Safety of and Immune Response to a Meningitis Vaccine in HIV-Infected Children and Youth
Condition: HIV Infections; Meningitis
MeSH terms: Meningitis
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      Bacterial meningitis infection is common in youth 2 to 24 years of age in the United States.
      This disease can be treated by antibiotics, but mortality rates associated with meningitis of
      up to 53% have been estimated. Vaccination against meningitis may be effective in preventing
      this disease, especially for HIV-infected youth who have weakened immune systems. The purpose
      of this study was to determine the safety of and immune response to a preventive meningitis
      vaccine in HIV-infected youth.
    

Detailed description: 
      In the United States, youth 2 to 24 years of age are at high risk for bacterial meningitis
      infection. Despite antibiotic treatment, the mortality rate for meningitis and sepsis can
      reach as high as 53% caused by Neisseria meningitidis. This rate could be higher in
      immunocompromised individuals, such as those infected with HIV. To prevent infection,
      vaccination against meningitis is recommended by the CDC at ages 11, 15, and 18. The
      quadrivalent meningococcal conjugate vaccine (MCV4) is a vaccine that has been observed to
      elicit an appropriate immune response to N. meningitidis and was approved by the FDA in
      January 2005. However, to date, no studies have been done to determine the safety and
      immunogenicity of this vaccine in HIV-infected individuals. The purpose of this study was to
      determine the safety and immunogenicity of MCV4 in HIV-infected youth 2 to 24 years of age.

      The study was originally designed for participants to be followed for 72 weeks. Participants
      were enrolled in three groups by age and CD4% as follows:

      Group 1: Age 11 to 24 years, CD4% of 15% or higher. Enrollment was further stratified by
      CD4%: 15% to <25%, and >= 25%.

      Group 2: Age 11 to 24 years, CD4% < 15%.

      Group 3: Age 2 to 10 years, CD4% of 25% or higher.

      At study entry, all study participants received one injection of MCV4 (Step 1). Participants
      were observed for 30 minutes post-injection to monitor for adverse events. A clinic visit was
      required 24 hours post-injection if the participant reported adverse events. At Week 24,
      participants in Group 1 who did not experience any disqualifying adverse events after the
      first injection were randomly assigned to receive a second injection of MCV4 or no further
      injections. Group 2, and Group 3 participants who had no disqualifying adverse events after
      the first injection received a second injection of MCV4 at Week 24 (Step 2).

      There were five study visits in Steps 1 and 2; they occurred at study entry and at Weeks 4,
      24, 28, and 72. At these visits, a physical exam, assessment of HIV-related symptoms, and
      blood collection occurred. In addition, study participants were contacted by telephone at
      Days 3 and 7 and Weeks 1, 6, and 25 after the first vaccination. Participants in Groups 1B
      and 2 who received a second injection were contacted by telephone at Weeks 30 and 48.

      As of November 2010, due to data from this study (P1065) and recommendations from the
      Advisory Committee for Immunization Practices (ACIP) of the Center for Disease Control (CDC),
      eligible participants in Groups 1 (1A and 1B) and 3 of P1065 received a booster dose of MCV4
      at approximately 3.5 years (+/- 6 months) after the initial MCV4 vaccination. Participants
      were then observed for 30 minutes post-injection to monitor for adverse events. Participants
      were also observed at Week 1 for vaccine adverse reactions.

      This portion of the study (Step 3) lasted an additional 24 weeks. There were 4 study visits;
      they occurred at entry, at Days 7-8, and at Weeks 4 and 24. At these visits, a physical exam,
      assessment of HIV-related symptoms, and blood collection occurred. The purpose of this
      follow-up study was to determine the safety and immunogenicity of a MCV4 booster dose in
      HIV-infected participants who have previously received one or two MCV4 vaccinations on this
      study.
    

Intervention name(s): Quadrivalent meningococcal conjugate vaccine
Intervention type(s): Biological
Intervention description(s): MCV4 vaccine (4 µg each of meningococcal A, C, Y, and W-135 polysaccharides conjugated to approximately 48 µg of diphtheria toxoid protein carrier ) was given by injection intramuscularly at least once and no more than three times for each participant, depending on adverse reactions.
Other intervention name(s): MCV4
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Prevention