HIV Infections, Meningitis
Conditions
Brief 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.
Interventions
BIOLOGICALQuadrivalent meningococcal conjugate vaccine
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.
Sponsors
International Maternal Pediatric Adolescent AIDS Clinical Trials Group
National Institute of Allergy and Infectious Diseases (NIAID)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
2 Years to 24 Years
Healthy volunteers
No
Inclusion criteria
for Steps 1, 2, and 3: * HIV-infected * Age greater than or equal to 2 and less than 25 years (Steps 1 and 2 only) * CD4% documented within 120 days of study entry * Participants on antiretroviral therapy (ART) must have been on stable ART regimen for at least 90 days prior to study entry * Able and willing to complete all study immunizations and evaluations * Parent or guardian willing to provide informed consent, if applicable * Participants and/or their partners who are sexually active had to agree to use at least one of the following methods of contraception as long as they are on the study: hormonal birth control drugs (oral, injectable or transdermal); male or female condoms with or without a spermicide; diaphragm/cervical cap with spermicide; intrauterine device (IUD) Inclusion Criteria specific to Step 3: * Participants must have been enrolled in Groups 1 or 3 of previous versions of P1065 * Participants did not have to be less than 25 years of age * Participants must have had serology data from Weeks 0, 4, and 28 from their previous participation in P1065 * Participants must have been within 3.5 years +/- 6 months from the first MCV4 dose received in a previous version of P1065
Exclusion criteria
for Step 1: * Any nonstudy vaccine on study entry day * Any inactive vaccine within 2 weeks prior to study entry * Plans to receive any vaccine 2 weeks after the first injection * Receipt of any live nonstudy vaccine within 4 weeks prior to study entry * Meningococcal conjugate vaccine at any time prior to study entry * Meningococcal polysaccharide vaccine within 2 years prior to study entry * Known hypersensitivity to any component of the MCV4 vaccine, including diphtheria toxoid * Known hypersensitivity to dry natural rubber latex * Life-threatening reaction after previous administration of a vaccine containing similar components * Family history or personal history of Guillain-Barre Syndrome (GBS) * Clinically significant diseases that, in the investigator's opinion, would interfere with the study * Current immunomodulatory therapy, including IL-2, any interferon product, GM-CSF, or thalidomide. Participants taking G-CSF or erythropoietin were not excluded. * Current immunosuppressive therapy, including equivalent of 1 mg/kg/per day or more of prednisone 2 weeks prior to study entry OR planned corticosteroid therapy lasting 2 weeks or longer. Participants using nonsteroidal anti-inflammatory agents and inhaled corticosteroids are not excluded. * Cancer within 12 weeks of study entry * Cancer treatment currently or within 12 weeks of study entry * Loss of strength in lower extremity within 24 weeks prior to study entry * Bleeding disorder or anticoagulant therapy prior to study entry * Absence of ankle and patellar deep tendon reflexes (DTRs) (all four) * Recent receipt of IGIV or any blood or immunoglobulin product (except washed blood cells). More information about this criterion can be found in the protocol. * Other acute or chronic medical or surgical conditions or contraindications that, in the opinion of the investigator, might have interfered with the study * Any new and unresolved Grade 3 or higher laboratory toxicity within 120 days prior to study entry * Any new and unresolved Grade 3 or higher clinical toxicity within 120 days prior to study entry * Pregnancy or breastfeeding
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Primary Response (in Step 3) | Step 3 entry and Week 4 post-booster vaccine | Primary response was defined for each serogroup as a four-fold rise in Ab concentration between day 0 and day 28, but not between day 0 and day 7; OR a change from seronegative on day 0 to seropositive on day 28, but not between day 0 and day 7. Note: a primary response can only occur in the absence of any memory response. |
| Number of Participants With Grade 3 or Higher Adverse Events Within 42 Days Following Dose 1 of the Vaccine. | From administration of Dose 1 at week 0 to 42 days post-vaccination | Adverse events were graded by the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 1.0, dated December, 2004, Clarification August 2009, which is available on the RSC web site (http://rsc.tech-res.com/safetyandpharmacovigilance/). Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 = potentially life-threatening, Grade 5 = death. |
| Number of Participants With Reactions and Grade 3 or Higher Adverse Events Within 42 Days Following Dose 2 of the Vaccine. | From administration of Dose 2 at week 24 to 6 weeks post-vaccination | Adverse events were graded by the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 1.0, dated December, 2004, Clarification August 2009, which is available on the RSC web site (http://rsc.tech-res.com/safetyandpharmacovigilance/). Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 = potentially life-threatening, Grade 5 = death. |
| Number of Participants With Immunogenicity at Step 3 Entry | At 3.5 years (Step 3 entry) | Immunogenicity was assessed for each serogroup by the number of participants with protective antibody levels (titers greater than or equal to 1:128) |
| Number of Participants With 4-fold Memory Response in Step 3 | Step 3 entry and Week 1 post-booster vaccine | Defined for each serogroup as a four-fold rise in antibody titers between booster dose (week 0) and week 1. |
| Number of Participants With Seropositive Memory Response (in Step 3) | Step 3 entry and Week 1 post-booster vaccine | Seropositive memory response was defined for each serogroup by having protective antibody levels (titer \>= 1:128) on Day 0 or change from seronegative to seropositive between booster dose (Day 0) and Day 7. |
| Number of Participants With Immunogenicity at Step 3 Weeks 4 and 24 | At Step 3 Weeks 4 and 24 post-booster vaccine | Immunogenicity was assessed by the number of participants with protective levels of antibody (titers greater than or equal to 1:128) |
| Number of Immunogenic Responders, With Response Defined as a 4-fold or Greater Increase in Serum Bactericidal Antibody Titers From Study Entry to Week 28 After 2 Doses of MCV-4. | Study entry and Week 28 | Serum bactericidal antibody titers were measured at study entry and Week 28 for each of the four serogroups in the MCV-4 vaccine. Response was defined as a 4-fold or greater increase from entry at Week 28. |
| Number of Participants With Short-term Immunogenicity, Defined as Number of Seroconverters at Week 4 (Those With at Least a 4-fold Rise in Meningococcal Serum Bactericidal Titers From Baseline) | At Study entry, Week 4 | Serum bactericidal antibody titers were measured at study entry and Week 4 for each of the four serogroups in the MCV-4 vaccine. Response (seroconversion) was defined as a 4-fold or greater increase from entry at Week 4. |
| Long-term Immunogenicity, as Assessed by Number of Participants With Protective Levels of Antibody at Week 72 | Week 72 | Protective levels of antibody are titers ≥1:128. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Immunologic Memory for Serogroup C by Treatment Arm (1 vs. 2 Doses) | At Week 1 post-booster vaccination | Evidence of immunologic memory according to each of the following definitions: 1. Secondary (anamnestic) response defined as a four-fold rise in Ab titers between day 0 (booster dose) and day 7; or 2. Seroprotection on day 0 or change from titer \<1:128 to titer ≥1:128 (seroprotection) between day 0 and day 7. |
| Immunogenic Response to Serogroup C in Group 2 | At Weeks 4, 28, and 72 | Immunogenic response as assessed by number of participants with protective antibody titers (\>= 1:128) to serogroup C in Group 2 (entry CD4%\<15) |
| Immunologic Memory or Primary Response for Serogroup C by Treatment Arm | At Week 4 post-booster vaccination | Immunologic Memory defined as: 1. Secondary (anamnestic) response defined as a four-fold rise in Ab titers between day 0 (booster dose) and day 7; or 2. Seroprotection on day 0 or change from titer \<1:128 to titer ≥1:128 (seroprotection) between day 0 and day 7. Primary Response defined as: 1. A four-fold rise in Ab concentration between day 0 and day 28, but not between day 0 and day 7; or 2. A change from titer \<1:128 on day 0 to titer ≥1:128on day 28, but not between day 0 and day 7. |
| Safety, as Assessed by Number of Participants With Reactions and Grade 3 or Higher Adverse Events Within 42 Days Following Step 3 Dose of the Vaccine. | From administration of vaccination at Step 3 entry through 6 weeks post-vaccination | Adverse events were graded by the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 1.0, dated December, 2004, Clarification August 2009, which is available on the RSC web site (http://rsc.tech-res.com/safetyandpharmacovigilance/). Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 = potentially life-threatening, Grade 5 = death. |
| Number of Participants With Protective Antibody Titers for Serogroup C at Step 3 Entry | At 3.5 years | Number of participants with protective antibody titers (rSBA\>=1:128) for serogroup C by treatment arm (1 vs. 2 doses) of Group 1 (entry CD4% \>= 15) at Step 3 entry |
Countries
Puerto Rico, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Group 1 (15<CD4%<25) Participants ≥11 to \<25 years with 15\<CD4%\<25 | 127 |
| Group 1 (CD4%≥25) Participants ≥11 to \<25 years with CD4%≥25 | 153 |
| Group 2 Participants ≥11 to \<25 years with CD4%\<15 | 39 |
| Group 3 Participants ≥ 2 to \<11 years with CD4% ≥25 | 59 |
| Total | 378 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Step 3 | Withdrawal by Subject | 3 | 0 | 1 |
| Steps 1 & 2 | Death | 1 | 1 | 0 |
| Steps 1 & 2 | Lost to Follow-up | 5 | 0 | 2 |
| Steps 1 & 2 | Not able to get to clinic | 7 | 4 | 0 |
| Steps 1 & 2 | Not willing to adhere to regulations | 1 | 0 | 0 |
| Steps 1 & 2 | Other eligibility failure | 1 | 1 | 0 |
| Steps 1 & 2 | Withdrawal by Subject | 6 | 1 | 0 |
Baseline characteristics
| Characteristic | Group 1 (CD4%≥25) | Group 1 (15<CD4%<25) | Group 2 | Group 3 | Total |
|---|---|---|---|---|---|
| Age, Continuous | 16 years | 18 years | 20 years | 6 years | 16 years |
| Antiretroviral (ARV) Treatment at Entry HAART with NNRTI (no PI) | 34 participants | 14 participants | 3 participants | 14 participants | 65 participants |
| Antiretroviral (ARV) Treatment at Entry HAART with PI | 81 participants | 70 participants | 22 participants | 38 participants | 211 participants |
| Antiretroviral (ARV) Treatment at Entry No ARV | 30 participants | 37 participants | 13 participants | 6 participants | 86 participants |
| Antiretroviral (ARV) Treatment at Entry Other ARV | 8 participants | 6 participants | 1 participants | 1 participants | 16 participants |
| CDC Classification at Study Entry C | 37 participants | 28 participants | 11 participants | 8 participants | 84 participants |
| CDC Classification at Study Entry Not C | 116 participants | 99 participants | 28 participants | 51 participants | 294 participants |
| Entry plasma HIV RNA viral load, copies/mL <400 copies/mL | 83 participants | 35 participants | 3 participants | 43 participants | 164 participants |
| Entry plasma HIV RNA viral load, copies/mL ≥ 400 copies/mL | 70 participants | 92 participants | 36 participants | 16 participants | 214 participants |
| Ethnicity Hispanic or Latino | 61 participants | 44 participants | 16 participants | 18 participants | 139 participants |
| Ethnicity Not Hispanic or Latino | 89 participants | 83 participants | 23 participants | 40 participants | 235 participants |
| Ethnicity Unknown | 3 participants | 0 participants | 0 participants | 1 participants | 4 participants |
| Race American Indian | 3 participants | 2 participants | 0 participants | 0 participants | 5 participants |
| Race Asian | 1 participants | 1 participants | 0 participants | 2 participants | 4 participants |
| Race Black or African American | 69 participants | 72 participants | 22 participants | 34 participants | 197 participants |
| Race More than One race | 3 participants | 0 participants | 2 participants | 0 participants | 5 participants |
| Race Native Hawaiian or other Pacific islander | 0 participants | 1 participants | 0 participants | 1 participants | 2 participants |
| Race Unknown | 2 participants | 4 participants | 1 participants | 1 participants | 8 participants |
| Race White | 75 participants | 47 participants | 14 participants | 21 participants | 157 participants |
| Screening CD4% | 33.0 percent | 20.0 percent | 8.5 percent | 36.0 percent | 27.9 percent |
| Sex: Female, Male Female | 70 Participants | 44 Participants | 16 Participants | 31 Participants | 161 Participants |
| Sex: Female, Male Male | 83 Participants | 83 Participants | 23 Participants | 28 Participants | 217 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 94 / 127 | 113 / 153 | 33 / 39 | 47 / 59 |
| serious Total, serious adverse events | 4 / 127 | 5 / 153 | 5 / 39 | 2 / 59 |
Outcome results
Primary
Long-term Immunogenicity, as Assessed by Number of Participants With Protective Levels of Antibody at Week 72
Protective levels of antibody are titers ≥1:128.
