Hepatitis B Virus, HIV Infections
Conditions
Keywords
TDF+FTC, FTC, HIV/HBV, TDF compared to TDF+FTC in HIV/HBV, Treatment Naive
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.
Interventions
DRUGEmtricitabine
Emtricitabine 200 mg OD + Zidovudine 300 mg BID + EFV OD compared to TDF + FTC + EFV
Sponsors
Gilead Sciences
Ministry of Health, Thailand
The HIV Netherlands Australia Thailand Research Collaboration
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| HBV DNA suppression to levels below the limit of detection (<400 copies/ml) | week 48 |
Secondary
| Measure | Time frame |
|---|---|
| Proportion of patients with undetectable HBV DNA in serum at 12 and 24 weeks | 12 and 24 weeks |
| Rate of HBeAg and HBsAg seroconversion at 12, 24 and 48 weeks. | 12, 24 and 48 weeks |
| Rate of emergence of LAM-resistant HBV genotypes at 48 weeks. | 48 weeks |
| Rate of hepatic cytolysis (ALT level > 5x ULN). | 48 weeks |
| HBV suppression as measured by comparison of AUC measurements at 12 and 24 weeks | 12 and 24 weeks |
| Suppression of plasma HIV-RNA (< 50 copies/ml) through 48 weeks. | 48 weeks |
| Changes in CD4+ /CD8+ cell counts through 48 weeks | 48 weeks |
| Toxicity | 48 weeks |
| Assessment of effect of therapy on histological changes in the liver and effect on ccc-HBV-DNA | 48 weeks |
| Change from baseline in ALT levels and time to ALT normalization. | 48 weeks |
Countries
Thailand
Outcome results
None listed