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

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ClinicalTrials.gov Identifier: NCT00660361
Recruitment Status : Unknown
Verified April 2008 by Bayside Health.
Recruitment status was:  Recruiting
First Posted : April 17, 2008
Last Update Posted : April 17, 2008
Sponsor:
Collaborator:
Gilead Sciences
Information provided by:
Bayside Health

Tracking Information
First Submitted Date April 16, 2008
First Posted Date April 17, 2008
Last Update Posted Date April 17, 2008
Study Start Date April 2008
Estimated Primary Completion Date April 2010   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures Not Provided
Original Primary Outcome Measures Not Provided
Change History No Changes Posted
Current Secondary Outcome Measures Not Provided
Original Secondary Outcome Measures Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title A Surveillance Program for the Detection of Hepatitis B Virus (HBV) Resistance to Tenofovir in HIV-HBV co-Infected Patients
Official Title A Surveillance Program for the Detection of Hepatitis B Virus (HBV) Resistance to Tenofovir (TDF) in HIV-HBV co-Infected Patients
Brief Summary 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
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.

Study Type Observational
Study Design Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration Not Provided
Biospecimen Retention:   Samples Without DNA
Description:
Stored serum samples
Sampling Method Non-Probability Sample
Study Population Individuals co-infected with HIV-HBV and currently receiving tenofovir as part of their HAART regimen
Condition
  • HIV Infections
  • Hepatitis B Virus
Intervention Not Provided
Study Groups/Cohorts A
individuals co-infected with HIV-HBV and receiving tenofovir as aprt of their HAART regimen
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Unknown status
Estimated Enrollment
 (submitted: April¬†16,¬†2008)
92
Original Estimated Enrollment Same as current
Estimated Study Completion Date September 2010
Estimated Primary Completion Date April 2010   (Final data collection date for primary outcome measure)
Eligibility Criteria

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
Sex/Gender
Sexes Eligible for Study: All
Ages 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers No
Contacts Contact information is only displayed when the study is recruiting subjects
Listed Location Countries Australia
Removed Location Countries  
 
Administrative Information
NCT Number NCT00660361
Other Study ID Numbers ALF-50/08
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement Not Provided
Responsible Party Professor Sharon Lewin, The Alfred Hospital and Monash University
Study Sponsor Bayside Health
Collaborators Gilead Sciences
Investigators
Principal Investigator: Sharon L, MD, PhD The Alfred Hospital and Monash University
PRS Account Bayside Health
Verification Date April 2008