Clinical trial NCT00476463: Efficacy of Tenofovir and Emtricitabine in ARV-naive Patients With HIV/HBV Co-infection
Official title: Virological and Clinical Anti-HBV Efficacy of Tenofovir and Emtricitabine in Antiretroviral Naive Patients With HIV/HBV Co-infection
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hepatitis B Virus
HIV Infections
Keywords: TDF+FTC
FTC
HIV/HBV
TDF compared to TDF+FTC in HIV/HBV
Treatment Naive
Lead sponsor: The HIV Netherlands Australia Thailand Research Collaboration
Sponsor class: OTHER
Collaborators: name: Gilead Sciences
name: Ministry of Health, Thailand
First posted: 2007-05-22
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Combination therapy with anti-HBV activity may both increase HBV suppression rates and reduce emergence of resistant strains. Several new therapeutic agents are currently in development, however combination therapy trials in the HBV-infected population have only recently commenced. No such trials have been undertaken in the HIV/HBV co-infected population.

Detailed description: The primary study objective is to compare HBV DNA suppression to levels below the limit of detection (\<400 copies/ml) by week 48 in each treatment group. Virological and clinical anti-HBV efficacy of tenofovir and emtricitabine in antiretroviral naive patients with HIV/HBV co-infection.

Eligibility criteria: Inclusion Criteria:

* Written informed consent
* Documented HIV infection (positive serology for HIV-1 and detectable HIV-1 RNA)
* Age 18 - 70 years
* HBV DNA \> 106 copies/ml
* HBsAg positive for \> 6 months

In case documented duration of HBsAg seropositive is less than 6 months (this situation is most likely to occur in patients newly presenting to the HIV-outpatient clinic) the patient is eligible if the patient is:

1. HBsAg positive and
2. HBc core IgM antibody negative and
3. the liver biopsy gives evidence for a chronic active hepatitis. Thus making it likely that this patient has acquired the HBV infection more than 6 months ago.

   * ALT \< 10 x ULN
   * Creatinine \<= 2.0mg/dl
   * Platelet count \>= 50,000/mm3
   * HIV-1 therapy naive
   * No prior exposure to anti-HBV agents (LAM, adefovir, TDF) although prior IFN treatment allowed

Exclusion Criteria:

* HCV-RNA positive or Anti-HAV IgM positive
* Acute hepatitis (serum ALT \> 1000 U/L)
* Prior LAM, TDF, or ADV therapy
* Active opportunistic infection
* Other causes of chronic liver disease identified ( autoimmune hepatitis, haemochromatosis, Wilsons disease, alfa-1-antitrypsin deficiency)
* Concurrent malignancy requiring cytotoxic chemotherapy
* Decompensated or Child's C cirrhosis
* Alfa-fetoprotein (AFP) \> 3X ULN (unless negative CT scan or MRI within 3 months of entry date)
* Pregnancy or lactation
* Any other condition which in the opinion of the investigator might interfere with compliance or outcome of the study

Primary outcomes:
measure: HBV DNA suppression to levels below the limit of detection (<400 copies/ml)
timeFrame: week 48
Secondary outcomes:
measure: HBV suppression as measured by comparison of AUC measurements at 12 and 24 weeks
timeFrame: 12 and 24 weeks
measure: Proportion of patients with undetectable HBV DNA in serum at 12 and 24 weeks
timeFrame: 12 and 24 weeks
measure: Rate of HBeAg and HBsAg seroconversion at 12, 24 and 48 weeks.
timeFrame: 12, 24 and 48 weeks
measure: Rate of emergence of LAM-resistant HBV genotypes at 48 weeks.
timeFrame: 48 weeks
measure: Rate of hepatic cytolysis (ALT level > 5x ULN).
timeFrame: 48 weeks
measure: Change from baseline in ALT levels and time to ALT normalization.
timeFrame: 48 weeks
measure: Suppression of plasma HIV-RNA (< 50 copies/ml) through 48 weeks.
timeFrame: 48 weeks
measure: Changes in CD4+ /CD8+ cell counts through 48 weeks
timeFrame: 48 weeks
measure: Toxicity
timeFrame: 48 weeks
measure: Assessment of effect of therapy on histological changes in the liver and effect on ccc-HBV-DNA
timeFrame: 48 weeks
Other outcomes:
Locations:
city: Bangkok
country: Thailand
facility: HIV-NAT Thai Red Cross AIDS Research Center
Study officials:
affiliation: HIV-NAT Thai Red Cross AIDS Research Center
name: Kiat Ruxrungtham, MD
role: PRINCIPAL_INVESTIGATOR
References: