Immunogenicity and Safety of 13-valent Pneumococcal Conjugate Vaccine Among HIV-infected Adults

Study Overview
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Brief Summary
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HIV-infected patients are 30- to 100-fold more susceptible to invasive pneumococcal diseases. Pneumococcal vaccination is the best way to decrease the large pneumococcal disease burden, but the optimal timing of vaccination is still unclear. HIV-infected subjects aged ≥ 18 years were recruited and divided into two age-matched groups: group 1 (subjects with CD4 T-cell counts ≥350 cells/µL) and group 2 (subjects with CD4 T-cell counts <350 cells/µL). Multiplex opsonophagocytic killing assay was used to compare immunogenicity after the immunization of 13-valent pneumococcal conjugate vaccine (PCV13).

Detailed Description
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This single-center, open-label non-randomized clinical trial was conducted at Korea University Guro Hospital from April 2015 to January 2017. Based on the CD4 T-cell counts at the time of study enrollment, HIV-infected subjects aged ≥ 18 years were divided into two groups, group 1 (subjects with CD4 T-cell counts ≥350 cells/µL) and group 2 (subjects with CD4 T-cell counts <350 cells/µL). The primary objective of the study was to demonstrate that the immune responses to PCV13 serotypes in Group 2 (CD4 T-cell counts <350 cells/µL) were not inferior to those in Group 1 (CD4 T-cell counts ≥350 cells/µL) at one month after vaccination. In addition, the safety profiles of PCV13 were compared between two study groups. HIV-infected subjects aged ≥ 18 years with stable underlying diseases (≥ 4 weeks on HAART) were eligible for this study. All available subjects with low CD4 T-cell counts (<350 cells/µL, group 2) were recruited, and age/visit day-matched controls with high CD4 T-cell counts (≥350 cells/µL, group 1) were enrolled. The exclusion criteria were as follows: 1) a history of pneumococcal infection within the recent five years, 2) previous pneumococcal vaccination, 3) current opportunistic infections, 4) known immunodeficiency other than HIV infection and 5) coagulation disorders. The study was approved by the ethics committee of Korea University Guro Hospital (IRB No. 2014GR0014) and was conducted in accordance with the Declaration of Helsinki and Good Clinical Practice. Informed consent was taken for all participants before enrollment. Venous blood samples of 10 mL were collected on day 0 and post-vaccination day 28 ± 7.

Official Title
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Immunogenicity and Safety of 13-valent Pneumococcal Conjugate Vaccine Among HIV-infected Adults in the Era of Highly Active Antiretroviral Therapy: Analysis Stratified by CD4 T-cell Count

Conditions
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Streptococcal Pneumonia, HIV/AIDS

Intervention / Treatment
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* Biological: Prevenar13


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: HIV-infeted subjects who received antiretroviral therapy for ≥ 4 weeks Exclusion Criteria: a history of pneumococcal infection within the recent five years previous pneumococcal vaccination current opportunistic infections known immunodeficiency other than HIV infection coagulation disorders

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: HIV-infected subjects with CD4 T-cell counts <350 cells/µL<br>Intervention to be administered: Prevenar13 | Biological: Prevenar13<br>* Prevenar13 for both arms<br>|
| Active Comparator: HIV-infected subjects with CD4 T-cell counts ≥350 cells/µL<br>Intervention to be administered: Prevenar13 | Biological: Prevenar13<br>* Prevenar13 for both arms<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Opsonophagocytic assay (OPA) titers for PCV13 | OPA geometric mean titers for 13 PCV13 serotypes with corresponding 2-sided 95% confidence intervals between groups receiving PCV 13 and then compare the results | Outcome measure will be assessed at two points (baseline and 28 ± 7 days after vaccination). | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency and duration of local and systemic adverse events | The safety profiles of co-administration of Fluad and PCV13 will be compared to those of single vaccination. | All participants will be followed until 4 weeks after vaccination |