Live Zoster Vaccine in HIV-Infected Adults on Antiretroviral Therapy

Phase 2

Completed

Conditions: Herpes Zoster
HIV Infections

Interventions: Biological: ZOSTAVAX
Biological: Placebo

Registration Number: NCT00851786

Lead Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Brief Summary: Herpes zoster, or shingles, is the result of a viral infection that causes a painful skin rash, usually in older people or people with suppressed immune systems like those infected with HIV. The ZOSTAVAX vaccine has been shown to reduce the number of infections and symptoms of herpes zoster infection in people over the age of 60. The purpose of this study is to evaluate the safety, tolerability, and immunogenicity of two doses of ZOSTAVAX in HIV-1-infected adults with conserved immune function (Cd4+ T cell counts \>=200 cells/uL) virologically suppressed on potent combination antiretroviral therapy (ART).

Detailed Description: The varicella-zoster virus (VZV) which causes herpes zoster (HZ), or shingles, is associated with a painful skin rash and post-herpetic neuralgia (PHN). The incidence and severity of HZ and PHN increase as immune function decreases, as in elderly or HIV-infected people. The live VZV vaccine, ZOSTAVAX, has been shown to reduce the incidence and severity of HZ and PHN in people over the age of 60. The main purpose of this study is to determine whether a two-dose regimen of ZOSTAVAX is safe and well-tolerated in HIV-infected individuals with conserved immune function.

This study has two stages and two arms. It may last up to 24 weeks per subject. In Stage 1, 48 participants with CD4 cell counts of 200 or more cells/uL will be enrolled (24 participants with a CD4 count between 200 and 349 cells/uL and 24 participants with a CD4 count equaling 350 or more cells/uL). These participants will be randomized 3:1 to receive two doses of ZOSTAVAX or placebo at least six weeks apart. If certain safety criteria are met for Stage 1, enrollment will be opened to Stage 2. Stage 2 will enroll approximately 352 subjects with CD4+ T cell counts \>= 200 cells/uL. In Stage 2, participants will be stratified using the same parameters as Stage 1 and will then be randomized 3:1 to receive either two doses of vaccine or placebo according to the same schedule. Participants will be followed for at least 42 days after each vaccination. Temperatures will be collected daily for 42 days following each vaccination. Telephone contact will also be made 2 to 3 days after each vaccination and at 24 weeks following the initial vaccination to obtain information regarding vaccination-related symptoms.

All participants will have between 6 and 8 study visits. At the screening visit, documentation of HIV status is required, and blood and urine collection, a physical exam, medical history, and clinical assessment will occur. At each visit, a targeted physical exam will occur. At some visits, blood and urine collection, and a clinical assessment will occur. Antiretroviral medications are not provided by this study.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 395

Inclusion Criteria

HIV infected
Use of potent combination ART regimen within 90 days prior to entry and undetectable plasma HIV RNA level within 90-210 days prior to study entry
CD4 cell count of at least 200 cells/uL obtained within 30 days prior to study entry
Laboratory values obtained within 90 days prior to study entry
- Hemoglobin 7.0 g/dL or greater
- Platelet count 50,000/mm3 or greater
- Creatinine 3 x ULN or less
- AST (SGOT), ALT (SGPT), and alkaline phosphatase 5 x ULN or less
For females of reproductive potential, a negative serum or urine pregnancy test within 24 hours prior to study entry
Willing to use accepted forms of contraception for the duration of the study
History of varicella or herpes zoster more than 1 year prior to vaccination or VZV seropositivity at any time prior to entry
Men and women age >=18 years
Ability and willingness of subject or legal guardian/representative to provide informed consent

Exclusion Criteria

History of nadir CD4+ count <100 cells/uL
Known or suspected immune dysfunction caused by a medical condition or any cause other than HIV infection, such as congenital immunodeficiency, organ or bone marrow transplantation, leukemia, lymphoma, Hodgkin's disease, multiple myeloma, or generalized malignancy [NOTE: Subjects with prostate or breast cancer who are not on chemotherapeutic drugs (other than hormone blocking drugs), subjects with skin cancer or Kaposi's sarcoma limited to skin who are not receiving radiation therapy or chemotherapy, and subjects with a history of other malignancies who have been disease-free for at least 5 years will be eligible for enrollment.]
Receipt of any varicella or zoster vaccine prior to study entry
History of allergy/sensitivity, or hypersensitivity to any vaccine component, including gelatin or neomycin
Receipt of immunoglobulin or any blood products, other than autologous blood transfusion, given during the 5 months prior to study entry or expected during the 24-week study period
Receipt of any live virus vaccine within 28 days prior to study entry or during study period
Receipt of any inactivated vaccine within 7 days prior to study entry or during study period
Scheduled administration of any live virus vaccine or inactivated vaccine at or between study entry and the Week 12 visit
Participation in an investigational drug study within the last 30 days prior to study entry
Use of immunosuppressive therapy. More information can be found in the protocol.
Any chronic suppressive antiviral therapy with activity against herpes viruses, including but not limited to acyclovir, famciclovir, valacyclovir, ganciclovir, foscarnet, and cidofovir within 7 days prior to study entry or expected use through the 24-week study period except where necessary for acute treatment of intercurrent viral infection.
Any episode of VZV reactivation in the 12 months prior to study entry
Active drug or alcohol use, dependence, or any other reason that, in the opinion of the site investigator, would interfere with the study
Pregnancy (including subjects who are expecting to conceive within 3 months of the second vaccination) or breast feeding
Any acute intercurrent illness that might interfere with the interpretation of the study
Significant underlying illness preventing completion of the study

