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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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HIV Infections

Intervention / Treatment
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* Biological: Tetanus toxoid
* Biological: Hepatitis A Vaccine (Inactivated)


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 24 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: Tetanus toxoid|nan|
|Biological: Hepatitis A Vaccine (Inactivated)|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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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