Live Zoster Vaccine in HIV-Infected Adults on Antiretroviral Therapy

A Phase II, Randomized, Double-Blind, Placebo-Controlled Clinical Trial to Evaluate the Safety, Tolerability, and Immunogenicity of ZOSTAVAX® (Zoster Vaccine Live) in Human Immunodeficiency Virus (HIV)-1-Infected Adults on Potent Combination ART With Conserved Immune Function

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).

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.

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