5127, AACTG A5127, DAIDS-ES ID 10678
Study First Received:	April 8, 2002
Last Updated:	February 25, 2011
Health Authority:	United States: Food and Drug Administration

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:

HIV Infections
Acquired Immunodeficiency Syndrome
Hepatitis
Hepatitis A
Hepatitis B
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Liver Diseases

Digestive System Diseases
Hepatitis, Viral, Human
Enterovirus Infections
Picornaviridae Infections
Hepadnaviridae Infections
DNA Virus Infections
Adefovir dipivoxil
Adefovir
Lamivudine
Tenofovir disoproxil
Tenofovir
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on February 09, 2012