Safety of and Immune Response to a Pneumococcal Vaccine (PncCV) in HIV Infected and Uninfected Children

Study Overview
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Brief Summary
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Infection by Streptococcal pneumoniae is a common invasive bacterial infection in HIV infected children. The purpose of this study is to determine the safety of and immune response to a pneumococcal polysaccharide-protein conjugate vaccine (PncCV) in HIV infected and uninfected children. The study will also determine the safety of and immune response to Haemophilus influenzae vaccine (HibCV) in these children. Recruitment for this study will occur at two hospitals in South Africa, and all HIV infected infants participating in this study must also be coenrolled in the CIPRA SA-Project 2 study.

Detailed Description
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HIV infected children are at high risk for invasive pneumococcal disease (IPD) caused by the bacterium Streptococcus pneumoniae. Chemoprophylaxis has been used in children with certain diseases for the prevention of IPD, but drug resistance may develop with this prevention strategy. In contrast, a vaccine to prevent IPD would have fewer negative implications on future treatment options than chemoprophylaxis. This study will evaluate the safety of and immune response to PncCV in South African HIV infected and uninfected children. This study will also evaluate the safety of and immune response to HibCV in these children. This study will last 5.5 years. There will be 5 groups in this study. Group 1 will be HIV uninfected infants born to HIV uninfected mothers. Group 2 will be HIV infected infants in CDC Disease Category 1 who were randomly assigned to the delayed therapy arm (Arm 1) of CIPRA SA-Project 2. Group 3 will be HIV infected infants in CDC Disease Category 1 who were randomly assigned to the first early therapy arm (Arm 2) of CIPRA SA-Project 2. Group 4 will be HIV infected infants in CDC Disease Category 2 or 3 who were randomly assigned to the second early therapy arm (Arm 3) of CIPRA SA-Project 2. Group 5 will be HIV uninfected infants born to HIV infected mothers; Group 5 infants will undergo repeat HIV testing at 4 to 8 months of age, 9 to 11 months of age, and approximately 18 months of age. There will be 13 study visits; medical history assessment, a physical examination, and blood collection will occur at each visit. At each of 3 study visits before age 24 weeks, all participants will receive an injection of PncCV and an injection of routine pediatric vaccines, including HibCV. Previously vaccinated HIV infected participants will only receive those vaccines they need to complete the South African series of routine pediatric vaccinations. Within each group, participants will be randomly assigned to receive a booster shot of either PncCV or HibCV between 64 and 76 weeks of age. Participants will also receive two measles vaccinations between 38 and 76 weeks of age. Parents or guardians will be asked to complete a diary card after each vaccination and report any adverse effects occurring within the 72 hours post-vaccination.

Official Title
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Evaluation of Quantitative and Qualitative Antibody Responses to Streptococcus Pneumoniae and Haemophilus Influenzae Type b Conjugate Vaccines Amongst HIV-1-Exposed-Infected Children That Are Receiving Vs. Those Not Receiving Antiretroviral Therapy, as Well as Among HIV-1-Exposed-Uninfected Children and HIV-1-Unexposed-Uninfected Children

Conditions
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HIV Infections, Pneumococcal Infections

Intervention / Treatment
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* Biological: Pneumococcal polysaccharide-protein conjugate vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria for All Infants: Birth weight of at least 2 kg (4.4 lbs) Written informed consent from parent or guardian Mother's HIV status documented after 24th week of pregnancy, if her infant joins Group 5 and is HIV uninfected Parent or guardian of infant intends to remain in the study area for the duration of the trial Inclusion Criteria for HIV Infected Infants: HIV infected Participating in CIPRA SA-Project 2 Exclusion Criteria for All Infants: Blood products prior to study entry Immunosuppressant agents for more than 2 weeks, within 1 week of study entry Unable to tolerate oral medications Presence of any major, life-threatening congenital defect Acute illness or fever requiring hospitalization within 72 hours of immunization Grade 2 vaccine-related allergic reaction Grade 3 or 4 clinical or laboratory toxicity related to vaccination Use of any antiretroviral therapies other than those allowed in CIPRA SA-Project 2. Infants who received antiretroviral drugs used to prevent mother-to-infant HIV transmission are eligible for this study. Use of investigational drugs, systemic cytotoxic chemotherapy, or interleukin or other immune modulators Require certain medications Exclusion Criteria for HIV Uninfected Infants: Vaccines prior to study entry. Infants who have received bacille Calmette-Guerin or oral polio vaccines are not excluded.

Ages Eligible for Study
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Minimum Age: 4 Weeks
Maximum Age: 10 Weeks

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>HIV-uninfected infants born to HIV-uninfected mothers | Biological: Pneumococcal polysaccharide-protein conjugate vaccine<br>* Injection administered three times before the age of 24 weeks<br>* Other names: PncCV;|
| Experimental: 2<br>HIV-infected infants in CDC Disease Category 1 who were randomly assigned to the delayed therapy arm (Arm 1) of CIPRA SA-Project 2 | Biological: Pneumococcal polysaccharide-protein conjugate vaccine<br>* Injection administered three times before the age of 24 weeks<br>* Other names: PncCV;|
| Experimental: 3<br>HIV-infected infants in CDC Disease Category 1 who were randomly assigned to the first early therapy arm (Arm 2) of CIPRA SA-Project 2 | Biological: Pneumococcal polysaccharide-protein conjugate vaccine<br>* Injection administered three times before the age of 24 weeks<br>* Other names: PncCV;|
| Experimental: 4<br>HIV-infected infants in CDC Disease Category 2 or 3 who were randomly assigned to the second early therapy arm (Arm 3) of CIPRA SA-Project 2 | Biological: Pneumococcal polysaccharide-protein conjugate vaccine<br>* Injection administered three times before the age of 24 weeks<br>* Other names: PncCV;|
| Experimental: 5<br>HIV-uninfected infants born to HIV infected mothers | Biological: Pneumococcal polysaccharide-protein conjugate vaccine<br>* Injection administered three times before the age of 24 weeks<br>* Other names: PncCV;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response rate to PncCV among children in Group 2 compared to those in Groups 1 and 3 |  | At Weeks 3 and 6 | 
| Response rate to PncCV among children in Group 2 compared to those in Groups 1 and 3 before receiving booster vaccine dose |  | At Weeks 64 through 76 | 
| Vaccine safety profiles after each of the three primary doses of PncCV and booster doses of PncCV and HibCV |  | Throughout study | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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MTCT