Time frame: Week 72
Population: Participants with antibody data at Week 72. The number of Participants analyzed for Group 1 (15\<CD4%\<25), Group 1 (CD4%≥25), Group 2, Group 3 respectively are:~serogroup A are 82, 108, 18, 44 serogroup C are 78, 110, 16, 44 serogroup W-135 are 80, 110, 17, 44 serogroup Y are 82, 110, 18, 44
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Group 1 (15<CD4%<25) | Long-term Immunogenicity, as Assessed by Number of Participants With Protective Levels of Antibody at Week 72 | Week 72 Responders, serogroup A | 39 participants |
| Group 1 (15<CD4%<25) | Long-term Immunogenicity, as Assessed by Number of Participants With Protective Levels of Antibody at Week 72 | Week 72 Responders, serogroup C | 17 participants |
| Group 1 (15<CD4%<25) | Long-term Immunogenicity, as Assessed by Number of Participants With Protective Levels of Antibody at Week 72 | Week 72 Responders, serogroup W-135 | 36 participants |
| Group 1 (15<CD4%<25) | Long-term Immunogenicity, as Assessed by Number of Participants With Protective Levels of Antibody at Week 72 | Week 72 Responders, serogroup Y | 49 participants |
| Group 1 (CD4%≥25) | Long-term Immunogenicity, as Assessed by Number of Participants With Protective Levels of Antibody at Week 72 | Week 72 Responders, serogroup C | 36 participants |
| Group 1 (CD4%≥25) | Long-term Immunogenicity, as Assessed by Number of Participants With Protective Levels of Antibody at Week 72 | Week 72 Responders, serogroup W-135 | 83 participants |
| Group 1 (CD4%≥25) | Long-term Immunogenicity, as Assessed by Number of Participants With Protective Levels of Antibody at Week 72 | Week 72 Responders, serogroup Y | 80 participants |
| Group 1 (CD4%≥25) | Long-term Immunogenicity, as Assessed by Number of Participants With Protective Levels of Antibody at Week 72 | Week 72 Responders, serogroup A | 82 participants |
| Group 2 | Long-term Immunogenicity, as Assessed by Number of Participants With Protective Levels of Antibody at Week 72 | Week 72 Responders, serogroup W-135 | 6 participants |
| Group 2 | Long-term Immunogenicity, as Assessed by Number of Participants With Protective Levels of Antibody at Week 72 | Week 72 Responders, serogroup C | 1 participants |
| Group 2 | Long-term Immunogenicity, as Assessed by Number of Participants With Protective Levels of Antibody at Week 72 | Week 72 Responders, serogroup Y | 5 participants |
| Group 2 | Long-term Immunogenicity, as Assessed by Number of Participants With Protective Levels of Antibody at Week 72 | Week 72 Responders, serogroup A | 4 participants |
| Group 3 | Long-term Immunogenicity, as Assessed by Number of Participants With Protective Levels of Antibody at Week 72 | Week 72 Responders, serogroup Y | 40 participants |
| Group 3 | Long-term Immunogenicity, as Assessed by Number of Participants With Protective Levels of Antibody at Week 72 | Week 72 Responders, serogroup C | 20 participants |
| Group 3 | Long-term Immunogenicity, as Assessed by Number of Participants With Protective Levels of Antibody at Week 72 | Week 72 Responders, serogroup A | 35 participants |
| Group 3 | Long-term Immunogenicity, as Assessed by Number of Participants With Protective Levels of Antibody at Week 72 | Week 72 Responders, serogroup W-135 | 42 participants |
Primary
Number of Immunogenic Responders, With Response Defined as a 4-fold or Greater Increase in Serum Bactericidal Antibody Titers From Study Entry to Week 28 After 2 Doses of MCV-4.
Serum bactericidal antibody titers were measured at study entry and Week 28 for each of the four serogroups in the MCV-4 vaccine. Response was defined as a 4-fold or greater increase from entry at Week 28.
