Clinical trial NCT00004735: The Effects of Anti-HIV Therapy on the Immune Systems of Children and Young Adults Infected With HIV
Official title: The Effects of Highly Active Antiretroviral Therapy (HAART) on the Recovery of Immune Function in HIV-Infected Children and Young Adults
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: HIV Infections
Keywords: Viral Vaccines
Drug Therapy, Combination
CD4-Positive T-Lymphocytes
Immunologic Memory
Antibody Formation
Anti-HIV Agents
Tetanus Toxoid
Hepatitis A Virus, Human
Enfuvirtide
T-20
Treatment Naive
Treatment Experienced
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: 81
Sex: ALL
Minimum age (years): 2
Maximum age (years): 24
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 the number of newly formed CD4 cells in children who have taken anti-HIV drugs. The study will also evaluate the effectiveness of the new CD4 cells in producing an immune response to hepatitis A and tetanus toxoid vaccination.

Study hypothesis: 1) Immunologic reconstitution of individuals who have less than 15% CD4 cells may or may not be associated with functional activity. 2) The functional immunologic responses to recall and newly experienced antigens may be different. 3) The functional responses to antigens delivered in vaccine format may be a function of CD4 level, viral load, or both.

Detailed description: HIV damages the immune system by infecting CD4 cells, white blood cells that help fight infections and protect the body from disease. As CD4 cells die, the immune system becomes weak. Taking anti-HIV drugs slows the ability of the virus to multiply and kill CD4 cells. HIV infected children taking anti-HIV drugs have significant inhibition of HIV growth and significant increases in CD4 cell counts. It is not known to what extent CD4 count increases in HIV infected children translate to functional immune recovery. HIV infected children have typically demonstrated poor serological responses to routine childhood immunizations.

Participants will either begin HAART or make a change to their current HAART regimens at study entry or within 2 weeks prior to study entry. All participants will have viral load testing when they begin or change their HAART regimens. Participants will then have a second viral load test after 4 weeks. Only participants with an acceptable decrease in viral load will continue in the study.

Participants will be randomly assigned to one of two groups. Participants in Group 1 will receive tetanus toxoid immunizations (known as DTaP, DT-pediatric, or Td) at Weeks 8, 16, and 24 and hepatitis A vaccinations at Weeks 32, 40, and 48. Participants in Group 2 will receive hepatitis A vaccinations at Weeks 8, 16, and 24 and tetanus toxoid immunizations at Weeks 32, 40, and 48. Participants will have a physical exam and blood tests at study entry and at Weeks 4, 8, 12, 16, 24, 28, 32, 36, 40, 48, 52, 76, and 100.

As of May 2005, participants will have the option to receive an additional hepatitis A vaccination booster. Those who consent and have not reached Week 100 of the study will receive a booster vaccination at Week 100, with a final follow-up visit occuring at Week 104. Those participants who do not consent will not receive the hepatitis A vaccination booster and will have their last follow-up visit at Week 100.

Eligibility criteria: Inclusion Criteria

* HIV infected
* CD4 percentage less than 15%
* Beginning an anti-HIV drug regimen (HAART) that includes at least 3 drugs. Two of the drugs must be new to the patient. One of the new drugs must be a protease inhibitor or a nonnucleoside reverse transcriptase inhibitor (NNRTI). As of May 2005, patients who have previously taken NNRTIs will have the option of taking Fuzeon as an alternative component of their HAART regimen
* Consent of parent or legal guardian
* As of May 2005, females who become pregnant during the study can continue to participate as long as they become pregnant after receiving all vaccinations

Exclusion Criteria

* Active opportunistic (AIDS-related) or bacterial infection
* Cancer
* Immunity to hepatitis A
* Severe drug toxicity
* Previous severe or allergic reaction to tetanus vaccine
* Taking IVIG, IL-2, or other drugs which affect the immune system
* Taking hydroxyurea
* Pregnancy at screening visit
* Pregnancy before all vaccinations have been administered

Primary outcomes:
measure: A stimulation index of 3 or greater on at least 2 occasions to tetanus
measure: positive serologic response to hepatitis A
measure: four-fold increase over baseline in antibody titers for tetanus
Secondary outcomes:
measure: A stimulation index of 3 or greater on at least 2 occasions to hepatitis A and Candida
measure: increase in CD4 cell percentage by 10% and absolute CD4 number by 150 cells/ml
measure: development of any adverse events of Grade 3 or higher attributable to vaccination
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 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: Washington
country: United States
facility: Children's National Med. Ctr., ACTU
state: District of Columbia
city: Washington
country: United States
facility: Howard Univ. 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: Miami
country: United States
facility: Univ. of Miami Ped. Perinatal HIV/AIDS CRS
state: Florida
city: Tampa
country: United States
facility: USF - Tampa NICHD CRS
state: Florida
city: Chicago
country: United States
facility: Chicago Children's CRS
state: Illinois
city: New Orleans
country: United States
facility: Tulane/LSU Maternal/Child CRS
state: Louisiana
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: Worcester
country: United States
facility: WNE Maternal Pediatric Adolescent AIDS CRS
state: Massachusetts
city: Bronx
country: United States
facility: Bronx-Lebanon Hosp. IMPAACT 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: 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: Seattle
country: United States
facility: UW School of Medicine - CHRMC
state: Washington
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:
affiliation: NYU Langone Health
name: William Borkowsky, MD
role: STUDY_CHAIR
affiliation: NYU Langone Health
name: Mona Rigaud, MD, MPH
role: STUDY_CHAIR
References:
citation: Melvin AJ, Mohan KM. Response to immunization with measles, tetanus, and Haemophilus influenzae type b vaccines in children who have human immunodeficiency virus type 1 infection and are treated with highly active antiretroviral therapy. Pediatrics. 2003 Jun;111(6 Pt 1):e641-4. doi: 10.1542/peds.111.6.e641.
citation: Rigaud M, Borkowsky W, Muresan P, Weinberg A, Larussa P, Fenton T, Read JS, Jean-Philippe P, Fergusson E, Zimmer B, Smith D, Kraimer J; Pediatrics AIDS Clinical Trials Group P1006 Team. Impaired immunity to recall antigens and neoantigens in severely immunocompromised children and adolescents during the first year of effective highly active antiretroviral therapy. J Infect Dis. 2008 Oct 15;198(8):1123-30. doi: 10.1086/592050.