Clinical trial NCT00013871: Pneumococcal Vaccine and Routine Pediatric Immunizations in HIV-Infected Children Receiving Anti-HIV Drugs
Official title: Evaluation of the Immunogenicity of Pneumococcal Conjugate Vaccine and Routine Pediatric Immunizations in HIV-Infected Children Treated With Highly Active Antiretroviral Therapy (HAART)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: HIV Infections
Hepatitis B
Measles
Pneumococcal Infections
Pertussis
Keywords: Measles-Mumps-Rubella Vaccine
Antibodies, Viral
Hepatitis B Vaccines
Immunization, Secondary
Pneumococcal Vaccines
Antiretroviral Therapy, Highly Active
Diphtheria-Tetanus-acellular Pertussis Vaccines
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: 2001-08-31
Enrollment: 300
Sex: ALL
Minimum age (years): 2
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Primary purpose: PREVENTION

Brief summary: The purpose of this study is to determine if 2 doses of Pneumococcal Conjugate Vaccine (PCV) followed by 1 dose of Pneumococcal Polysaccharide Vaccine (PPV) in HIV-infected children on anti-HIV therapy is helpful and safe in fighting pneumococcal infections in this group of children. This study will also look at the protection provided by childhood vaccination against measles, pertussis, and hepatitis B virus.

Pneumococcal infections are the most common AIDS-related infection in HIV-infected children. PCV may help reduce the chances of HIV-infected children getting pneumococcal infections. This study will look at whether pneumococcal vaccines are safe and effective in HIV-infected children receiving HAART. It will look at whether HIV-infected children are protected by childhood vaccines received previously and if more doses are safe and improve protection.

Detailed description: Infection by Streptococcus pneumoniae is the most frequent opportunistic infection observed in HIV-infected children. PCVs are immunogenic and efficacious in normal children and offer hope of reducing pneumococcal infections in HIV-infected children. The degree to which children on HAART are protected by prior immunizations and are responsive to new immunizations is still largely undefined. This study is designed to answer whether PCV immunizations are safe and effective. The immune responses to prior immunizations and responsiveness to booster doses of vaccines against measles, pertussis, and hepatitis B virus of children on HAART will also be examined. Answers to these questions will determine whether these children are likely to be protected against these clinically relevant pathogens and whether they should routinely receive booster doses of these vaccines after a period of HAART.

Patients are stratified on the basis of CD4 percentage and age. Patients that previously received a primary hepatitis B vaccine (HBV) series receive an HBV immunization at entry. Other vaccinations may be given (based on age and/or CD4 cell measurement, and immunization status) for PCV at entry and 2 months, and measles-mumps-rubella (MMR) vaccine and PPV at 4 months. Some patients may be administered DTaP at a 6-month visit on the basis of age, previous immunization history, and negative tetanus antibody status. Follow-up visits are done at 8, 12, and 24 months. Blood samples are collected at all clinic visits for assessment of HIV RNA, immune responses against pneumococcus, measles, pertussis, and hepatitis B virus, as well as for laboratory evaluations.

Eligibility criteria: Inclusion Criteria

Patients may be eligible for this study if they:

* Are 2 to 18 years of age.
* Are HIV-infected.
* Have a viral load (amount of HIV in the blood) under 60,000 copies/ml within 30 days of study entry.
* Have been on their current anti-HIV drugs for at least 3 months.
* Have received 4 or more doses of a pertussis vaccine.
* Have received 1 or more doses of measles vaccine unless a CD4 percent or CD4 number ruled out taking the vaccine. (This reflects a change in the CD4 requirement.)
* Expect to be able to complete all study injections and follow-up.
* Have a negative pregnancy test if able to have children and use effective methods of birth control.
* Have parent or guardian's consent if under 18 years of age.
* Have received an approved hepatitis B vaccine series. Not required for study entry, but children who have received this vaccine will be studied.
* (This study was changed to allow patients who became HIV infected after birth, have a viral load between 30,000 and 60,000 copies/ml, and who have been on their current anti-HIV drugs for 3 to 6 months.)

Exclusion Criteria

Patients will not be eligible for this study if they:

* Had a certain CD4 level before beginning anti-HIV drugs and at screening.
* Have received any killed vaccine within 4 weeks, or any live vaccine within 6 weeks, of entering the study.
* Have received pneumococcal vaccines or had a reaction to PPV.
* Have had an allergic reaction to any measles or hepatitis B vaccines, or to other routine childhood immunizations if 13 years of age or less.
* Have any other condition that would make receiving study vaccines inadvisable.
* Are currently on medications that affect the immune system, except for G-CSF and erythropoietin. This includes the equivalent to more than 1 mg/kg/day of prednisone in the 2 weeks preceding study screening. Nonsteroidal anti-inflammatory agents and inhaled corticosteroids are not excluded.
* Have received certain blood products within the previous 6 months.
* Have other diseases of the immune system.
* Have had cancer within 3 months of study screening or are being treated or have been treated for cancer within 3 months of study entry.
* Are pregnant.
* Have any other disease or previous surgery that would interfere with study treatment.
* Are likely to have bleeding disorders.
* Show certain side effects to vaccines at screening.