Time frame: Study entry and Week 28
Population: This outcome only includes participants who received 2 doses and had antibody data from both entry and Week 28.The number of participants analyzed for Group 1 (15\<CD4%\<25), Group 1 (CD4%≥25), Group 2, Group 3 are respectively:~serogroup A: 49, 63, 20, 49 serogroup C: 47, 65, 18, 49 serogroup W-135: 47, 66, 19, 49 serogroup Y: 49, 66, 19, 49
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Group 1 (15<CD4%<25) | Number of Immunogenic Responders, With Response Defined as a 4-fold or Greater Increase in Serum Bactericidal Antibody Titers From Study Entry to Week 28 After 2 Doses of MCV-4. | Week 28 reponders, serogroup W-135 | 36 participants |
| Group 1 (15<CD4%<25) | Number of Immunogenic Responders, With Response Defined as a 4-fold or Greater Increase in Serum Bactericidal Antibody Titers From Study Entry to Week 28 After 2 Doses of MCV-4. | Week 28 reponders, serogroup Y | 32 participants |
| Group 1 (15<CD4%<25) | Number of Immunogenic Responders, With Response Defined as a 4-fold or Greater Increase in Serum Bactericidal Antibody Titers From Study Entry to Week 28 After 2 Doses of MCV-4. | Week 28 reponders, serogroup C | 28 participants |
| Group 1 (15<CD4%<25) | Number of Immunogenic Responders, With Response Defined as a 4-fold or Greater Increase in Serum Bactericidal Antibody Titers From Study Entry to Week 28 After 2 Doses of MCV-4. | Week 28 reponders, serogroup A | 27 participants |
| Group 1 (CD4%≥25) | Number of Immunogenic Responders, With Response Defined as a 4-fold or Greater Increase in Serum Bactericidal Antibody Titers From Study Entry to Week 28 After 2 Doses of MCV-4. | Week 28 reponders, serogroup C | 49 participants |
| Group 1 (CD4%≥25) | Number of Immunogenic Responders, With Response Defined as a 4-fold or Greater Increase in Serum Bactericidal Antibody Titers From Study Entry to Week 28 After 2 Doses of MCV-4. | Week 28 reponders, serogroup W-135 | 61 participants |
| Group 1 (CD4%≥25) | Number of Immunogenic Responders, With Response Defined as a 4-fold or Greater Increase in Serum Bactericidal Antibody Titers From Study Entry to Week 28 After 2 Doses of MCV-4. | Week 28 reponders, serogroup A | 60 participants |
| Group 1 (CD4%≥25) | Number of Immunogenic Responders, With Response Defined as a 4-fold or Greater Increase in Serum Bactericidal Antibody Titers From Study Entry to Week 28 After 2 Doses of MCV-4. | Week 28 reponders, serogroup Y | 54 participants |
| Group 2 | Number of Immunogenic Responders, With Response Defined as a 4-fold or Greater Increase in Serum Bactericidal Antibody Titers From Study Entry to Week 28 After 2 Doses of MCV-4. | Week 28 reponders, serogroup C | 1 participants |
| Group 2 | Number of Immunogenic Responders, With Response Defined as a 4-fold or Greater Increase in Serum Bactericidal Antibody Titers From Study Entry to Week 28 After 2 Doses of MCV-4. | Week 28 reponders, serogroup A | 8 participants |
| Group 2 | Number of Immunogenic Responders, With Response Defined as a 4-fold or Greater Increase in Serum Bactericidal Antibody Titers From Study Entry to Week 28 After 2 Doses of MCV-4. | Week 28 reponders, serogroup Y | 1 participants |
| Group 2 | Number of Immunogenic Responders, With Response Defined as a 4-fold or Greater Increase in Serum Bactericidal Antibody Titers From Study Entry to Week 28 After 2 Doses of MCV-4. | Week 28 reponders, serogroup W-135 | 0 participants |
| Group 3 | Number of Immunogenic Responders, With Response Defined as a 4-fold or Greater Increase in Serum Bactericidal Antibody Titers From Study Entry to Week 28 After 2 Doses of MCV-4. | Week 28 reponders, serogroup Y | 41 participants |
| Group 3 | Number of Immunogenic Responders, With Response Defined as a 4-fold or Greater Increase in Serum Bactericidal Antibody Titers From Study Entry to Week 28 After 2 Doses of MCV-4. | Week 28 reponders, serogroup W-135 | 49 participants |
| Group 3 | Number of Immunogenic Responders, With Response Defined as a 4-fold or Greater Increase in Serum Bactericidal Antibody Titers From Study Entry to Week 28 After 2 Doses of MCV-4. | Week 28 reponders, serogroup A | 43 participants |
| Group 3 | Number of Immunogenic Responders, With Response Defined as a 4-fold or Greater Increase in Serum Bactericidal Antibody Titers From Study Entry to Week 28 After 2 Doses of MCV-4. | Week 28 reponders, serogroup C | 39 participants |
Primary
Number of Participants With 4-fold Memory Response in Step 3
Defined for each serogroup as a four-fold rise in antibody titers between booster dose (week 0) and week 1.
Time frame: Step 3 entry and Week 1 post-booster vaccine
Population: Because response is a combination of memory and primary response, only participants with data for weeks 0, 1 and 4 are included.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Group 1 (15<CD4%<25) | Number of Participants With 4-fold Memory Response in Step 3 | 4-fold memory responders, serogroup A | 54 participants |
| Group 1 (15<CD4%<25) | Number of Participants With 4-fold Memory Response in Step 3 | 4-fold memory responders, serogroup C | 56 participants |
| Group 1 (15<CD4%<25) | Number of Participants With 4-fold Memory Response in Step 3 | 4-fold memory responders, serogroup W-135 | 63 participants |
| Group 1 (15<CD4%<25) | Number of Participants With 4-fold Memory Response in Step 3 | 4-fold memory responders, serogroup Y | 54 participants |
| Group 1 (CD4%≥25) | Number of Participants With 4-fold Memory Response in Step 3 | 4-fold memory responders, serogroup C | 50 participants |
| Group 1 (CD4%≥25) | Number of Participants With 4-fold Memory Response in Step 3 | 4-fold memory responders, serogroup Y | 51 participants |
| Group 1 (CD4%≥25) | Number of Participants With 4-fold Memory Response in Step 3 | 4-fold memory responders, serogroup A | 49 participants |
| Group 1 (CD4%≥25) | Number of Participants With 4-fold Memory Response in Step 3 | 4-fold memory responders, serogroup W-135 | 55 participants |
| Group 2 | Number of Participants With 4-fold Memory Response in Step 3 | 4-fold memory responders, serogroup W-135 | 33 participants |
| Group 2 | Number of Participants With 4-fold Memory Response in Step 3 | 4-fold memory responders, serogroup C | 34 participants |
| Group 2 | Number of Participants With 4-fold Memory Response in Step 3 | 4-fold memory responders, serogroup A | 33 participants |
| Group 2 | Number of Participants With 4-fold Memory Response in Step 3 | 4-fold memory responders, serogroup Y | 33 participants |
Primary
Number of Participants With Grade 3 or Higher Adverse Events Within 42 Days Following Dose 1 of the Vaccine.
