Clinical trial NCT00257127: Immune System Function Following Vaccination in HIV Infected Children Taking Anti-HIV Drugs
Official title: Evaluation of Immunologic Memory Following Pneumococcal, Hepatitis B, and Measles Vaccination in HIV Infected Children Treated With Highly Active Antiretroviral Therapy (HAART)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: HIV Infections
Keywords: Vaccination
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
Collaborators: name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
First posted: 2005-11-22
Enrollment: 101
Sex: ALL
Minimum age (years): 6
Maximum age (years): 23
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine immune system function following vaccination in HIV-infected children currently taking anti-HIV drugs. To test the effectiveness of prior vaccination, patients in this study will receive booster shots of one of two pneumococcal vaccines, a hepatitis B vaccine, and a measles vaccine.

Detailed description: With their immunocompromised status, HIV-infected children are at especially high risk for opportunistic infections, including infection by Streptococcus pneumoniae, hepatitis B, and measles. In PACTG P1024, HIV-infected children taking highly active antiretroviral therapy (HAART) received 2 doses of the pneumococcal conjugate vaccine (PCV), 1 dose of the pneumococcal polysaccharide vaccine (PPV), and booster shots of the hepatitis B vaccine (HBV) and measles, mumps, and rubella vaccine (MMR). Early responses to these vaccinations were favorable, but with declining antibody responses within the 18 months after vaccination. It is unknown if additional booster vaccinations in these children will result in a protective immunologic memory upon re-exposure to these pathogens. This study will determine whether HIV-infected children on HAART have evidence of specific immunologic memory 3 to 4 years after vaccination in PACTG P1024.

Patients will be randomly assigned to receive PCV or PPV at study entry. All eligible patients will also receive HBV and MMR at study entry. Patients will be monitored in the clinic for 1 hour after vaccination for any adverse effects. Study staff will contact patients by phone around Day 3 after study entry to ask patients if they have experienced any adverse effects to the vaccinations; patients who received MMR at study entry will be contacted again around Day 21. Some patients may be asked to return to the clinic for further evaluation if they experience side effects.

There will be study visits at study entry and Days 7 and 28. Medical history, a physical exam, blood collection, and an assessment of HIV-related symptoms will occur at all visits. HAART will not be provided by this study.

Eligibility criteria: Inclusion Criteria:

* Completed the 96-week initial study period of PACTG P1024 and had enrolled into that study between June 1, 2001 and March 31, 2002
* Fulfilled PACTG P1024's definition of HAART (taking 3 or more antiretrovirals \[ARVs\] from at least 2 of the available therapeutic drug classes) during PACTG P1024's vaccination period (Weeks 0 to 24). Patients who were taking 3 nucleoside reverse transcriptase inhibitors during that period without a non-nucleoside reverse transcriptase inhibitor or a protease inhibitor (PI) are not eligible for this study. Nontherapeutic boosting doses of ritonavir used in ritonavir-boosted PI regimens are not counted as separate ARVs.
* Stable ARV regimen in the 4 weeks prior to study entry
* No changes anticipated to current ARV regimen during this study
* Willing to complete all study vaccinations and evaluations
* Willing to use acceptable forms of contraception, if applicable
* Parent or guardian willing to provide informed consent, if applicable

Exclusion Criteria:

* Abnormal blood or chemistry values on most recent laboratory tests. More information on this criterion can be found in the protocol.
* Received PCV, HBV, PPV, or MMR vaccines during PACTG P1024 in a sequence other than specified in PACTG P1024
* Received one or more doses of each of PCV, PPV, MMR, or HBV vaccines since the end of PACTG P1024's vaccination period
* Previous Grade 3 or higher adverse events or allergic reactions judged to be possibly or definitely related to the PCV, PPV, MMR, or HBV vaccines
* Received any killed vaccine within the 4 weeks prior to study entry
* Received any live vaccine within the 6 weeks prior to study entry
* Planning to receive any killed or live vaccine other than study vaccines between the first and third study visits
* Presence of an underlying condition that contraindicates use of any of the study vaccines. Patients who have a CD4% less than 15% will not be given the MMR vaccine, but such patients will not be excluded from this study.
* Current immunomodulatory therapy, including IL-2, any interferon product, GM-CSF, or thalidomide. Patients taking G-CSF or erythropoietin are not excluded.
* Anticipated need for immunomodulatory treatment during this study
* Any intramuscular immune globulin product within the 6 months prior to study entry
* Intravenous immune globulin within the 11 months prior to study entry
* Platelets or plasma products within the 7 months prior to study entry
* Anticipated need for immune globulin products during this study
* Current systemic immunosuppressive therapy, including the equivalent of 1 mg/kg/day or greater of prednisone in the 2 weeks prior to study entry. Patients using inhaled corticosteroids only are not excluded from this study. More information on this criterion can be found in the protocol.
* Anticipated need for systemic immunosuppressive therapy during this study
* Other known or suspected diseases of the immune system
* Cancer in the 3 months prior to study entry or treatment for cancer within the 3 months prior to study entry
* Other acute or chronic medical or surgical conditions or contraindications that, in the opinion of the investigator, may interfere with the study
* Known bleeding disorder
* Any Grade 2 or higher clinical toxicity at study screening. More information on this criterion can be found in the protocol.
* Require certain medications
* Pregnancy

