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

NCT00033163 | Completed Phase 2

• 4 other identifiers: A512710678ACTG A5127AACTG A5127
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 15

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.

Conditions

HIV Infections; Hepatitis B

Keywords

Antiviral Agents; Hepatitis B; Drug Resistance, Microbial; Lamivudine; DNA, Viral; Hepatitis B Virus; Adefovir dipivoxil; Tenofovir disoproxil fumarate; Treatment Experienced

Interventions

Adefovir dipivoxil DRUG

Tenofovir disoproxil fumarate DRUG

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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
• Decompensated liver disease
• CPT score of 7-12
• 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
• 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

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (15)

UC Davis Medical Center

Sacramento, California, 95814, United States

Location

Univ. of California Davis Med. Ctr., ACTU

Sacramento, California, United States

Location

Ucsf Aids Crs

San Francisco, California, 94110, United States

Location

University of Colorado Hospital CRS

Aurora, Colorado, 80262, United States

Location

Northwestern University CRS

Chicago, Illinois, 60611, United States

Location

Cook County Hosp. CORE Ctr.

Chicago, Illinois, 60612, United States

Location

Johns Hopkins Adult AIDS CRS

Baltimore, Maryland, 21287, United States

Location

Beth Israel Med. Ctr., ACTU

New York, New York, 10003, United States

Location

NY Univ. HIV/AIDS CRS

New York, New York, 10016, United States

Location

Cornell CRS

New York, New York, 10021, United States

Location

Weill Med. College of Cornell Univ., The Cornell CTU

New York, New York, United States

Location

Univ. of Cincinnati CRS

Cincinnati, Ohio, 452670405, United States

Location

MetroHealth CRS

Cleveland, Ohio, 441091998, United States

Location

Vanderbilt Therapeutics CRS

Nashville, Tennessee, 37203, United States

Location

University of Washington AIDS CRS

Seattle, Washington, 98104, United States

Location

Related Publications (7)

• 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.

  PMID: 10534354 BACKGROUND

• 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. doi: 10.1016/s0140-6736(01)05840-8.

  PMID: 11551579 BACKGROUND

• Dieterich DT. HIV and hepatitis B virus: options for managing coinfection. Top HIV Med. 2003 Jan-Feb;11(1):16-9.

  PMID: 12717046 BACKGROUND

• 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. doi: 10.1097/00126334-200309011-00009.

  PMID: 14562859 BACKGROUND

• 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. doi: 10.1055/s-2003-39951.

  PMID: 12800066 BACKGROUND

• 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. doi: 10.1002/hep.21388.

  PMID: 17058225 RESULT

• Johnson VA, Cramer YS, Rosenkranz SL, Becker S, Klingman KL, Kallungal B, Coakley E, Acosta EP, Calandra G, Saag MS; NIH/NIAID AIDS Clinical Trials Group A5210 Protocol Team. Antiretroviral Activity of AMD11070 (An Orally Administered CXCR4 Entry Inhibitor): Results of NIH/NIAID AIDS Clinical Trials Group Protocol A5210. AIDS Res Hum Retroviruses. 2019 Aug;35(8):691-697. doi: 10.1089/AID.2018.0256. Epub 2019 Jun 18.

  PMID: 31099252 DERIVED

MeSH Terms

Conditions

HIV Infections; Hepatitis B

Interventions

adefovir dipivoxil; Tenofovir

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Hepadnaviridae Infections; DNA Virus Infections; Hepatitis, Viral, Human; Hepatitis; Liver Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Bruce Polsky, MD

  St. Luke's-Roosevelt Hospital Center

  STUDY CHAIR

• Marion Peters, MD

  University of California, San Francisco

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 8, 2002
• First Posted: April 9, 2002
• Study Completion: May 1, 2005
• Last Updated: November 1, 2021

Record last verified: 2021-10

Locations

US (15)