Adverse events were graded by the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 1.0, dated December, 2004, Clarification August 2009, which is available on the RSC web site (http://rsc.tech-res.com/safetyandpharmacovigilance/). Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 = potentially life-threatening, Grade 5 = death.
Time frame: From administration of Dose 1 at week 0 to 42 days post-vaccination
Population: All participants who received Dose 1.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group 1 (15<CD4%<25) | Number of Participants With Grade 3 or Higher Adverse Events Within 42 Days Following Dose 1 of the Vaccine. | 3 participants |
| Group 1 (CD4%≥25) | Number of Participants With Grade 3 or Higher Adverse Events Within 42 Days Following Dose 1 of the Vaccine. | 1 participants |
| Group 2 | Number of Participants With Grade 3 or Higher Adverse Events Within 42 Days Following Dose 1 of the Vaccine. | 3 participants |
| Group 3 | Number of Participants With Grade 3 or Higher Adverse Events Within 42 Days Following Dose 1 of the Vaccine. | 0 participants |
Comparison: The null hypothesis was that there would be no difference between CD4% strata.p-value: 0.03Fisher Exact
Primary
Number of Participants With Immunogenicity at Step 3 Entry
Immunogenicity was assessed for each serogroup by the number of participants with protective antibody levels (titers greater than or equal to 1:128)
Time frame: At 3.5 years (Step 3 entry)
Population: All participants who had antibody data for Step 3 Week 0
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Group 1 (15<CD4%<25) | Number of Participants With Immunogenicity at Step 3 Entry | Immunogenicity, Serogroup W-135 | 30 participants |
| Group 1 (15<CD4%<25) | Number of Participants With Immunogenicity at Step 3 Entry | Immunogenicity, Serogroup A | 47 participants |
| Group 1 (15<CD4%<25) | Number of Participants With Immunogenicity at Step 3 Entry | Immunogenicity, Serogroup Y | 39 participants |
| Group 1 (15<CD4%<25) | Number of Participants With Immunogenicity at Step 3 Entry | Immunogenicity, Serogroup C | 19 participants |
| Group 1 (CD4%≥25) | Number of Participants With Immunogenicity at Step 3 Entry | Immunogenicity, Serogroup W-135 | 35 participants |
| Group 1 (CD4%≥25) | Number of Participants With Immunogenicity at Step 3 Entry | Immunogenicity, Serogroup C | 20 participants |
| Group 1 (CD4%≥25) | Number of Participants With Immunogenicity at Step 3 Entry | Immunogenicity, Serogroup A | 48 participants |
| Group 1 (CD4%≥25) | Number of Participants With Immunogenicity at Step 3 Entry | Immunogenicity, Serogroup Y | 33 participants |
| Group 2 | Number of Participants With Immunogenicity at Step 3 Entry | Immunogenicity, Serogroup C | 9 participants |
| Group 2 | Number of Participants With Immunogenicity at Step 3 Entry | Immunogenicity, Serogroup A | 34 participants |
| Group 2 | Number of Participants With Immunogenicity at Step 3 Entry | Immunogenicity, Serogroup Y | 24 participants |
| Group 2 | Number of Participants With Immunogenicity at Step 3 Entry | Immunogenicity, Serogroup W-135 | 23 participants |
Primary
Number of Participants With Immunogenicity at Step 3 Weeks 4 and 24
Immunogenicity was assessed by the number of participants with protective levels of antibody (titers greater than or equal to 1:128)
Time frame: At Step 3 Weeks 4 and 24 post-booster vaccine
Population: Participants with data for Step 3 weeks 4 and 24. The numbers for Group 1 (1-dose), Group 1 (2-dose), and Group 3 respectively are:~Week 4: 73, 71, 37 Week 24: 73, 70, 33
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Group 1 (15<CD4%<25) | Number of Participants With Immunogenicity at Step 3 Weeks 4 and 24 | Week 4 immunogenicity, serogroup Y | 67 participants |
| Group 1 (15<CD4%<25) | Number of Participants With Immunogenicity at Step 3 Weeks 4 and 24 | Week 24 immunogenicity, serogroup W-135 | 57 participants |
| Group 1 (15<CD4%<25) | Number of Participants With Immunogenicity at Step 3 Weeks 4 and 24 | Week 4 immunogenicity, serogroup A | 66 participants |
| Group 1 (15<CD4%<25) | Number of Participants With Immunogenicity at Step 3 Weeks 4 and 24 | Week 24 immunogenicity, serogroup C | 41 participants |
| Group 1 (15<CD4%<25) | Number of Participants With Immunogenicity at Step 3 Weeks 4 and 24 | Week 24 immunogenicity, serogroup Y | 58 participants |
| Group 1 (15<CD4%<25) | Number of Participants With Immunogenicity at Step 3 Weeks 4 and 24 | Week 4 immunogenicity, serogroup W-135 | 67 participants |
| Group 1 (15<CD4%<25) | Number of Participants With Immunogenicity at Step 3 Weeks 4 and 24 | Week 24 immunogenicity, serogroup A | 58 participants |
| Group 1 (15<CD4%<25) | Number of Participants With Immunogenicity at Step 3 Weeks 4 and 24 | Week 4 immunogenicity, serogroup C | 61 participants |
| Group 1 (CD4%≥25) | Number of Participants With Immunogenicity at Step 3 Weeks 4 and 24 | Week 4 immunogenicity, serogroup A | 67 participants |
| Group 1 (CD4%≥25) | Number of Participants With Immunogenicity at Step 3 Weeks 4 and 24 | Week 4 immunogenicity, serogroup C | 60 participants |
| Group 1 (CD4%≥25) | Number of Participants With Immunogenicity at Step 3 Weeks 4 and 24 | Week 24 immunogenicity, serogroup A | 59 participants |
| Group 1 (CD4%≥25) | Number of Participants With Immunogenicity at Step 3 Weeks 4 and 24 | Week 24 immunogenicity, serogroup C | 46 participants |