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
1	ZOSTAVAX	Participants with CD4 cell counts of 200 cells/uL or greater in Stages 1 and 2, stratified by CD4 cell counts (200-349 cells/uL vs. \>=350 cells/uL), will be given one dose of ZOSTAVAX (Zoster Vaccine Live) at Day 0 and Week 6 and will be followed for at least 42 days after each vaccination after which a safety assessment will be conducted.
2	Placebo	Participants with CD4 cell counts of 200 cells/uL or greater in Stages 1 and 2, stratified by CD4 cell counts (200-349 cells/uL vs. \>=350 cells/uL), will be given one dose of placebo at Day 0 and Week 6 and will be followed for at least 42 days after each vaccination after which a safety assessment will be conducted

Primary Outcome Measures

Name	Time	Method
Number of Participants With Composite Safety Endpoint of the Occurrence of Serious Adverse Events (SAEs) or Division of AIDS (DAIDS) Grade 3 and 4 Signs and Symptoms, Excluding SAEs Related to Trauma	During the 6 week study period after receipt of any dose of ZOSTAVAX	Although the study was designed as a randomized trial, it was not powered to detect safety related differences between treatment arms. The safety of ZOSTAVAX was determined by comparing the number of subjects from the active arm who experienced safety endpoint to the number from a pre-specified decision rule, which was calculated based on a similar population and calibrated using the number of safety endpoints observed from the placebo arm. The pre-specified decision rule is that ZOSTAVAX would be considered to have acceptable safety if no more than 18 subjects experience a study-defined composite safety endpoint.

Secondary Outcome Measures

Name	Time	Method
Geometric Mean Fold Rise (GMFR) in VZV ELISpot Responses	Entry, Week 6, Week 12	VZV-specific cellular immune responses in peripheral blood mononuclear cells (PBMC) were tested by ELISpot assay in a subset of participants pooled across CD4 strata. GMFR is the geometric mean of the ratios of Week 6 or Week 12 post-vaccination antibody to the pre-vaccination antibody.
VZV Antibodies as Measured by gpELISA	Within 6 weeks following one or two doses of ZOSTAVAX	VZV antibody titer measured by gpELISA after one or two doses of ZOSTAVAX/placebo

Trial Locations

Locations (43): The Ponce de Leon Center CRS
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Atlanta, Georgia, United States
The Ohio State University Medical Center
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Columbus, Ohio, United States
Thomas Jefferson Univ. Med. Ctr. CRS
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Philadelphia, Pennsylvania, United States
MetroHealth CRS
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Cleveland, Ohio, United States
Univ. of Cincinnati CRS
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Cincinnati, Ohio, United States
Univ. of Miami AIDS CRS
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Miami, Florida, United States
UCLA CARE Center CRS
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Los Angeles, California, United States
University of Southern California CRS
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Los Angeles, California, United States
Stanford CRS
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Palo Alto, California, United States
Ucsd, Avrc Crs
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San Diego, California, United States
Harbor-UCLA Med. Ctr. CRS
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Torrance, California, United States
University of Colorado Hospital CRS
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Aurora, Colorado, United States
Northwestern University CRS
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Chicago, Illinois, United States
Johns Hopkins Adult AIDS CRS
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Baltimore, Maryland, United States
Rush Univ. Med. Ctr. ACTG CRS
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Chicago, Illinois, United States
Brigham and Women's Hosp. ACTG CRS
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Boston, Massachusetts, United States
IHV Baltimore Treatment CRS
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Baltimore, Maryland, United States
Beth Israel Deaconess Med. Ctr., ACTG CRS
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Boston, Massachusetts, United States
Bmc Actg Crs
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Boston, Massachusetts, United States
Cooper Univ. Hosp. CRS
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Camden, New Jersey, United States
Washington U CRS
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Saint Louis, Missouri, United States
New Jersey Medical School- Adult Clinical Research Ctr. CRS
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Newark, New Jersey, United States
Bronx-Lebanon Hosp. Ctr. CRS
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Bronx, New York, United States
NY Univ. HIV/AIDS CRS
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New York, New York, United States
Cornell CRS
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New York, New York, United States
HIV Prevention & Treatment CRS
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New York, New York, United States
Univ. of Rochester ACTG CRS
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Rochester, New York, United States
Chapel Hill CRS
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Chapel Hill, North Carolina, United States
Greensboro CRS
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Greensboro, North Carolina, United States
Case CRS
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Cleveland, Ohio, United States
Hosp. of the Univ. of Pennsylvania CRS
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Philadelphia, Pennsylvania, United States
The Miriam Hosp. ACTG CRS
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Providence, Rhode Island, United States
University of Washington AIDS CRS
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Seattle, Washington, United States
Pitt CRS
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Pittsburgh, Pennsylvania, United States
Georgetown University CRS (GU CRS)
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Washington, District of Columbia, United States
Massachusetts General Hospital ACTG CRS
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Boston, Massachusetts, United States
Alabama Therapeutics CRS
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Birmingham, Alabama, United States
Ucsf Aids Crs
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San Francisco, California, United States
Denver Public Health CRS
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Denver, Colorado, United States
Henry Ford Hosp. CRS
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Detroit, Michigan, United States
Duke Univ. Med. Ctr. Adult CRS
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Durham, North Carolina, United States
The Research & Education Group-Portland CRS
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Portland, Oregon, United States
Vanderbilt Therapeutics CRS
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Nashville, Tennessee, United States