Prevention of Varicella Zoster Virus (VZV)-Reactivation in HIV-positive Individuals Enrolled in a Prospective Immunogenicity and Safety Trial of VZV Vaccine: PROVE-IT-Study

Study Overview
=================
Brief Summary
-----------------
The goal is to demonstrate the immunogenicity and safety of Zostavax® in HIV positive individuals. Study participants are stratified into different patient groups according to their CD4 cell count, viral load and HIV Status. Trial with medicinal product Trial with immunomodulatory product / biological

Conditions
-----------------
Herpes Zoster

Intervention / Treatment
-----------------
* Biological: Zostavax


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion criteria: All individuals Age >18 years Male, or female with negative urine pregnancy test VZV-seropositive (serologically documented) Agree to use a barrier method of birth control (such as a condom) Written informed consent HIV positive individuals on ART (group A1-A3) Continuous ART for >3 months before baseline No change of ART regimen within 1 month before baseline HIV-RNA (value must be <3 months old )<50 copies/ml at last visit CD4-count (value must be <3 months old) > 500 cells/µl for group A1, 350-500 cells/µl for group A2 and 250 -349 cells/µl for group A3 Participation in the SHCS HIV-positive individuals without ART (group B) HIV-1 RNA >1000 copies/ml (<3 months before baseline) CD4-cell count >500 cells/µl (<3 months before baseline) Participation in the SHCS Healthy HIV-negative volunteers (group C) Negative HIV-screening test (<3 months before baseline) CD4 cell count >500 cells/µl Exclusion criteria: Common exclusion criteria Contraindications on ethical grounds Involvement in a conflicting (vaccine or investigational drug) clinical trial (except from the participation in the Swiss HIV Cohort Study). Inability to follow the procedures of the study, e.g. due to language problems, psychological disorders or dementia of the subject. Pregnancy or breast feeding. Other clinically relevant concomitant disease states (e.g., renal failure, hepatic dysfunction, cardiovascular disease, etc), Known or suspected non-compliance, drug- or alcohol abuse. Specific exclusion criteria Fever > 38.3 °C or acute illness during the last 4 weeks Exposure to chickenpox or shingles within four weeks prior to study entry History of shingles Immunosuppression due to disease (other than HIV) or due to medication within 30 days of study entry (eg corticosteroids) Household contact with known immunodeficiency (e.g. HIV-positive with CD4 <250 cells/µl) Immunoglobulin or blood product treatment within 1 year prior or 2 month after study vaccination Previous allergic reaction to vaccine components (i.e. neomycin or gelatin) Vaccination with a life attenuated vaccine one month prior to study entry History of chickenpox vaccination Treatment with anti-herpes drugs 4 weeks before baseline Severe coagulation disorder or oral anticoagulant treatment Laboratory exclusion criteria. Thrombocytopenia < 50x 103/?l Haemoglobin <12 g/dl More than threefold elevation of ALT Creatinine of more than150 µmol/l Glucose >10 mmol/l

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Single


Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: Zostavax|Biological/Vaccine|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Immunogenicity | Geometric mean titer of Varicella zoster virus-specific IgG, VZV-specific T- cells per 106 peripheral mononuclear cells, Frequency of VZV-specific T- cells of total T-cells, CD4+ T-cells in different HIV-positive persons. | half a year | 
| Safety | Number of Participants with Adverse Events as a Measure of Safety and Tolerability | half a year | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
HIV, VZV (Varicella zoster Virus), vaccine, T cell, immunogenicity, safety