| Group 1 (CD4%≥25) | Number of Participants With Immunogenicity at Step 3 Weeks 4 and 24 | Week 24 immunogenicity, serogroup W-135 | 53 participants |
| Group 1 (CD4%≥25) | Number of Participants With Immunogenicity at Step 3 Weeks 4 and 24 | Week 4 immunogenicity, serogroup W-135 | 64 participants |
| Group 1 (CD4%≥25) | Number of Participants With Immunogenicity at Step 3 Weeks 4 and 24 | Week 4 immunogenicity, serogroup Y | 62 participants |
| Group 1 (CD4%≥25) | Number of Participants With Immunogenicity at Step 3 Weeks 4 and 24 | Week 24 immunogenicity, serogroup Y | 52 participants |
| Group 2 | Number of Participants With Immunogenicity at Step 3 Weeks 4 and 24 | Week 4 immunogenicity, serogroup C | 35 participants |
| Group 2 | Number of Participants With Immunogenicity at Step 3 Weeks 4 and 24 | Week 4 immunogenicity, serogroup W-135 | 37 participants |
| Group 2 | Number of Participants With Immunogenicity at Step 3 Weeks 4 and 24 | Week 24 immunogenicity, serogroup A | 30 participants |
| Group 2 | Number of Participants With Immunogenicity at Step 3 Weeks 4 and 24 | Week 4 immunogenicity, serogroup A | 37 participants |
| Group 2 | Number of Participants With Immunogenicity at Step 3 Weeks 4 and 24 | Week 4 immunogenicity, serogroup Y | 35 participants |
| Group 2 | Number of Participants With Immunogenicity at Step 3 Weeks 4 and 24 | Week 24 immunogenicity, serogroup W-135 | 32 participants |
| Group 2 | Number of Participants With Immunogenicity at Step 3 Weeks 4 and 24 | Week 24 immunogenicity, serogroup Y | 31 participants |
| Group 2 | Number of Participants With Immunogenicity at Step 3 Weeks 4 and 24 | Week 24 immunogenicity, serogroup C | 24 participants |
Primary
Number of Participants With Primary Response (in Step 3)
Primary response was defined for each serogroup as a four-fold rise in Ab concentration between day 0 and day 28, but not between day 0 and day 7; OR a change from seronegative on day 0 to seropositive on day 28, but not between day 0 and day 7. Note: a primary response can only occur in the absence of any memory response.
Time frame: Step 3 entry and Week 4 post-booster vaccine
Population: Because response is a combination of memory and primary response, only participants with data for weeks 0, 1 and 4 are included.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Group 1 (15<CD4%<25) | Number of Participants With Primary Response (in Step 3) | Primary responder, serogroup A | 2 participants |
| Group 1 (15<CD4%<25) | Number of Participants With Primary Response (in Step 3) | Primary responder, serogroup C | 1 participants |
| Group 1 (15<CD4%<25) | Number of Participants With Primary Response (in Step 3) | Primary responder, serogroup W-135 | 1 participants |
| Group 1 (15<CD4%<25) | Number of Participants With Primary Response (in Step 3) | Primary responder, serogroup Y | 1 participants |
| Group 1 (CD4%≥25) | Number of Participants With Primary Response (in Step 3) | Primary responder, serogroup Y | 2 participants |
| Group 1 (CD4%≥25) | Number of Participants With Primary Response (in Step 3) | Primary responder, serogroup A | 2 participants |
| Group 1 (CD4%≥25) | Number of Participants With Primary Response (in Step 3) | Primary responder, serogroup W-135 | 0 participants |
| Group 1 (CD4%≥25) | Number of Participants With Primary Response (in Step 3) | Primary responder, serogroup C | 1 participants |
| Group 2 | Number of Participants With Primary Response (in Step 3) | Primary responder, serogroup Y | 2 participants |
| Group 2 | Number of Participants With Primary Response (in Step 3) | Primary responder, serogroup C | 1 participants |
| Group 2 | Number of Participants With Primary Response (in Step 3) | Primary responder, serogroup W-135 | 2 participants |
| Group 2 | Number of Participants With Primary Response (in Step 3) | Primary responder, serogroup A | 0 participants |
Primary
Number of Participants With Reactions and Grade 3 or Higher Adverse Events Within 42 Days Following Dose 2 of the Vaccine.
Adverse events were graded by the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 1.0, dated December, 2004, Clarification August 2009, which is available on the RSC web site (http://rsc.tech-res.com/safetyandpharmacovigilance/). Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 = potentially life-threatening, Grade 5 = death.
Time frame: From administration of Dose 2 at week 24 to 6 weeks post-vaccination
Population: All participants who entered Step 2
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group 1 (15<CD4%<25) | Number of Participants With Reactions and Grade 3 or Higher Adverse Events Within 42 Days Following Dose 2 of the Vaccine. | 0 participants |
| Group 1 (CD4%≥25) | Number of Participants With Reactions and Grade 3 or Higher Adverse Events Within 42 Days Following Dose 2 of the Vaccine. | 0 participants |
| Group 2 | Number of Participants With Reactions and Grade 3 or Higher Adverse Events Within 42 Days Following Dose 2 of the Vaccine. | 2 participants |
| Group 3 | Number of Participants With Reactions and Grade 3 or Higher Adverse Events Within 42 Days Following Dose 2 of the Vaccine. | 0 participants |
Comparison: The null hypothesis was that there were no differences between CD4% strata.p-value: 0.01Fisher Exact
Primary
Number of Participants With Seropositive Memory Response (in Step 3)
Seropositive memory response was defined for each serogroup by having protective antibody levels (titer \>= 1:128) on Day 0 or change from seronegative to seropositive between booster dose (Day 0) and Day 7.
