Clinical trial NCT01426243: The Yellow Fever Vaccine Immunity in HIV Infected Patients : Development of New Assays for Virological and Immunological Monitoring in HIV Infected Patient.
Official title: The Yellow Fever Vaccine Immunity in HIV Infected Patients : Development of New Assays for Virological and Immunological Monitoring in HIV Infected Patient
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: HIV Infection
Yellow Fever
Lead sponsor: ANRS, Emerging Infectious Diseases
Sponsor class: OTHER_GOV
First posted: 2011-08-31
Enrollment: 71
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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 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.

Eligibility 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

Primary outcomes:
measure: Immuno-virologic criterion
timeFrame: DAY-7
measure: Immuno-virologic criterion
timeFrame: Day 0
measure: Immuno-virologic criterion
timeFrame: Day 28
measure: Immuno-virologic criterion
timeFrame: Month 3
measure: Immuno-virologic criterion
timeFrame: Month 12
measure: Immuno-virologic criterion
timeFrame: Day 7
Secondary outcomes:
measure: Clinical and biological tolerance
timeFrame: day -7
measure: clinical and biological tolerance
timeFrame: day 0
measure: clinical and biological tolerance
timeFrame: day 7
measure: clinical and biological tolerance
timeFrame: day 14
measure: clinical and biological tolerance
timeFrame: day 28
measure: clinical and biological tolerance
timeFrame: month 3
measure: clinical and biological tolerance
timeFrame: month 12
Other outcomes:
Locations:
city: Paris
country: France
facility: Voir Liste Des Centres
Study officials:
affiliation: Maladies Infectieuses St Louis Paris
name: Nathalie COLIN de VERDIERE
role: PRINCIPAL_INVESTIGATOR
affiliation: Maladies Infectieuses et Tropicales Bichat Paris
name: Sophie MATHERON
role: PRINCIPAL_INVESTIGATOR
affiliation: CIC Cochin Paris
name: Odile LAUNAY
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.