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A Surveillance Program for the Detection of Hepatitis B Virus (HBV) Resistance to Tenofovir in HIV-HBV co-Infected Patients

The recruitment status of this study is unknown. The completion date has passed and the status has not been verified in more than two years.
Verified April 2008 by Bayside Health.
Recruitment status was:  Recruiting
Gilead Sciences
Information provided by:
Bayside Health Identifier:
First received: April 16, 2008
Last updated: NA
Last verified: April 2008
History: No changes posted
Human immunodeficiency virus/Hepatitis B virus (HIV/HBV) co-infections are frequently observed due to shared routes of transmission, with reported figures indicating 6-9% of HIV-infected individuals in developed countries are chronically infected with HBV. HIV infection impacts on the natural progression of HBV infection, increasing levels of HBV replication and the risk of liver-associated mortality. Liver diseases associated with HBV are affected by the antiviral drugs used for HIV infection (toxic side effects), the current immune function in the patient, by improvements in the immune system brought about by control of the HIV infection, and by the development of resistance to the antiviral agents used for both the hepatitis B and the HIV infection. Tenofovir (TDF) is a newer antiviral drug that is frequently used for HIV infection and is also highly active against hepatitis B; however it is still unknown whether resistance to TDF will eventually develop and how this will affect the long-term outcomes

HIV Infections
Hepatitis B Virus

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: A Surveillance Program for the Detection of Hepatitis B Virus (HBV) Resistance to Tenofovir (TDF) in HIV-HBV co-Infected Patients

Resource links provided by NLM:

Further study details as provided by Bayside Health:

Biospecimen Retention:   Samples Without DNA
Stored serum samples

Estimated Enrollment: 92
Study Start Date: April 2008
Estimated Study Completion Date: September 2010
Estimated Primary Completion Date: April 2010 (Final data collection date for primary outcome measure)
individuals co-infected with HIV-HBV and receiving tenofovir as aprt of their HAART regimen

Detailed Description:

Tenofovir disoproxil fumarate (TDF) is a nucleotide analogue that can inhibit both HIV and HBV DNA polymerases, and is active against wild-type HBV and HBV strains that contain lamivudine-associated polymerase gene mutations (Dore, Cooper et al. 2004). TDF was approved for use, in combination with other antiretrovirals, for HIV therapy in April 2002 in Australia. It is not currently approved for use in Australia for treatment of HBV mono-infection. TDF has only recently become available in Thailand where HIV/HBV co-infected individuals are predominantly infected with genotype B and C. In contrast, in Australia and Europe, the dominant HBV genotype in HIV/HBV co-infected individuals is A and D. As with all antiviral agents there is concern with long-term use and the development of resistance.

There has been a report of a signature mutation leading to TDF resistance at rtA194T (Sheldon et al., 2005). We recently conducted a retrospective study of HIV/HBV co infected individuals in Melbourne who had received TDF for at least 3 months. Twenty-eight patients had samples available on TDF of which four (~14%) had detectable HBV DNA by PCR. We did not identify the mutation rtA194T or rtV214A/Q215S in individuals failing TDF and found that the only persisting mutations were LMV-resistant mutations. These findings highlight the need for a surveillance system for HIV-HBV co-infected individuals receiving TDF for the detection of novel mutations in the four major HBV genotypes. In addition, it is important to determine the clinical and virological risk factors for TDF failure. This is particularly important given that these agents will be used indefinitely in this patient population and with the development of unique drug resistant mutations there will be implications for progression of liver disease and future therapeutic choices.

This study will recruit patients who are co-infected with HIV and HBV, and are currently taking or who are about to commence the anti-HIV drug TDF. The study cohort will include HIV-HBV co-infected individuals from the Alfred Hospital and Melbourne Sexual Health Clinic. Other sites, not covered by this application, are St Vincent's Hospital, Sydney and King Chulalongkorn Memorial Hospital, Bangkok, Thailand.

The aim of the study is to identify any changes in the HBV DNA that might be associated with resistance to TDF, to determine how long any changes take to occur and to determine the effect of these changes on the clinical response to TDF.

This will be achieved by 6 monthly assessment over a 2 year period, with medical history, physical examination, routine clinical investigations, hepatitis B activity and HBV DNA sequencing.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Individuals co-infected with HIV-HBV and currently receiving tenofovir as part of their HAART regimen

Inclusion Criteria:

  • 18 years of age and older
  • HIV positive
  • 2 positive Hepatitis B surface antigen results at least 6 months apart
  • currently receiving (or about to commence) tenofovir therapy

Exclusion Criteria:

  • unable to provide informed consent
  • lack of a serum sample prior to commencing tenofovir
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT00660361

Contact: Jennifer Audsley, PhD 613-9903-0184

Australia, Victoria
The Alfred Hospital Recruiting
Melbourne, Victoria, Australia, 3004
Contact: Jennifer Audsley, PhD    613-9903-0184   
Sub-Investigator: Jennifer Hoy         
Principal Investigator: Joe Sasadeusz         
Sub-Investigator: David Iser         
Sponsors and Collaborators
Bayside Health
Gilead Sciences
Principal Investigator: Sharon L, MD, PhD The Alfred Hospital and Monash University
  More Information

Responsible Party: Professor Sharon Lewin, The Alfred Hospital and Monash University Identifier: NCT00660361     History of Changes
Other Study ID Numbers: ALF-50/08
Study First Received: April 16, 2008
Last Updated: April 16, 2008

Keywords provided by Bayside Health:
drug resistance
HIV-HBV co-infection

Additional relevant MeSH terms:
Hepatitis A
HIV Infections
Hepatitis B
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Lentivirus Infections
Retroviridae Infections
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Hepadnaviridae Infections
DNA Virus Infections
Antiviral Agents
Anti-Infective Agents
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Retroviral Agents
Anti-HIV Agents processed this record on April 21, 2017