Immunogenicity and Safety of Recombinant Zoster Vaccine in People Living With HIV

Study Overview
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Brief Summary
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The purpose of this study is to compare the immunogenicity and safety of recombinant zoster vaccine according to CD4+ T-cell count and age in people living with HIV, and to provide evidence to guide immunization of people living with HIV.

Detailed Description
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HIV-infected individuals willing to receive recombinant zoster vaccine will be recruited at three study hospitals. Participants are divided into two groups based on CD4+ T cell count (HIV #1: CD4+ T cell count <300 cells/µL, HIV #2: CD4+ T cell count≥300 cells/µL). Target numbers are 50 and 50, respectively. Give 2 intramuscular doses of recombinant zoster vaccine 2 months apart. Contact by phone on days 3 and 7 after each dose to assess for adverse events. Evaluate immunogenicity at 1 month and 13 months after the second dose and safety. An interim analysis is planned after the first approximately 30 participants of each group complete a visit 13 months after 2nd dose. Evaluation for the safety is planned after the first approximately 10 participants of the HIV #2 arm complete a visit 13 months after 2nd dose.

Official Title
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Immunogenicity and Safety of Recombinant Zoster Vaccine in People Living With HIV

Conditions
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Vaccination; Infection, Vaccine Adverse Reaction

Intervention / Treatment
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* Biological: Recombinant zoster vaccination


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 19 years old or older, HIV-1 infected person who have voluntarily agreed to participate in the study. Have been taking antiviral medications stably for at least one month at the time of screening. Have a CD4+ T-cell count measured within one month of screening. Do not have AIDS-defining diseases (excluding oral thrush) or acute/uncontrolled opportunistic infection at the time of enrollment. Do not have uncontrolled chronic medical conditions other than HIV infection. Exclusion Criteria: Have received any type of zoster vaccine within 1 year. Have been diagnosed with chickenpox or shingles within 12 months. Have a history of severe allergy to any of the components of Shingrix vaccine. Have a acute medical condition at the time of screening. Unable to be evaluated for adverse events via telephone contact after vaccination. Pregnant (including those planning to become pregnant) or lactating women. Those who have received chemotherapy or radiotherapy within 6 months prior to the first vaccine dose. Chronic administration of immunosuppressive or other immune-modifying drugs within 6 months prior to ther first vaccine dose. Administration of immunoglobulins, and/or any blood products within 3 months preceding the first dose of study vaccine Have a medical condition that makes receiving an intramuscular injection medically contraindicated. Have a disease or condition that may affect the immunogenicity or safety of the vaccine. Receiving any other vaccine within 14 days prior to and 14 days after receiving the study vaccine. Participate in a clinical trial that involves other investigational product or device during the course of the study. Any other person who, in the opinion of the investigator, is unsuitable for immune response assessment.

Ages Eligible for Study
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Minimum Age: 19 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HIV #1<br>CD4+ T cell count <300 cells/µL | Biological: Recombinant zoster vaccination<br>* Two doses of recombinant zoster vaccine(Shingrix®), 2 months apart<br>|
| Active Comparator: HIV #2<br>CD4+ T cell count≥300 cells/µL | Biological: Recombinant zoster vaccination<br>* Two doses of recombinant zoster vaccine(Shingrix®), 2 months apart<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Humoral immune response | Defined as a 4-fold or greater increase in anti-VZV antibody concentration from pre-vaccination testing in seropositive subjects and a 4-fold or greater increase in anti-gE antibody concentration from the cutoff in seronegative subjects prior to vaccination. | 1 month, 13 months after 2nd dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cell-mediated immunogenicity | Defined as a 2-fold or greater increase in CD4+ T cells expressing at least two activation markers (i.e. CD40L, IFN-gamma, IL-2 or TNF-alpha) post-vaccination compared to pre-vaccination baseline. | 1 month, 13 months after 2nd dose | 
| Differences in humoral immune response and cell mediated immunogenecity | Comparison of geometric mean of anti VZV IgG titer and proportions of VZV-specific CD4+ and CD8+ T-cells between HIV#1 and HIV#2 | 1 month, 13 months after 2nd dose | 
| Grade 3/4 adverse events (AE) | Solicited and unsolicited local and systemic adverse events occurring within 7 days after the first and second dose | Within 7 days (Day 0-6) after the first and second dose. | 
| Any serious adverse events (SAEs) | Any serious adverse events occurring throughout the study period | Throughout the study period: Day 0 450 or termination, whichever came first | 
| Increase in HIV Viral Load or decrease in CD4+ T-cell Count | Increase in HIV Viral Load by 0.5 log or more or decrease in CD4+ T-cell Count by 30% or more | 1 month after 2nd dose | 
| Any AIDS-defining disease | Occurrence of any AIDS defining condition according to the appendix of the Revised surveillance case definition for HIV infection--United States, 2014 (Centers for Disease Controls and Prevention); | Within 3 months after 2nd dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Recombinant zoster vaccine, Vaccination of people living with HIV