Efficacy and Tolerance of Peg-interferon Alpha 2a Added to Tenofovir and Emtricitabine in AgHBe Positive HBV-HIV Co-infected Patients - Full Text View

Purpose

HBe seroconversion is an important goal for anti-HBV treatment, since it is associated with a non progressive liver infection and a better clinical outcome. However, the rate of HBe seroconversion is low in HIV-HBV co-infected patients, mostly treated by tenofovir and emtricitabine. This study will evaluate the efficacy and the safety of a one-year Peg-interferon alpha 2a additional treatment in patients already treated by tenofovir and emtricitabine without reaching HBe seroconversion.

Condition	Intervention	Phase
Hepatitis B HIV Infections	Drug: TRUVADA (EMTRICITABINE + TENOFOVIR DF) Biological: PEGASYS 180μg (Interféron pégylé alpha -2a)	Phase 2 Phase 3

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Pilot Study on Efficacy and Tolerance of Peg-interferon Alpha-2a (Pegasys) Added to Tenofovir DF and Emtricitabine (Truvada) in AGHBe Positive HBV-HIV Co-infected Patients. ANRS HB 01 EMVIPEG.

Resource links provided by NLM:

Genetics Home Reference related topics: complement factor I deficiency

MedlinePlus related topics: HIV/AIDS Hepatitis Hepatitis A Hepatitis B

Drug Information available for: Interferon Interferon Alfa-2a Emtricitabine Tenofovir Peginterferon Alfa-2a Tenofovir Disoproxil Fumarate Truvada

U.S. FDA Resources

Further study details as provided by French National Agency for Research on AIDS and Viral Hepatitis:

Primary Outcome Measures:

proportion of patients with seroconversion HBe (loose of HBe antigen and acquisition of HBe antibody) and HBV DNA below 2.3 log10 copies per ml [ Time Frame: at W 72 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

proportion of patients with negative HBe antigen. [ Time Frame: at W 72 ] [ Designated as safety issue: No ]
proportion of patients with HBV DNA under 2.3 log 10 copies per ml. [ Time Frame: at W72 ] [ Designated as safety issue: No ]
proportion of seroconversion HBs. [ Time Frame: at W72 ] [ Designated as safety issue: No ]
proportion of patients with no more HBs antigen. [ Time Frame: at W72 ] [ Designated as safety issue: No ]
proportion of patients with HBV DNA below 2.3 log 10 copies per ml in relation with 3TC resistance or not before tenofovir treatment; increased of ALT before tenofovir treatment;duration of tenofovir treatment before study. [ Time Frame: before tenofovir treatment, duration of tenofovir treatment before study ] [ Designated as safety issue: No ]
Biological evolution and histological of hepatic activity and fibrosis. [ Time Frame: at W 0 and W 72 ] [ Designated as safety issue: No ]
Biochemical response (ALT at normal value). [ Time Frame: at W 72 ] [ Designated as safety issue: No ]
proportion of patients with :seroconversion HBe and HBV DNA below 2.3 log 10 copies per ml [ Time Frame: at W 48 ] [ Designated as safety issue: No ]
HBV and HIV resistance mutations to tenofovir DF and Emtricitabine. [ Time Frame: at W 72 ] [ Designated as safety issue: No ]
Immunological and virological evolution of HIV infection. [ Time Frame: between W 0 and W 144 ] [ Designated as safety issue: No ]
Safety [ Time Frame: between W 0 and W 144 ] [ Designated as safety issue: Yes ]
Quality of life [ Time Frame: W 0, W12, W24, W48, W72 ] [ Designated as safety issue: No ]