Time frame: Step 3 entry and Week 1 post-booster vaccine
Population: Because response is a combination of memory and primary response, only participants with data for weeks 0, 1 and 4 are included.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Group 1 (15<CD4%<25) | Number of Participants With Seropositive Memory Response (in Step 3) | Seropositive memory responder, serogroup C | 62 participants |
| Group 1 (15<CD4%<25) | Number of Participants With Seropositive Memory Response (in Step 3) | Seropositive memory responder, serogroup W-135 | 65 participants |
| Group 1 (15<CD4%<25) | Number of Participants With Seropositive Memory Response (in Step 3) | Seropositive memory responder, serogroup A | 65 participants |
| Group 1 (15<CD4%<25) | Number of Participants With Seropositive Memory Response (in Step 3) | Seropositive memory responder, serogroup Y | 67 participants |
| Group 1 (CD4%≥25) | Number of Participants With Seropositive Memory Response (in Step 3) | Seropositive memory responder, serogroup Y | 57 participants |
| Group 1 (CD4%≥25) | Number of Participants With Seropositive Memory Response (in Step 3) | Seropositive memory responder, serogroup A | 61 participants |
| Group 1 (CD4%≥25) | Number of Participants With Seropositive Memory Response (in Step 3) | Seropositive memory responder, serogroup W-135 | 60 participants |
| Group 1 (CD4%≥25) | Number of Participants With Seropositive Memory Response (in Step 3) | Seropositive memory responder, serogroup C | 55 participants |
| Group 2 | Number of Participants With Seropositive Memory Response (in Step 3) | Seropositive memory responder, serogroup W-135 | 34 participants |
| Group 2 | Number of Participants With Seropositive Memory Response (in Step 3) | Seropositive memory responder, serogroup Y | 33 participants |
| Group 2 | Number of Participants With Seropositive Memory Response (in Step 3) | Seropositive memory responder, serogroup A | 35 participants |
| Group 2 | Number of Participants With Seropositive Memory Response (in Step 3) | Seropositive memory responder, serogroup C | 34 participants |
Primary
Number of Participants With Short-term Immunogenicity, Defined as Number of Seroconverters at Week 4 (Those With at Least a 4-fold Rise in Meningococcal Serum Bactericidal Titers From Baseline)
Serum bactericidal antibody titers were measured at study entry and Week 4 for each of the four serogroups in the MCV-4 vaccine. Response (seroconversion) was defined as a 4-fold or greater increase from entry at Week 4.
Time frame: At Study entry, Week 4
Population: This outcome only includes participants who had antibody data from both entry and Week 4.The number of participants analyzed for Group 1 (15\<CD4%\<25), Group 1 (CD4%≥25), Group 2, Group 3 respectively are:~serogroup A are 93, 129, 20, 49 serogroup C are 90, 130, 18, 49 serogroup W-135 are 91, 131, 19, 49 serogroup Y are 93, 131, 20, 49
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Group 1 (15<CD4%<25) | Number of Participants With Short-term Immunogenicity, Defined as Number of Seroconverters at Week 4 (Those With at Least a 4-fold Rise in Meningococcal Serum Bactericidal Titers From Baseline) | Week 4 Seroconverters, serogroup C | 44 participants |
| Group 1 (15<CD4%<25) | Number of Participants With Short-term Immunogenicity, Defined as Number of Seroconverters at Week 4 (Those With at Least a 4-fold Rise in Meningococcal Serum Bactericidal Titers From Baseline) | Week 4 Seroconverters, serogroup W-135 | 66 participants |
| Group 1 (15<CD4%<25) | Number of Participants With Short-term Immunogenicity, Defined as Number of Seroconverters at Week 4 (Those With at Least a 4-fold Rise in Meningococcal Serum Bactericidal Titers From Baseline) | Week 4 Seroconverters, serogroup A | 61 participants |
| Group 1 (15<CD4%<25) | Number of Participants With Short-term Immunogenicity, Defined as Number of Seroconverters at Week 4 (Those With at Least a 4-fold Rise in Meningococcal Serum Bactericidal Titers From Baseline) | Week 4 Seroconverters, serogroup Y | 49 participants |
| Group 1 (CD4%≥25) | Number of Participants With Short-term Immunogenicity, Defined as Number of Seroconverters at Week 4 (Those With at Least a 4-fold Rise in Meningococcal Serum Bactericidal Titers From Baseline) | Week 4 Seroconverters, serogroup C | 89 participants |
| Group 1 (CD4%≥25) | Number of Participants With Short-term Immunogenicity, Defined as Number of Seroconverters at Week 4 (Those With at Least a 4-fold Rise in Meningococcal Serum Bactericidal Titers From Baseline) | Week 4 Seroconverters, serogroup W-135 | 118 participants |
| Group 1 (CD4%≥25) | Number of Participants With Short-term Immunogenicity, Defined as Number of Seroconverters at Week 4 (Those With at Least a 4-fold Rise in Meningococcal Serum Bactericidal Titers From Baseline) | Week 4 Seroconverters, serogroup Y | 100 participants |
| Group 1 (CD4%≥25) | Number of Participants With Short-term Immunogenicity, Defined as Number of Seroconverters at Week 4 (Those With at Least a 4-fold Rise in Meningococcal Serum Bactericidal Titers From Baseline) | Week 4 Seroconverters, serogroup A | 107 participants |
| Group 2 | Number of Participants With Short-term Immunogenicity, Defined as Number of Seroconverters at Week 4 (Those With at Least a 4-fold Rise in Meningococcal Serum Bactericidal Titers From Baseline) | Week 4 Seroconverters, serogroup A | 5 participants |
| Group 2 | Number of Participants With Short-term Immunogenicity, Defined as Number of Seroconverters at Week 4 (Those With at Least a 4-fold Rise in Meningococcal Serum Bactericidal Titers From Baseline) | Week 4 Seroconverters, serogroup Y | 8 participants |
