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

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

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

Brief Summary:

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.

Detailed Summary:

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.

Sponsor: French National Agency for Research on AIDS and Viral Hepatitis

Current Primary Outcome:

• Immuno-virologic criterion [ Time Frame: DAY-7 ]
  - At Day-7 will be determined the levels of antibodies by fluorescence.
• Immuno-virologic criterion [ Time Frame: Day 0 ]
  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
• Immuno-virologic criterion [ Time Frame: Day 28 ]
  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
• Immuno-virologic criterion [ Time Frame: Month 3 ]
  At Month 3 will be determined fluorescence, PRNT and ELISPOT.
• Immuno-virologic criterion [ Time Frame: Month 12 ]
  At Month 12 will be determined fluorescence, PRNT and ELISPOT.
• Immuno-virologic criterion [ Time Frame: Day 7 ]
  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

Original Primary Outcome:

• Immuno-virologic criterion [ Time Frame: D-7 ]
  - At D-7 will be determined the levels of antibodies by fluorescence.
• Immuno-virologic criterion [ Time Frame: D7 ]
  At D-7 will be determined the levels of antibodies by fluorescence.
• Immuno-virologic criterion [ Time Frame: D 0 ]
  At D0 will be determined titles and neutralization with PRNT-Pseudotypes, ELISPOT response anti-yellow fever.
• Immuno-virologic criterion [ Time Frame: D28 ]
  - At D28 will be determined fluorescence, PRNT, ELISPOT , quantitative viremia and phylogenetic analysis.
• Immuno-virologic criterion [ Time Frame: M3 ]
  At M3 will be determined fluorescence, PRNT and ELISPOT.
• Immuno-virologic criterion [ Time Frame: M12 ]
  - At M12 will be determined fluorescence, PRNT and ELISPOT.

Current Secondary Outcome:

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

Original Secondary Outcome: clinical and biological tolerance [ Time Frame: D-7,D0, D7, D14, D28, M3 and M12 ]

Information By: French National Institute for Health and Medical Research-French National Agency for Research on AID

Dates:
Date Received: February 10, 2011
Date Started: July 2011
Date Completion: July 2017
Last Updated: July 21, 2016
Last Verified: July 2016