The Effects of Anti-HIV Therapy on the Immune Systems of Children and Young Adults Infected With HIV

Condition(s) targeted: HIV Infections

Intervention: Tetanus toxoid (Biological); Hepatitis A Vaccine (Inactivated) (Biological)

Phase: N/A

Status: Completed

Sponsored by: National Institute of Allergy and Infectious Diseases (NIAID)

Official(s) and/or principal investigator(s):
William Borkowsky, MD, Study Chair, Affiliation: New York University Medical Center
Mona Rigaud, MD, MPH, Study Chair, Affiliation: New York University Medical Center

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.

Official title: The Effects of Highly Active Antiretroviral Therapy (HAART) on the Recovery of Immune Function in HIV-Infected Children and Young Adults

Study design: Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Efficacy Study

Primary outcome:

A stimulation index of 3 or greater on at least 2 occasions to tetanus

positive serologic response to hepatitis A

four-fold increase over baseline in antibody titers for tetanus

Secondary outcome:

A stimulation index of 3 or greater on at least 2 occasions to hepatitis A and Candida

increase in CD4 cell percentage by 10% and absolute CD4 number by 150 cells/ml

development of any adverse events of Grade 3 or higher attributable to vaccination

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.

Minimum age: 2 Years. Maximum age: 24 Years. Gender(s): Both.

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

San Juan City Hosp, San Juan 009367344, Puerto Rico

Univ of Puerto Rico / Univ Children's Hosp AIDS, San Juan 009365067, Puerto Rico

Ramon Ruiz Arnau Univ Hosp / Pediatrics, Bayamon 00956, Puerto Rico

Univ of Alabama at Birmingham - Pediatric, Birmingham, Alabama 35233, United States

Phoenix Childrens Hosp, Phoenix, Arizona 85006, United States

UCSF / Moffitt Hosp - Pediatric, San Francisco, California 941430105, United States

UCSD Med Ctr / Pediatrics / Clinical Sciences, La Jolla, California 920930672, United States

Children's Hosp of Oakland, Oakland, California 946091809, United States

Long Beach Memorial (Pediatric), Long Beach, California 90801, United States

Harbor - UCLA Med Ctr, Torrance, California 90509, United States

Los Angeles County - USC Med Ctr, Los Angeles, California 90033, United States

Children's Hosp of Denver, Denver, Colorado 802181088, United States

Yale Univ Med School, New Haven, Connecticut 06504, United States

Howard Univ Hosp, Washington, District of Columbia 20060, United States

Children's Hosp of Washington DC, Washington, District of Columbia 200102916, United States

Univ of Miami (Pediatric), Miami, Florida 33161, United States

North Broward Hosp District, Fort Lauderdale, Florida 33311, United States

Univ of Florida Gainesville, Gainesville, Florida 32610, United States

Palm Beach County Health Dept, Riviera Beach, Florida 33404, United States

Univ of South Florida, St. Petersburg, Florida 33701, United States

Medical College of Georgia, Augusta, Georgia 30912, United States

Chicago Children's Memorial Hosp, Chicago, Illinois 606143394, United States

The Univ of Chicago Childrens Hosp, Chicago, Illinois 60637, United States

Tulane Univ / Charity Hosp of New Orleans, New Orleans, Louisiana 701122699, United States

Johns Hopkins Hosp - Pediatric, Baltimore, Maryland 212874933, United States

Univ of Maryland (Pediatric), Baltimore, Maryland 21201, United States

Children's Hosp of Boston, Boston, Massachusetts 021155724, United States

Boston City Hosp / Pediatrics, Boston, Massachusetts 02118, United States

Baystate Med Ctr of Springfield, Springfield, Massachusetts 01199, United States

Univ of Massachusetts Med School, Worcester, Massachusetts 016550001, United States

Univ of Mississippi Med Ctr, Jackson, Mississippi 39213, United States

Univ of Medicine & Dentistry of New Jersey / Univ Hosp, Newark, New Jersey 071032714, United States

UMDNJ - Robert Wood Johnson Med School / Pediatrics, New Brunswick, New Jersey 089030019, United States

Harlem Hosp Ctr, New York, New York 10037, United States

North Shore Univ Hosp, Great Neck, New York 11021, United States

Schneider Children's Hosp, New Hyde Park, New York 11040, United States

NYU/Bellevue Hospital, New York, New York 10016, United States

Columbia Presbyterian Med Ctr, New York, New York 10032, United States

SUNY Health Sciences Ctr at Syracuse / Pediatrics, Syracuse, New York 13210, United States

Bronx Lebanon Hosp Ctr, Bronx, New York 10457, United States

Incarnation Children's Ctr / Columbia Presbyterian Med Ctr, New York, New York 10032, United States

State Univ of New York at Stony Brook, Stony Brook, New York 117948111, United States

New York Hosp - Cornell Med Ctr, New York, New York 10021, United States

Univ of Rochester Med Ctr, Rochester, New York 146420001, United States

Montefiore Med - AECOM, Bronx, New York 10461-1046, United States

Mt. Sinai Medical Center, New York, New York 10029, United States

Metropolitan Hospital Center, New York, New York 10029, United States

Duke Univ Med Ctr, Durham, North Carolina 277103499, United States

Childrens Hospital of Philadelphia, Philadelphia, Pennsylvania 19104-4318, United States

Med Univ of South Carolina, Charleston, South Carolina 294253312, United States

Texas Children's Hosp / Baylor Univ, Houston, Texas 77030, United States

Med College of Virginia, Richmond, Virginia 23219, United States

Children's Hospital & Medical Center / Seattle ACTU, Seattle, Washington 981050371, United States

Haga clic aquí para ver información sobre este ensayo clínico en español.

Related publications:

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.

Last updated: October 5, 2007