Enrollment:	56
Study Start Date:	January 2007
Estimated Study Completion Date:	October 2012
Primary Completion Date:	May 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: HIV antiretroviral therapy, TRUVADA , PEGASYS 180μg Week-8 up Week0: HIV antiretroviral therapy Week 0 up Week 48: HIV antiretroviral therapy + TRUVADA + PEGASYS 180μg Week 48 up Week 72: HIV antiretroviral therapy + TRUVADA Week 72 up Week 144: HIV antiretroviral therapy	Drug: TRUVADA (EMTRICITABINE + TENOFOVIR DF) Truvada ® (200 mg tablet of 300 mg of emtricitabine + tenofovir DF) Dosage 1 tablet taken orally once a day Biological: PEGASYS 180μg (Interféron pégylé alpha -2a) Pegasys ® injection 180μg Dosage: A subcutaneous injection per week

Detailed Description:

Many HBV-HIV co-infected patients are currently treated with dual activity drugs such as tenofovir and emtricitabine, often in combination. However, despite the potent antiviral activity of these drugs, the rate of HBe seroconversion is quite low, and not always sustained over time. HBe seroconversion is an important goal for anti-HBV treatment, since it is associated with a non progressive liver infection and a better clinical outcome. On the other hand, treatments with antiviral and immuno-modulator activity such as Peg-interferon, are infrequently used in co-infected patients, despite promising data in the field of HBV mono-infection with increased rates and sustained HBe seroconversions. This pilot study will evaluate the efficacy and the safety of a one-year Peg-interferon alpha 2a additional treatment (180 micro-g once a week, by injection), in 55 patients already treated by tenofovir and emtricitabine for at least 6 months, and who did not reached HBe seroconversion

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

HIV infection
Karnofsky above 80 per cent
Stable ARV since 4 months
CD4 above 200 per mm3
ARN VIH below 10000 copies per ml
hepatitis B chronic with : positive antigenaemia HBe and negative antiHBe, positive DNA HBV before or under tenofovir treatment, DNA HBV negative or below 10000 copies per ml at W-8.
Previous treatment by tenofovir and lamivudine or emtricitabine more than 6 months

Exclusion Criteria:

HIV 2 infection
Hepatitis C or D
Opportunistic infection
Alcool consummation more than 50g/d
Cirrhosis
Pregnancy or plan of pregnancy
Breastfeeding
Immunosuppressive or modulating of the immune response treatment
Other Hepatitis B treatments than tenofovir, lamivudine or emtricitabine since 6 months
Malabsorption
Exclusive HIV therapy with Truvada
Evolutive cancer under chemotherapy

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00391638

Locations

France
Service des Maladies Infectieuses CHU
Dijon cedex, France, 21079
Service d'Hépato-Gastroentérologie Hopital Hôtel-Dieu
Lyon Cedex 02, France, 69288

Sponsors and Collaborators

French National Agency for Research on AIDS and Viral Hepatitis

Gilead Sciences

Roche Pharma AG

Investigators

Principal Investigator:	Lionel Piroth, MD	CHU Dijon France
Study Chair:	Fabrice Carrat, MD	Inserm U 707 Paris France

More Information

No publications provided

Responsible Party:	French National Agency for Research on AIDS and Viral Hepatitis
ClinicalTrials.gov Identifier:	NCT00391638 History of Changes
Other Study ID Numbers:	2006-004137-15, ANRS HB 01 EMVIPEG
Study First Received:	October 23, 2006
Last Updated:	February 21, 2012
Health Authority:	France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by French National Agency for Research on AIDS and Viral Hepatitis:

HIV and Hepatitis B coinfection
Peg interferon
tenofovir

emtricitabine
Hepatitis B e Antigens
Treatment Experienced

Additional relevant MeSH terms:

HIV Infections
Acquired Immunodeficiency Syndrome
Hepatitis
Hepatitis A
Hepatitis B
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Liver Diseases

Digestive System Diseases
Hepatitis, Viral, Human
Enterovirus Infections
Picornaviridae Infections
Hepadnaviridae Infections
DNA Virus Infections
Interferon-alpha
Interferon Alfa-2a
Interferons
Tenofovir
Tenofovir disoproxil
Peginterferon alfa-2a
Emtricitabine
Antiviral Agents
Anti-Infective Agents

ClinicalTrials.gov processed this record on May 22, 2013