Clinical trial NCT00391638: Efficacy and Tolerance of Peg-interferon Alpha 2a Added to Tenofovir and Emtricitabine in AgHBe Positive HBV-HIV Co-infected Patients
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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Hepatitis B
HIV Infections
Keywords: HIV and Hepatitis B coinfection
Peg interferon
tenofovir
emtricitabine
Hepatitis B e Antigens
Treatment Experienced
Lead sponsor: ANRS, Emerging Infectious Diseases
Sponsor class: OTHER_GOV
Collaborators: name: Gilead Sciences
name: Roche Pharma AG
First posted: 2006-10-24
Enrollment: 56
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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 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

Primary outcomes:
measure: 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
timeFrame: at Week 72
Secondary outcomes:
measure: proportion of patients with negative HBe antigen.
timeFrame: at Week 72 and Week 144
measure: proportion of patients with HBV DNA under 2.3 log 10 copies per ml.
timeFrame: at Week 72 and Week 144
measure: proportion of seroconversion HBs.
timeFrame: at Week 72 and Week 144
measure: proportion of patients with no more HBs antigen.
timeFrame: at Week 72 and Week 144
measure: 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.
timeFrame: before tenofovir treatment, duration of tenofovir treatment before study
measure: Biological evolution and histological of hepatic activity and fibrosis.
timeFrame: at day 0 and Week 72
measure: Biochemical response (ALT at normal value).
timeFrame: at Week 72 and Week 144
measure: proportion of patients with :seroconversion HBe and HBV DNA below 2.3 log 10 copies per ml
timeFrame: at Week 48
measure: HBV and HIV resistance mutations to tenofovir DF and Emtricitabine.
timeFrame: at Week 72
measure: Immunological and virological evolution of HIV infection.
timeFrame: between Day 0 and Week 144
measure: Safety
timeFrame: between Day 0 and Week 144
measure: Quality of life
timeFrame: Day 0, Week 12, Week 24, Week 48, Week 72
measure: Treatment adherence
timeFrame: Day 0 to Week 144
Other outcomes:
Locations:
city: Dijon cedex
country: France
facility: Service des Maladies Infectieuses CHU
city: Lyon Cedex 02
country: France
facility: Service d'Hépato-Gastroentérologie Hopital Hôtel-Dieu
Study officials:
affiliation: Centre Hospitalier Universitaire Dijon
name: Lionel Piroth, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Inserm U 707 Paris France
name: Fabrice Carrat, MD
role: STUDY_CHAIR
References: