Hepatitis B, HIV Infections
Conditions
Keywords
HIV-1, HBV, treatment, tenofovir, emtricitabine, Treatment Naive, HIV-1 infection, Hepatitis B virus infection
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)
Interventions
DRUGtenofovir
DRUGemtricitabine
DRUGzidovudine
DRUGefavirenz
Sponsors
Gilead Sciences
International Antiviral Therapy Evaluation Center
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| HBV DNA suppression as measured by comparison of area under the curve (AUC) measurements after 48 weeks therapy | — |
Secondary
| Measure | Time frame |
|---|---|
| Suppression of plasma HIV-RNA (< 50 copies/ml) | — |
| Changes in CD4+ /CD8+ cell counts | — |
| Rate of emergence of lamivudine (LAM)-resistant HBV genotypes | — |
| Proportion of patients with undetectable HBV DNA in serum | — |
| Rate of hepatitis B e antigen (HBeAg) and hepatitis B surface antigen (HBsAg) seroconversion | — |
| Presence of covalently closed circle DNA (cccDNA) on liver biopsy | — |
Countries
Netherlands
Outcome results
None listed