Virological and Clinical Anti-Hepatitis B Virus (HBV) Efficacy of Tenofovir and Emtricitabine in Patients With HIV/HBV co-Infection

Virological and Clinical Anti-HBV Efficacy of Tenofovir and Emtricitabine in Antiretroviral Naïve Patients With HIV/HBV co-Infection

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)

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)

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)