Primary outcomes:
measure: Grade 3 or greater hematologic and chemistry laboratory values, signs, or symptoms not present, as specified by the protocol
timeFrame: At study entry
Secondary outcomes:
measure: Seropositivity, as determined by antibody levels
timeFrame: At study entry and Days 7 and 28
measure: Immunologic memory, as determined by primary and secondary responses, antibody levels, and additional measures of immunologic memory
timeFrame: Throughout study
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: UAB, Dept. of Ped., Div. of Infectious Diseases
state: Alabama
city: Alhambra
country: United States
facility: Usc La Nichd Crs
state: California
city: Long Beach
country: United States
facility: Long Beach Memorial Med. Ctr., Miller Children's Hosp.
state: California
city: San Diego
country: United States
facility: UCSD Mother-Child-Adolescent Program CRS
state: California
city: Aurora
country: United States
facility: Univ. of Colorado Denver NICHD CRS
state: Colorado
city: New Haven
country: United States
facility: Yale Univ. School of Medicine - Dept. of Peds., Div. of Infectious Disease
state: Connecticut
city: Fort Lauderdale
country: United States
facility: South Florida CDTC Ft Lauderdale NICHD CRS
state: Florida
city: Gainesville
country: United States
facility: Univ. of Florida College of Medicine-Dept of Peds, Div. of Immunology, Infectious Diseases & Allergy
state: Florida
city: Jacksonville
country: United States
facility: Univ. of Florida Jacksonville NICHD CRS
state: Florida
city: Chicago
country: United States
facility: Chicago Children's CRS
state: Illinois
city: Chicago
country: United States
facility: Univ. of Chicago - Dept. of Peds., Div. of Infectious Disease
state: Illinois
city: New Orleans
country: United States
facility: Children's Hosp.
state: Louisiana
city: Boston
country: United States
facility: HMS - Children's Hosp. Boston, Div. of Infectious Diseases
state: Massachusetts
city: Boston
country: United States
facility: BMC, Div. of Ped Infectious Diseases
state: Massachusetts
city: Worcester
country: United States
facility: WNE Maternal Pediatric Adolescent AIDS CRS
state: Massachusetts
city: Newark
country: United States
facility: Rutgers - New Jersey Medical School CRS
state: New Jersey
city: Bronx
country: United States
facility: Bronx-Lebanon Hosp. IMPAACT CRS
state: New York
city: Brooklyn
country: United States
facility: SUNY Downstate Med. Ctr., Children's Hosp. at Downstate NICHD CRS
state: New York
city: New York
country: United States
facility: Nyu Ny Nichd Crs
state: New York
city: New York
country: United States
facility: Metropolitan Hosp. Ctr.
state: New York
city: New York
country: United States
facility: Harlem Hosp. Ctr. NY NICHD CRS
state: New York
city: Rochester
country: United States
facility: Strong Memorial Hospital Rochester NY NICHD CRS
state: New York
city: Stony Brook
country: United States
facility: SUNY Stony Brook NICHD CRS
state: New York
city: Philadelphia
country: United States
facility: St. Christopher's Hosp. for Children
state: Pennsylvania
city: San Juan
country: Puerto Rico
facility: Univ. of Puerto Rico Ped. HIV/AIDS Research Program CRS
city: San Juan
country: Puerto Rico
facility: San Juan City Hosp. PR NICHD CRS
Study officials:
affiliation: The Children's Hospital, Denver, CO
name: Mark Abzug, MD
role: STUDY_CHAIR
References:
citation: Obaro SK, Pugatch D, Luzuriaga K. Immunogenicity and efficacy of childhood vaccines in HIV-1-infected children. Lancet Infect Dis. 2004 Aug;4(8):510-8. doi: 10.1016/S1473-3099(04)01106-5.
citation: Abzug MJ, Song LY, Levin MJ, Nachman SA, Borkowsky W, Pelton SI; International Maternal Pediatric Adolescent AIDS Clinical Trials Group P1024 and P1061s Protocol Teams. Antibody persistence and immunologic memory after sequential pneumococcal conjugate and polysaccharide vaccination in HIV-infected children on highly active antiretroviral therapy. Vaccine. 2013 Oct 1;31(42):4782-90. doi: 10.1016/j.vaccine.2013.08.002. Epub 2013 Aug 14.