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

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

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).

Study Overview

• Status: Completed
• Conditions: HIV/AIDS; Streptococcal Pneumonia
• Intervention / Treatment: Biological: Prevenar13

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 70
• Phase: Phase 4

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Korea University Guro Hospital

Study record dates

Study Major Dates

• Study Start (Actual): April 2, 2015
• Primary Completion (Actual): January 31, 2017
• Study Completion (Actual): February 28, 2017

Study Registration Dates

• First Submitted: February 10, 2019
• First Submitted That Met QC Criteria: February 10, 2019
• First Posted (Actual): February 12, 2019

Study Record Updates

• Last Update Posted (Actual): February 12, 2019
• Last Update Submitted That Met QC Criteria: February 10, 2019
• Last Verified: February 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia; Lung Diseases; Bacterial Infections; Bacterial Infections and Mycoses; Streptococcal Infections; Gram-Positive Bacterial Infections; Pneumonia, Bacterial; Pneumococcal Infections; Pneumonia, Pneumococcal; Physiological Effects of Drugs; Immunologic Factors; Heptavalent Pneumococcal Conjugate Vaccine
• Other Study ID Numbers: 2014GR0014

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes