Clinical trial NCT00127959: Virological and Clinical Anti-Hepatitis B Virus (HBV) Efficacy of Tenofovir and Emtricitabine in Patients With HIV/HBV co-Infection
Official title: Virological and Clinical Anti-HBV Efficacy of Tenofovir and Emtricitabine in Antiretroviral Naïve Patients With HIV/HBV co-Infection
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: HIV Infections
Hepatitis B
Keywords: HIV-1
HBV
treatment
tenofovir
emtricitabine
Treatment Naive
HIV-1 infection
Hepatitis B virus infection
Lead sponsor: International Antiviral Therapy Evaluation Center
Sponsor class: OTHER
Collaborators: name: Gilead Sciences
First posted: 2005-08-09
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a randomized multicentre trial of emtricitabine (FTC) versus tenofovir (TDF)/FTC in antiretroviral naive subjects with HIV/HBV co-infection over 48 weeks (Clinical Trial A).

Plus, a 12 week viral kinetic substudy comparing a subgroup of patients on Clinical Trial A is being conducted. (Substudy A1)

Detailed description: This is a randomized multicentre trial of FTC vs TDF/FTC in antiretroviral naive subjects with HIV/HBV co-infection over 48 weeks (Clinical Trial A).

Plus, a 12 week viral kinetic substudy comparing a subgroup of patients on Clinical Trial A is being conducted. (Substudy A1)

Primary Objectives:

* To compare the proportion of subjects with HBV DNA levels below the limit of detection (\<400 copies/ml) by week 48 in each treatment group

Secondary Objectives:

* To evaluate the emergence of HBV resistance at 48 weeks
* To compare the proportion of patients with undetectable HBV DNA at weeks 12 and 24 in each treatment group
* To compare the proportion of patients who achieve HBeAg and HBsAg seroconversion at weeks 12, 24 and 48 during the study
* To compare changes in ALT from baseline and the rate of hepatic cytolysis (ALT\>5x ULN)
* To compare suppression of HIV-1 RNA and changes in CD4/CD8 counts over 48 weeks
* To compare the effect of therapy on histological changes in the liver and the presence of ccc-DNA

Enrollment:

* 24 patients in Clinical trial A (of whom 16 enter substudy A1).

Clinical Trial A:

* Patients with HIV/HBV co-infection who are naive to HIV/HBV therapy, have detectable HBV viraemia and are willing to start antiretroviral therapy.

Inclusion Criteria:

* Written informed consent
* Documented HIV infection
* Age 18 - 70 years
* HBV DNA \> 106 copies/ml

Randomization:

* Arm 1: Zidovudine (AZT), emtricitabine (FTC), efavirenz (EFV)
* Arm 2: Tenofovir (TDF), emtricitabine (FTC), efavirenz (EFV)

Eligibility criteria: Inclusion Criteria:

* Written informed consent
* Documented HIV infection
* Age 18 - 70 years
* HBV DNA \> 10E6 copies/ml
* ALT \< 10 x ULN (upper limit of normal)
* Creatinine \<= 2.0mg/dl
* Platelet count \>= 50,000/mm3
* HIV-1 therapy naive
* No prior exposure to anti-HBV agents

Exclusion Criteria:

* Hepatitis C viral RNA (CV-RNA) positive or Anti-hepatitis A virus immunoglobulin M (HAV IgM) positive
* Acute hepatitis (serum ALT \> 1000 U/L)
* Prior LAM, TDF, or adefovir dipivoxil (ADV) therapy
* Active opportunistic infection
* Pregnancy or lactation
* Other chronic liver disease
* Concurrent malignancy requiring cytotoxic chemotherapy
* Decompensated or Child's C cirrhosis
* Alfa-fetoprotein (AFP) \> 3X ULN (unless negative computed tomography \[CT\] scan or magnetic resonance imaging \[MRI\] within 3 months of entry date)

Primary outcomes:
measure: HBV DNA suppression as measured by comparison of area under the curve (AUC) measurements after 48 weeks therapy
Secondary outcomes:
measure: Proportion of patients with undetectable HBV DNA in serum
measure: Rate of hepatitis B e antigen (HBeAg) and hepatitis B surface antigen (HBsAg) seroconversion
measure: Rate of emergence of lamivudine (LAM)-resistant HBV genotypes
measure: Suppression of plasma HIV-RNA (< 50 copies/ml)
measure: Changes in CD4+ /CD8+ cell counts
measure: Presence of covalently closed circle DNA (cccDNA) on liver biopsy
Other outcomes:
Locations:
city: Amsterdam
country: Netherlands
facility: Academic Medical Center
state: NH
Study officials:
affiliation: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
name: Joep M.A. Lange, MD PhD
role: STUDY_CHAIR
affiliation: HIVNAT Bangkok
name: Kiat Ruxrungtham, MD PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
name: Jan Prins, MD PhD
role: PRINCIPAL_INVESTIGATOR
References: