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

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

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.

Study Overview

• Status: Completed
• Conditions: HIV Infection; Yellow Fever
• Intervention / Treatment: Biological: Yellow fever vaccination (STAMARIL)

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 71
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Paris, France
    • Voir Liste Des Centres

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Voluntary HIV positive subjects; 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.	Biological: Yellow fever vaccination (STAMARIL); Yellow fever vaccination (STAMARIL)
Other: HIV negative subjects; 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	Biological: Yellow fever vaccination (STAMARIL); Yellow fever vaccination (STAMARIL)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Immuno-virologic criterion	- At Day-7 will be determined the levels of antibodies by fluorescence.	DAY-7
Immuno-virologic criterion	At Day 0 will be determined titles and neutralization with Prnt pseudotypes, the ELISPOT response anti-yellow fever, viremia with quantitative analysis and nucleotide sequences on phylogenetic strains of viremia	Day 0
Immuno-virologic criterion	At Day 28 will be determined titles and neutralization with Prnt pseudotypes, the ELISPOT response anti-yellow fever, viremia with quantitative analysis (if it's positive at day7) and nucleotide sequences on phylogenetic strains of viremia	Day 28
Immuno-virologic criterion	At Month 3 will be determined fluorescence, PRNT and ELISPOT.	Month 3
Immuno-virologic criterion	At Month 12 will be determined fluorescence, PRNT and ELISPOT.	Month 12
Immuno-virologic criterion	At Day 7 will be determined titles and neutralization with Prnt pseudotypes, the ELISPOT response anti-yellow fever, viremia with quantitative analysis and nucleotide sequences on phylogenetic strains of viremia	Day 7

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical and biological tolerance	At Day -7 will be determined the levels of antibodies by fluorescence	day -7
clinical and biological tolerance	At Day 0: incidence of HIV+ event and general+local reactions of d°>2 after vaccination	day 0
clinical and biological tolerance	At Day7: incidence of HIV+ event and general+local reactions of d°>2 after vaccination	day 7
clinical and biological tolerance	At Day14:incidence of HIV+ event and general+local reactions of d°>2 after vaccination	day 14
clinical and biological tolerance	At Day 28:incidence of HIV+ event and general+local reactions of d°>2 after vaccination	day 28
clinical and biological tolerance	At Month3:incidence of HIV+ event and general+local reactions of d°>2 after vaccination	month 3
clinical and biological tolerance	At Month 12:incidence of HIV+ event and general+local reactions of d°>2 after vaccination	month 12

Collaborators and Investigators

• Sponsor: French National Agency for Research on AIDS and Viral Hepatitis
• Investigators: Principal Investigator: Nathalie COLIN de VERDIERE, Maladies Infectieuses St Louis Paris; Principal Investigator: Sophie MATHERON, Maladies Infectieuses et Tropicales Bichat Paris; Principal Investigator: Odile LAUNAY, CIC Cochin Paris

Publications and helpful links

General Publications

• Colin de Verdiere N, Durier C, Samri A, Meiffredy V, Launay O, Matheron S, Mercier-Delarue S, Even S, Aboulker JP, Molina JM, Autran B, Simon F; ANRS EP46 NOVAA Group. Immunogenicity and safety of yellow fever vaccine in HIV-1-infected patients. AIDS. 2018 Oct 23;32(16):2291-2299. doi: 10.1097/QAD.0000000000001963.

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: July 1, 2011
• Primary Completion (Actual): February 1, 2017
• Study Completion (Actual): December 1, 2017

Study Registration Dates

• First Submitted: February 10, 2011
• First Submitted That Met QC Criteria: August 30, 2011
• First Posted (Estimate): August 31, 2011

Study Record Updates

• Last Update Posted (Actual): January 18, 2019
• Last Update Submitted That Met QC Criteria: January 17, 2019
• Last Verified: February 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Arbovirus Infections; Vector Borne Diseases; Flavivirus Infections; Flaviviridae Infections; Body Temperature Changes; Hemorrhagic Fevers, Viral; Fever; Yellow Fever
• Other Study ID Numbers: 2009-014921-17