Pneumococcal Conjugate Vaccination in HIV in Comparison to Polysaccharide Vaccine Boosting

An Open-Label, Phase III, Randomized Study of Pneumococcal Conjugate Vaccination in HIV, in Comparison to Polysaccharide Vaccine Boosting in Previously Vaccinated Patients

Purpose: To study the immune response of the newly licensed pneumococcal conjugate vaccine (PCV) in comparison to the pneumococcal polysaccharide vaccine (PPV) to determine if a significantly better immunologic response to boosting can be elicited in patients previously vaccinated with PPV.

Study Overview

• Status: Completed
• Conditions: HIV Infections; Streptococcus Pneumoniae
• Intervention / Treatment: Biological: pneumococcal conjugate vaccine; Biological: pneumococcal polysaccharide vaccine

• Study Type: Interventional
• Enrollment (Actual): 275
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • California
    • San Diego, California, United States, 92134
      • Naval Medical Center San Diego
  • District of Columbia
    • Washington, District of Columbia, United States, 20307
      • Walter Reed Army Medical Center
  • Hawaii
    • Tripler AMC, Hawaii, United States, 96859
      • Tripler Army Medical Center
  • Maryland
    • Bethesda, Maryland, United States, 20814
      • National Naval Medical Center
  • Texas
    • Lackland Air Force Base, Texas, United States, 78236
      • San Antonio Military Medical Center
  • Virginia
    • Portsmouth, Virginia, United States, 23708
      • Naval Medical Center Portsmouth

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria for HIV positive subjects:

1. At least one prior PPV ≥ 3 and < 8 years ago, while HIV positive. There is no upper limit to the number of previously received PPVs.
2. HIV-positive (except 25 HIV-negative persons as control group).
3. Age between 18 and 60 years of age.
4. Availability of patient to remain within the immediate area for the period of the study and be able to comply with protocol requirements.

Exclusion Criteria for HIV positive subjects:

1. Prior allergic reaction to the PPV
2. Allergic to components of PCV, including diphtheria toxin.
3. Pregnant or lactating females as defined by history or positive HCG urine test.
4. History of chronic viral hepatitis or biochemical evidence to include pretreatment AST or ALT values greater than 3 fold higher than upper limit of normal, or a creatinine of greater than 1.8 mg/dl
5. History of splenectomy
6. Temperature of >38C
7. Inability to ambulate for more than 1000 meters secondary to fatigue, pain or weakness.
8. Patients in whom IM vaccination is not possible because of disease or medication. (e.g. hemophilia, coumadin therapy).
9. Patients diagnosed with HIV wasting disease
10. Viral load over 50,000 copies/ml.
11. History or evidence of recent illicit drug or alcohol abuse.
12. Use of immunosuppressive agents, to include corticosteroids and cancer chemotherapeutic agents.

Inclusion Criteria for HIV negative subjects:

1. HIV-negative by HIV ELISA within the last 12 months
2. Age between 18 and 60 years of age.
3. Availability of patient to remain within the immediate area for the period of the study and be able to comply with protocol requirements.

Exclusion Criteria for HIV negative subjects:

1. Prior PCV and/or PPV vaccination.
2. Prior allergic reaction to the PPV
3. Allergic to components of PCV, including diphtheria toxin.
4. Pregnant or lactating females as defined by history or positive HCG urine test.
5. History of chronic viral hepatitis or biochemical evidence to include pretreatment AST or ALT values greater than 3 fold higher than upper limit of normal, or a creatinine of greater than 1.8 mg/dl
6. History of splenectomy
7. Temperature of >38C
8. Inability to ambulate for more than 1000 meters secondary to fatigue, pain or weakness.
9. Patients in whom IM vaccination is not possible because of disease or medication. (e.g. hemophilia, coumadin therapy).
10. History or evidence of recent illicit drug or alcohol abuse.
11. Use of immunosuppressive agents, to include corticosteroids and cancer chemotherapeutic agents.
12. Works in chain of command of primary/associate investigators.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1; PCV, 210 patients	Biological: pneumococcal conjugate vaccine; Prevnar is manufactured as a liquid preparation. Each 0.5 mL dose is formulated to contain: 2 μg of each saccharide for serotypes 4, 9V, 14, 18C, 19F, and 23F, and 4 μg of serotype 6B per dose (16 μg total saccharide); approximately 20 μg of CRM197 carrier protein; and 0.125 mg of aluminum per 0.5 mL dose as aluminum phosphate adjuvant. After shaking, the vaccine is a homogeneous, white suspension.; Other Names: PCV
Active Comparator: Group 2; PPV, 110 patients	Biological: pneumococcal polysaccharide vaccine; PNEUMOVAX 23 is manufactured according to methods developed by the Merck Research Laboratories. Each 0.5 mL dose of vaccine contains 25 μg of each polysaccharide type in isotonic saline solution containing 0.25% phenol as a preservative.; Other Names: PPV
Active Comparator: Group 3; PCV, HIV-negative, 25 patients	Biological: pneumococcal conjugate vaccine; Prevnar is manufactured as a liquid preparation. Each 0.5 mL dose is formulated to contain: 2 μg of each saccharide for serotypes 4, 9V, 14, 18C, 19F, and 23F, and 4 μg of serotype 6B per dose (16 μg total saccharide); approximately 20 μg of CRM197 carrier protein; and 0.125 mg of aluminum per 0.5 mL dose as aluminum phosphate adjuvant. After shaking, the vaccine is a homogeneous, white suspension.; Other Names: PCV