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: UAB, Dept. of Ped., Div. of Infectious Diseases
state: Alabama
city: Long Beach
country: United States
facility: Long Beach Memorial Med. Ctr., Miller Children's Hosp.
state: California
city: Los Angeles
country: United States
facility: Usc La Nichd Crs
state: California
city: Oakland
country: United States
facility: Children's Hosp. & Research Ctr. Oakland, Ped. Clinical Research Ctr. & Research Lab.
state: California
city: San Diego
country: United States
facility: UCSD Mother-Child-Adolescent Program CRS
state: California
city: San Francisco
country: United States
facility: UCSF Pediatric AIDS CRS
state: California
city: Aurora
country: United States
facility: Univ. of Colorado Denver NICHD CRS
state: Colorado
city: Hartford
country: United States
facility: Connecticut Children's Med. Ctr.
state: Connecticut
city: New Haven
country: United States
facility: Yale Univ. School of Medicine - Dept. of Peds., Div. of Infectious Disease
state: Connecticut
city: Washington
country: United States
facility: Children's National Med. Ctr. Washington DC NICHD CRS
state: District of Columbia
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: Miami
country: United States
facility: Univ. of Miami Ped. Perinatal HIV/AIDS CRS
state: Florida
city: Columbus
country: United States
facility: Columbus Regional HealthCare System, The Med. Ctr.
state: Georgia
city: Chicago
country: United States
facility: Univ. of Chicago - Dept. of Peds., Div. of Infectious Disease
state: Illinois
city: Chicago
country: United States
facility: Chicago Children's CRS
state: Illinois
city: Baltimore
country: United States
facility: Univ. of Maryland Med. Ctr., Div. of Ped. Immunology & Rheumatology
state: Maryland
city: Baltimore
country: United States
facility: Johns Hopkins Hosp. & Health System - Dept. of Peds., Div. of Infectious Diseases
state: Maryland
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: Springfield
country: United States
facility: Baystate Health, Baystate Med. Ctr.
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: Bronx
country: United States
facility: Montefiore Med. Ctr. - AECOM
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 Hyde Park
country: United States
facility: Schneider Children's Hosp., Div. of Infectious Diseases
state: New York
city: New York
country: United States
facility: Nyu Ny Nichd Crs
state: New York
city: New York
country: United States
facility: Columbia IMPAACT CRS
state: New York
city: New York
country: United States
facility: Harlem Hosp. Ctr. NY NICHD CRS
state: New York
city: New York
country: United States
facility: Cornell Univ., Div. of Ped. Infectious Diseases & Immunology
state: New York
city: New York
country: United States
facility: Metropolitan Hosp. Ctr.
state: New York
city: New York
country: United States
facility: St. Luke's-Roosevelt Hosp. Ctr.
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: Houston
country: United States
facility: Texas Children's Hosp. CRS
state: Texas
city: San Juan
country: Puerto Rico
facility: San Juan City Hosp. PR NICHD CRS
city: San Juan
country: Puerto Rico
facility: Univ. of Puerto Rico Ped. HIV/AIDS Research Program CRS
Study officials:
name: Mark Abzug
role: STUDY_CHAIR
References:
citation: Abzug MJ, Qin M, Levin MJ, Fenton T, Beeler JA, Bellini WJ, Audet S, Sowers SB, Borkowsky W, Nachman SA, Pelton SI, Rosenblatt HM; International Maternal Pediatric Adolescent AIDS Clinical Trials Group P1024 and P1061s Protocol Teams. Immunogenicity, immunologic memory, and safety following measles revaccination in HIV-infected children receiving highly active antiretroviral therapy. J Infect Dis. 2012 Aug 15;206(4):512-22. doi: 10.1093/infdis/jis386. Epub 2012 Jun 12.
citation: Abzug MJ, Warshaw M, Rosenblatt HM, Levin MJ, Nachman SA, Pelton SI, Borkowsky W, Fenton T; International Maternal Pediatric Adolescent AIDS Clinical Trials Group P1024 and P1061s Protocol Teams. Immunogenicity and immunologic memory after hepatitis B virus booster vaccination in HIV-infected children receiving highly active antiretroviral therapy. J Infect Dis. 2009 Sep 15;200(6):935-46. doi: 10.1086/605448.
citation: Abzug MJ, Song LY, Fenton T, Nachman SA, Levin MJ, Rosenblatt HM, Pelton SI, Borkowsky W, Edwards KM, Peters J; International Maternal Pediatric Adolescent AIDS Clinical Trials Group P1024 Protocol Team. Pertussis booster vaccination in HIV-infected children receiving highly active antiretroviral therapy. Pediatrics. 2007 Nov;120(5):e1190-202. doi: 10.1542/peds.2007-0729. Epub 2007 Oct 15.