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

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

Study Overview

• Status: Withdrawn
• Conditions: Herpes Zoster
• Intervention / Treatment: Biological: Zostavax

• Study Type: Interventional
• Phase: Phase 2; Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

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

Collaborators and Investigators

• Sponsor: University of Zurich
• Investigators: Principal Investigator: Barbara Hasse, MD, University Hospital Zurich, Div of Infectious Diseases and Hospital Epidemiology

Study record dates

Study Major Dates

• Study Start: December 1, 2010
• Primary Completion (Anticipated): December 1, 2011
• Study Completion (Anticipated): June 1, 2012

Study Registration Dates

• First Submitted: August 13, 2010
• First Submitted That Met QC Criteria: October 1, 2010
• First Posted (Estimate): October 4, 2010

Study Record Updates

• Last Update Posted (Estimate): March 1, 2013
• Last Update Submitted That Met QC Criteria: February 28, 2013
• Last Verified: February 1, 2013

More Information

Terms related to this study

• Keywords: safety; HIV; vaccine; immunogenicity; T cell; VZV (Varicella zoster Virus)
• Additional Relevant MeSH Terms: Virus Diseases; Infections; DNA Virus Infections; Herpesviridae Infections; Varicella Zoster Virus Infection; Herpes Zoster
• Other Study ID Numbers: SHCS 610