The Yellow Fever Vaccine Immunity in HIV Infected Patients : Development of New Assays for Virological and Immunological Monitoring in HIV Infected Patient. (EP46 NOVAA)

French National Agency for Research on AIDS and Viral Hepatitis

Status and phase: Completed; Phase 3

Conditions: Yellow Fever; HIV Infection

Treatments: Biological: Yellow fever vaccination (STAMARIL)

Study type: Interventional

Funder types: Other

Identifiers

NCT01426243

2009-014921-17

Details and patient eligibility

About

Main objective :

To develop the tools for evaluation of humoral and cell-mediated immunity after Yellow Fever Vaccine (YFV) and compare virological and immune responses in HIV-positive and HIV-negative individuals who had not been given YFV before.

Secondary objectives :

• To develop and assess ELISPOT technology for yellow fever and to measure the response within 7, 14, 28, 90 and 365 days of administration of YFV in 30 HIV negative subjects and 40 HIV positive subjects (CD4 > 350/mm3 under Highly Active Antiretroviral Therapy (HAART) for at least one year, with a viral load < 50 copies/mL since at least 6 months) in terms of : (1) seroconversion by fluorescence, (2) cytotoxic response in ELISPOT, (3) neutralizing antibody levels in Plaque reduction neutralization test (PRNT:reference method) and a new pseudotype based method, (4) post-vaccination viremia and (5) diversity of viral quasi-species.
• To assess the impact of YFV on the T-lymphocyte response against HIV by ELISPOT and viral load.

Full description

Method :

Clinical Trial Phase III, Multicentre protocol at Saint-Louis hospital, Bichat hospital and Cochin-Pasteur hospital, with CERVI, INSERM U 941 and SC10 collaboration.

Trial treatment : Yellow fever vaccination (STAMARIL)

Criterion :

Immuno-virologic: At J-7, J7, J28, M3 and M12 will be determined the levels of antibodies by fluorescence, at J0, J7, J28, M3 and M12 titles and neutralization with Prnt pseudotypes, the ELISPOT response anti-yellow fever, viremia with quantitative analysis and nucleotide sequences on phylogenetic strains of viremia. Titles and Amariles kinetics of viremia, neutralizing antibodies and ELISPOT will be considered as surrogate markers of response in terms of groups.

Clinical and biological tolerance: At all follows up will be measured the incidence of CDC classification events (for HIV+) and general and local reactions of degree ≥ 2 in the setting of the injection of STAMARIL®.

Schedule :

Date of first enrolment : third quarter 2011. Inclusion period : 18 months. For each subject, participation in this trial will be for 12 months.

Enrollment: 71 patients

Sex: All

Ages: 18 to 55 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion criteria

Group 1: Voluntary HIV positive subjects

Inclusion Criteria:

• Adults under HAART for at least one year (and stable on treatment for at least 3 months prior to enrolment)
• > 350 CD4/mm3 (with half of them a nadir < 200 CD4/mm3) and a viral load < 50 copies/mL for at least 6 months.
• Patients were HCV negative or non-replicative and treated for at least 2 years with normal ALT and negative HBs antigen.

Exclusion Criteria:

• Previous vaccination against yellow fever or yellow fever Fluorescence anti-IgG positive.
• Administration of immunoglobulins < 3 months or any vaccine <1 month.
• Pregnancy ongoing or planned during the study.
• Coinfection with HCV virus untreated.
• HBs Ag positive.
• Hypersensitivity reaction to eggs / chicken protein; hereditary fructose intolerance.
• Immunosuppression, whether congenital, idiopathic or as a result of corticosteroids systemically (at doses ≥ 20mg/d of prednisone), or due to radiation or antineoplastic older than 6 months.
• History of thymic dysfunction (including thymoma and thymectomy).
• For HIV + subjects: ART Celsentri or by other anti-CCR5.

Group 2: HIV negative subjects

Inclusion Criteria:

HIV and HCV negatives

Exclusion Criteria:

• Previous vaccination against yellow fever or yellow fever Fluorescence anti-IgG positive.
• Administration of immunoglobulins < 3 months or any vaccine <1 month.
• Other vaccinations should be deferred beyond M3.
• Pregnancy ongoing or planned during the study.
• Coinfection with HCV virus untreated.
• HBs Ag positive.
• Hypersensitivity reaction to eggs / chicken protein; hereditary fructose intolerance.
• Immunosuppression, whether congenital, idiopathic or as a result of corticosteroids systemically (at doses ≥ 20mg/d of prednisone), or due to radiation or antineoplastic older than 6 months.
• History of thymic dysfunction (including thymoma and thymectomy).
• For HIV + subjects: ART Celsentri or by other anti-CCR5, coinfection with HCV virus untreated

Trial design

Primary purpose: Prevention

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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71 participants in 2 patient groups

Voluntary HIV positive subjects

Active Comparator group

Description:

40 HIV positive adults under HAART for at least one year (and stable on treatment for at least 3 months prior to enrolment), \> 350 CD4/mm3 (with half of them a nadir \< 200 CD4/mm3) and a viral load \< 50 copies/mL for at least 6 months. Patients were HCV negative or non-replicative and treated for at least 2 years with normal ALT and negative HBs antigen.

Treatment:

Biological: Yellow fever vaccination (STAMARIL)

Biological: Yellow fever vaccination (STAMARIL)

HIV negative subjects

Other group

Description:

Voluntary HIV negative subjects matched according to age (18-40 years and 40-55 years) and with HIV positive subjects, vaccinated at J0 and followed over one year

Treatment:

Biological: Yellow fever vaccination (STAMARIL)

Biological: Yellow fever vaccination (STAMARIL)