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Positive Immune Responses in the Human Immunodeficiency Virus (HIV)-Infected Pneumococcal Conjugate Vaccine (PCV) and Pneumococcal Polysaccharide Vaccine (PPV) Arms	The primary end point is greater than or equal to a 2-fold increase in the IgG level for at least 2 of the 4 serotypes on day 60, with levels greater than or equal to 1000 ng/mL.	Day 14, 60, and 180 after vaccination
Adverse Events (AEs) Occurring Temporally (Within 7 Days) in Association With Pneumococcal Vaccination		Day 7 after vaccination

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assessment of CD4+ Cell Count Changes Caused by Vaccination With PCV and PPV.	The pairwise change in CD4+ cell count from the time of screening to each time frame (day 14, day 60 and day 180 post-vaccination) (CD4+ cell count at day 14/60/180 [minus] CD4+ cell count at screening). Analysis Population Description (further details): not all participants completed each follow-up visit. Therefore, a different number of participants analyzed is noted for each visit day. For example, in Group 1, 131 participants completed the screening visit but only 129 completed Day 14, and only 123 completed Day 60, etc.	Day 14, 60, and 180 after vaccination
Assessment of the Importance of the Host Immune Status (CD4+ Count) on the PCV and PPV Immunologic Response.	Number with ≥ Successes, which is defined as: Success = 2-fold increase on Log10 scale -- if log10(Day 60) - log10(Screening) > log10(2)	Day 60 after vaccination
Assessment of Viral Load Changes Caused by Vaccination With PCV and PPV.	The pairwise change in viral load from the time of screening to each time frame (day 14, day 60 and day 180 post-vaccination), similar to CD4 change above.	Day 14, 60, and 180 after vaccination

Collaborators and Investigators

• Sponsor: Henry M. Jackson Foundation for the Advancement of Military Medicine
• Collaborators: National Institute of Allergy and Infectious Diseases (NIAID); Uniformed Services University of the Health Sciences; US Military HIV Research Program; Infectious Diseases Clinical Research Program
• Investigators: Principal Investigator: Brian Agan, MD, Uniformed Services University of the Health Sciences

Publications and helpful links

General Publications

• Crum-Cianflone NF, Roediger M, Huppler Hullsiek K, Ganesan A, Landrum M, Weintrob A, Agan B, Medina S, Rahkola J, Hale B, Janoff EN; Infectious Disease Clinical Research Program HIV Working Group. The association of ethnicity with antibody responses to pneumococcal vaccination among adults with HIV infection. Vaccine. 2010 Nov 10;28(48):7583-8. doi: 10.1016/j.vaccine.2010.09.056. Epub 2010 Sep 29.
• Crum-Cianflone NF, Huppler Hullsiek K, Roediger M, Ganesan A, Patel S, Landrum ML, Weintrob A, Agan BK, Medina S, Rahkola J, Hale BR, Janoff EN; Infectious Disease Clinical Research Program HIV Working Group. A randomized clinical trial comparing revaccination with pneumococcal conjugate vaccine to polysaccharide vaccine among HIV-infected adults. J Infect Dis. 2010 Oct 1;202(7):1114-25. doi: 10.1086/656147.

Study record dates

Study Major Dates

• Study Start: December 1, 2002
• Primary Completion (Actual): July 1, 2013
• Study Completion (Actual): July 1, 2013

Study Registration Dates

• First Submitted: February 13, 2008
• First Submitted That Met QC Criteria: February 22, 2008
• First Posted (Estimated): February 25, 2008

Study Record Updates

• Last Update Posted (Actual): June 8, 2025
• Last Update Submitted That Met QC Criteria: May 21, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Keywords: HIV; Streptococcus pneumoniae; Prevnar; Pneumovax; PCV; pneumococcal conjugate vaccine; PPV; polysaccharide vaccine
• Additional Relevant MeSH Terms: Respiratory Tract Infections; Infections; Respiratory Tract Diseases; Lung Diseases; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Streptococcal Infections; Pneumococcal Infections; Pneumonia, Bacterial; Pneumonia; Pneumonia, Pneumococcal; Immunologic Factors; Physiological Effects of Drugs; Heptavalent Pneumococcal Conjugate Vaccine; Vaccines
• Other Study ID Numbers: RV150 Prevnar