Efficacy and Safety of PegIFN +/- FTC / TDF to Treat Chronic Hepatitis B in HIV-Coinfected Patients
The efficacy of pegylated interferons in the treatment of chronic hepatitis B has shown superior results to standard of care in patients only infected with hepatitis B. The efficacy of pegylated interferon for the treatment of chronic hepatitis B in HIV-coinfected patients is not known at present.
The purpose of this study is to evaluate the efficacy of pegylated interferon in the treatment of chronic hepatitis B in HIV-infected individuals.
Apart from evaluating the efficacy of pegylated interferon therapy in this setting as such, i.e. in patients without present or future need of highly active antiretroviral therapy (HAART) for HIV-infection, there is a second purpose of this study, to investigate whether combination treatment of HBV-infection may be superior to pegylated interferon therapy alone.
Therefore patients without need of HAART are offered pegylated interferon alfa-2a over 48 weeks. Patients who require HAART are offered emtricitabine / tenofovir DF containing HAART over 72 weeks PLUS pegylated interferon alfa-2a over 48 weeks vs. emtricitabine / tenofovir DF containing HAART over 72 weeks WITHOUT pegylated interferon-alfa-2a.
Chronic Hepatitis B
Drug: pegylated interferon alfa-2a
Drug: tenofovir DF / emtricitabine combination therapy
Drug: pegIFN / TDF / FTC combination therapy
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Factorial Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Pegylated Interferon Alfa-2a Versus Emtricitabine / Tenofovir +/- Pegylated Interferon Alfa-2a for the Treatment of Chronic HBe-Ag Positive Hepatitis B Infection in HIV-Coinfected Patients - the PEGPLUS Trial|
- Efficacy: HBeAg seroconversion (HBeAg loss and presence of anti HBe) ; intent to treat analysis. [ Time Frame: week 48 and 72 ] [ Designated as safety issue: No ]
- Safety: study discontinuation due to adverse events; intent to treat analysis. [ Time Frame: week 48 ] [ Designated as safety issue: Yes ]
- Efficacy: loss of HBe-Ag,HBV-DNA < 5x10³ copies/ml(COBAS TaqMan HBV Test),decrease of HBV-DNA > 2xlog10 compared to baseline [ Time Frame: week 48 and 72 ] [ Designated as safety issue: No ]
- normalization of ALT,intent to treat and as treated analysis; Viral kinetics of HBV-DNA; Paired liver biopsy comparison according to METAVIR-activity and fibrosis score. [ Time Frame: week 48 and 72 ] [ Designated as safety issue: No ]
- for Arm B (B1 and B2): HIV-RNA < 50 copies/ml and CD4-cell increase intent to treat and as treated analysis [ Time Frame: Weeks 4, 12, 24, 48 and 72 ] [ Designated as safety issue: No ]
- Safety: number of adverse events, according to type and severity. [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]
|Study Start Date:||September 2004|
|Study Completion Date:||January 2007|
|Primary Completion Date:||January 2007 (Final data collection date for primary outcome measure)|
Even though the generated data on standard interferon for the treatment of chronic HBV-infection in HIV-coinfected patients appears not promising at the moment, it is however the only treatment with a curative intention. Trials with pegylated interferon in the treatment of chronic HBV-infection in monoinfected patients with pegylated interferons showed higher efficacy than standard of care and when compared to historic data higher efficacy compared to non-pegylated interferon. This suggests in parallel a higher efficacy in the treatment of chronic hepatitis B in HIV-coinfected as well. At the same time, analysis suggested a further benefit when pegylated interferon therapy was prolonged beyond 24 weeks to 48 weeks as the elimination of HBV-DNA from serum appeared to continue beyond 24 weeks. Looking again at data from chronic hepatitis C infection, it is well known that the elimination kinetics of HCV-RNA in HIV-coinfected patients is slower compared to HCV-monoinfected patients, clearly suggesting rationale to offer 48 weeks pegylated interferon for the treatment of chronic hepatitis B to HIV-coinfected patients as well.
Parallel to the above said there are several other factors suggesting a positive effect of a combination treatment with nucleoside / nucleotide analogues active against HBV and interferon. Therefore patients in need for antiretroviral therapy with CD4-cells above 200/µl will be randomized to either PegIFN as part of a combination treatment with FTC and TDF or to FTC / TDF combination therapy alone. Patients receiving HAART will also receive a third active antiretroviral HIV-drug, either a non-nucleoside analogue (NNRTI) or a protease inhibitor (PI), at the choice of the investigator. A non-divergent antiretroviral therapy solely based on nucleoside analogues will not be allowed in this trial.
The objective of this study is to assess the efficacy (HBV-DNA < 5x10³ copies/ml, loss of HBe-Ag, HBe-seroconversion) and safety (adverse events, serious adverse events) of PegIFN for 48 weeks, to that of PegIFN for 48 weeks plus TDF and FTC containing HAART, to that of TDF and FTC containing HAART for 72 weeks.
|Abteilung Klinische Immunologie Zentrum Innere Medizin der Medizinischen Hochschule Hannover|
|Hannover, Lower Saxony, Germany, 30625|
|Immunologische Ambulanz, Medizinische Klinik und Poliklinik I, Bonn University|
|Bonn, North-Rhine Westfalia, Germany, 53127|
|Berlin, Germany, 14057|
|ifi Institut für Interdisziplinäre Medizin|
|Hamburg, Germany, 20099|
|Praxis St. Georg|
|Hamburg, Germany, 20099|
|Study Director:||Jürgen K Rockstroh, MD, PhD||Bonn University, Germany|
|Principal Investigator:||Martin - Vogel, MD||Bonn University|