| Group 2 | Number of Participants With Short-term Immunogenicity, Defined as Number of Seroconverters at Week 4 (Those With at Least a 4-fold Rise in Meningococcal Serum Bactericidal Titers From Baseline) | Week 4 Seroconverters, serogroup W-135 | 6 participants |
| Group 2 | Number of Participants With Short-term Immunogenicity, Defined as Number of Seroconverters at Week 4 (Those With at Least a 4-fold Rise in Meningococcal Serum Bactericidal Titers From Baseline) | Week 4 Seroconverters, serogroup C | 3 participants |
| Group 3 | Number of Participants With Short-term Immunogenicity, Defined as Number of Seroconverters at Week 4 (Those With at Least a 4-fold Rise in Meningococcal Serum Bactericidal Titers From Baseline) | Week 4 Seroconverters, serogroup Y | 37 participants |
| Group 3 | Number of Participants With Short-term Immunogenicity, Defined as Number of Seroconverters at Week 4 (Those With at Least a 4-fold Rise in Meningococcal Serum Bactericidal Titers From Baseline) | Week 4 Seroconverters, serogroup A | 45 participants |
| Group 3 | Number of Participants With Short-term Immunogenicity, Defined as Number of Seroconverters at Week 4 (Those With at Least a 4-fold Rise in Meningococcal Serum Bactericidal Titers From Baseline) | Week 4 Seroconverters, serogroup W-135 | 48 participants |
| Group 3 | Number of Participants With Short-term Immunogenicity, Defined as Number of Seroconverters at Week 4 (Those With at Least a 4-fold Rise in Meningococcal Serum Bactericidal Titers From Baseline) | Week 4 Seroconverters, serogroup C | 21 participants |
Secondary
Immunogenic Response to Serogroup C in Group 2
Immunogenic response as assessed by number of participants with protective antibody titers (\>= 1:128) to serogroup C in Group 2 (entry CD4%\<15)
Time frame: At Weeks 4, 28, and 72
Population: Group 2 participants with response data for weeks 4, 28 and 72
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group 1 (15<CD4%<25) | Immunogenic Response to Serogroup C in Group 2 | 4 participants |
| Group 1 (CD4%≥25) | Immunogenic Response to Serogroup C in Group 2 | 4 participants |
| Group 2 | Immunogenic Response to Serogroup C in Group 2 | 1 participants |
Secondary
Immunologic Memory for Serogroup C by Treatment Arm (1 vs. 2 Doses)
Evidence of immunologic memory according to each of the following definitions: 1. Secondary (anamnestic) response defined as a four-fold rise in Ab titers between day 0 (booster dose) and day 7; or 2. Seroprotection on day 0 or change from titer \<1:128 to titer ≥1:128 (seroprotection) between day 0 and day 7.
Time frame: At Week 1 post-booster vaccination
Population: Participants in Group 1 who entered Step 3
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group 1 (15<CD4%<25) | Immunologic Memory for Serogroup C by Treatment Arm (1 vs. 2 Doses) | 65 participants |
| Group 1 (CD4%≥25) | Immunologic Memory for Serogroup C by Treatment Arm (1 vs. 2 Doses) | 61 participants |
Secondary
Immunologic Memory or Primary Response for Serogroup C by Treatment Arm
Immunologic Memory defined as: 1. Secondary (anamnestic) response defined as a four-fold rise in Ab titers between day 0 (booster dose) and day 7; or 2. Seroprotection on day 0 or change from titer \<1:128 to titer ≥1:128 (seroprotection) between day 0 and day 7. Primary Response defined as: 1. A four-fold rise in Ab concentration between day 0 and day 28, but not between day 0 and day 7; or 2. A change from titer \<1:128 on day 0 to titer ≥1:128on day 28, but not between day 0 and day 7.
Time frame: At Week 4 post-booster vaccination
Population: Group 1 participants who entered Step 3
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group 1 (15<CD4%<25) | Immunologic Memory or Primary Response for Serogroup C by Treatment Arm | 64 participants |
| Group 1 (CD4%≥25) | Immunologic Memory or Primary Response for Serogroup C by Treatment Arm | 57 participants |
Secondary
Number of Participants With Protective Antibody Titers for Serogroup C at Step 3 Entry
Number of participants with protective antibody titers (rSBA\>=1:128) for serogroup C by treatment arm (1 vs. 2 doses) of Group 1 (entry CD4% \>= 15) at Step 3 entry
Time frame: At 3.5 years
Population: Group 1 and 3 participants at entry to Step 3
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group 1 (15<CD4%<25) | Number of Participants With Protective Antibody Titers for Serogroup C at Step 3 Entry | 19 participants |
| Group 1 (CD4%≥25) | Number of Participants With Protective Antibody Titers for Serogroup C at Step 3 Entry | 17 participants |
| Group 2 | Number of Participants With Protective Antibody Titers for Serogroup C at Step 3 Entry | 3 participants |
| Group 3 | Number of Participants With Protective Antibody Titers for Serogroup C at Step 3 Entry | 6 participants |
Secondary
Safety, as Assessed by Number of Participants With Reactions and Grade 3 or Higher Adverse Events Within 42 Days Following Step 3 Dose of the Vaccine.
Adverse events were graded by the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 1.0, dated December, 2004, Clarification August 2009, which is available on the RSC web site (http://rsc.tech-res.com/safetyandpharmacovigilance/). Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 = potentially life-threatening, Grade 5 = death.
Time frame: From administration of vaccination at Step 3 entry through 6 weeks post-vaccination
Population: All participants who were vaccinated at Step 3 entry
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group 1 (15<CD4%<25) | Safety, as Assessed by Number of Participants With Reactions and Grade 3 or Higher Adverse Events Within 42 Days Following Step 3 Dose of the Vaccine. | 2 participants |
| Group 1 (CD4%≥25) | Safety, as Assessed by Number of Participants With Reactions and Grade 3 or Higher Adverse Events Within 42 Days Following Step 3 Dose of the Vaccine. | 0 participants |