Immune Response of Shingrix Vaccine in People Living With HIV (> 50 y.o.) Compared to Age-matched Controls

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficacy and safety of the adjuvanted recombinant Zoster vaccine (RZV, or Shingrix®) in older people (> 50 years) living with HIV (PLWH) compared to age-matched healthy adults over a 1-year period.

Detailed Description
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This is a prospective multicentric phase IV study, aiming at evaluating the immunogenicity and safety profile of RZV in PLWH over 50 years of age (YOA) on long term antiretroviral therapy (ART) (>10 years) compared to non-HIV age-matched adult controls to address the combined effect of aging and immunosuppression from HIV disease. Inclusion will be stratified as follow: HIV+ groups: Group 1: PLWH registered in the SHCS or ANRS CO3, >75 YOA and under cART for more than 10 years - N=50 Group 2: PLWH patients registered in the SHCS, aged between 60 and 75 and under cART for more than 10 years - N=50 Group 3: PLWH patients registered in the SHCS, aged between 50 and 59 and under cART for more than 10 years - N=50 Control groups: Group 4: Healthy adults aged >75 YOA- N=25 Group 5: Healthy adults aged between 60 and 75 - N=25 Group 6: Healthy adults aged between 50 and 59 - N=25 In addition, participants of all groups will be proposed to be included in the Innate substudy (target of 15 participants/group) and have two additional blood drawings 1 day after each vaccine dose to measure innate response triggered by RZV. Participants will receive Shingrix® on Day0 and Day60; immunological response will be assessed on Day 1, Day61, Day90, Day360. Unsolicited Adverse events of special intesrest (AESI) will be collected on Day 28, Day 60, Day90, Day360; patients reported outcomes (PROs) will be declared for one week after each vaccination.

Official Title
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Immune Response to the Recombinant Zoster Vaccine in People Living With HIV Over 50 Years of Age Compared to Non-HIV Age- and Gender-matched Controls - The Shingr'HIV Phase IV Multicenter Study

Conditions
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RZV Vaccine (Shingrix ®)

Intervention / Treatment
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* Biological: Recombinant Zoster Vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: For PLWH: Be registered in the SHCS or in the ANRS CO3 Aquitaine Cohort Age >50 YOA Time since cART initiation > 10 years Not already vaccinated with RZV HIV viral load <50 copies/ml (within 6 months from the last blood sampling) Informed consent as documented by signature (France) : Person affiliated with or beneficiary of the French social security scheme For aged/gender-matched controls Age >50 YOA Not already vaccinated with RZV Informed consent as documented by signature (France) Not HIV infected (France) Person affiliated with or beneficiary of the French social security scheme Exclusion Criteria: Ongoing signs of febrile or non-febrile infection at the time of the first vaccination Immunosuppression from the following: Current malignant neoplasm; primary immunodeficiency; recent (<2 years) solid or bone-marrow transplant or any transplant still requiring immunosuppressive therapy Intake of drugs which suppress the immune system (e.g. glucocorticoids for a long time [an equivalent dose of prednisolone >20 mg/day > 3 months], monoclonal antibodies, cytostatics, biological products, etc.) within 6 months before screening. Administration of immunoglobulins or any blood products within 3 months preceding the first dose of vaccine or planned administration during the study period Having received a vaccine in the last month or is expected to receive a vaccine in the next month Having received a shingles vaccine within one year Presented with herpes zoster in the previous year Contra-indication to RZV Hospitalized patients Unable to provide informed consent or inability to follow the procedures of the study, e.g. due to language problems, psychological disorders, dementia, etc. of the participant Participation in another study with investigational drug within the 30 days preceding and during the present study. (France) Pregnant or breastfeeding woman (France) Patient governed by articles L 1121-5 to L 1121-8 (persons deprived of their liberty by a judicial or administrative decision, minors, persons of legal age who are the object of a legal protection measure or unable to express their consent)

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 95 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: RZV or Shingrix®)<br>Recombinant Zoster Vaccine | Biological: Recombinant Zoster Vaccine<br>* Shingrix® vaccine will be administered in two vaccinations on Day0 and Day60<br>* Other names: (Shingrix® );|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Geometric mean titer (GMT) of gE-specific total IgG | gE-specific total IgG titers is determined by gE-specific ELISA from sera samples | Day 90 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Vaccine safety - AESI 7 days | Incidence adverse events of special interest (AESI) in the 7 days following each vaccination (reactogenicity) collected in a diary card | 7 days | 
| Vaccine safety - SAE 360 days | Incidence of SAE throughout the study period | 360 days | 
| Vaccine safety -pIMDs | Incidence of potential immune mediated disorders (pIMDs) throughout the study period | 360 days | 
| Vaccine safety - PLWH | In PLWH: Percentage of PLWH with viral load >50 copies/ml one month after the second RZV vaccination (D90) | Day 90 | 
| Vaccine immunogenicity - CD4+ T cells | Mean of gE-specific CD4+ T cells expressing at least 2 activation markers (i.e. CD40L, IFN-gamma, IL-2 or TNF-alpha) per million of T cells, measured at D90 | Day 90 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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RZV vaccine, PLWH, Immune response, Safety