Treatment With Combinations of Several Antiviral Drugs in Infants and Young Children With HIV Infection

Study Overview
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Brief Summary
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This trial tests the safety and effectiveness of the early use of combinations of anti-HIV drugs in HIV-infected infants and young children in an effort to block virus growth and preserve normal immune functions. Various anti-HIV drug combinations need to be tested in order to find the best way to treat infants and children who have been infected with HIV during birth.

Detailed Description
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This study examines the antiretroviral activity of ZDV/3TC/NVP in vertically-infected infants and children aged 15 days up to 2 years, and ZDV/3TC/NVP/ABC in vertically-infected infants and children aged 30 days up to 2 years. This study will assess HIV-1 and CD4/CD8 T-cell kinetics, activation, and maturation. It will also test the concept that early (younger than 3 months of age) use of potent, combination antiretroviral therapy will allow the long-term control of viral replication with preservation of normal immune function. [AS PER AMENDMENT 3/11/98: This study will also examine the antiretroviral activity of ZDV/3TC/NVP/NFV in vertically infected infants and children.] This is a 2-part Phase I/II, open-label trial in HIV-infected infants. Part A assesses the triple combination of ZDV, 3TC, and NVP. Four to eight patients are enrolled in each age cohort (Cohort 1: at least 15 days, no more than 3 months; Cohort 2: over 3 months, no more than 2 years). Part B assesses the quadruple combination of ZDV, 3TC, NVP, and ABC. Eight patients are enrolled in each age cohort (Cohort 3: at least 30 days, no more than 3 months; Cohort 4: over 3 months, no more than 2 years). [AS PER AMENDMENT 3/11/98: This study is now a 3-part Phase I/II trial. Parts A and B are as above. Part C will assess the quadruple regimen of d4T, 3TC, NVP and NFV. Up to 8 patients will be enrolled in each age cohort (Cohort 5: at least 15 days, no more than 3 months; Cohort 6: over 3 months, no more than 2 years). If 3 of 4 patients in either cohort of Part B do not achieve plasma RNA less than 1,000 copies/ml after 16 weeks of quadruple therapy, enrollment of patients to that cohort will stop and enrollment of 8 patients to the corresponding cohort in Part C will begin. For Part C, patients whose RNA level is no more than 1,000 copies/ml at Week 16 will remain on assigned treatment until Week 104. If at any time between Weeks 16 and 104 a patient's RNA level increases to greater than 1,000 copies/ml, plasma RNA will be repeated within 1 week. If both RNA levels are greater than 1,000 copies/ml, the patient will discontinue study treatment and be followed every 12 weeks for 1 year.] [AS PER AMENDMENT 4/14/99: The study has been extended for an additional 96 weeks for children with continued suppression of viral replication (RNA less than 400 copies/ml) at Week 104. If at any time between Week 12 or 16 and Week 200 a patient's RNA level increases to greater than 1,000 copies/ml, plasma RNA will be repeated within 1 week. If both RNA levels are above 1,000 copies/ml, the patient will discontinue treatment for best available therapy and be followed every 12 weeks for 1 year following the discontinuation of study treatment.] [AS PER AMENDMENT 9/16/99: An additional cohort (Cohort 7) of 5 to 10 patients has been added. Cohort 7 includes patients between 15 days and 3 months of age. Cohort 7 patients who experience suppression of viral replication at Week 104 are followed through Week 200.]

Official Title
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Early Intensive Antiretroviral Combination Therapy in HIV-1 Infected Infants and Children

Conditions
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HIV Infections

Intervention / Treatment
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* Drug: Abacavir sulfate
* Drug: Nelfinavir mesylate
* Drug: Nevirapine
* Drug: Lamivudine
* Drug: Stavudine
* Drug: Zidovudine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Children may be eligible for this study if they: Are 15 days to 2 years old. Have consent of parent or legal guardian. Are HIV-positive. Exclusion Criteria Children will not be eligible for this study if they: Have certain infections which require treatment during the study. Have received certain medications.

Ages Eligible for Study
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Minimum Age: 15 Days
Maximum Age: 2 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: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Abacavir sulfate|nan|
|Drug: Nelfinavir mesylate|nan|
|Drug: Nevirapine|nan|
|Drug: Lamivudine|nan|
|Drug: Stavudine|nan|
|Drug: Zidovudine|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Antiretroviral activity of ZDV/3TC/NVP |  | Throughout study | 
| Durability of viral suppression |  | Throughout study | 
| Immune competence and HIV-1 specific immune respones with prolonged viral suppression beyond 104 weeks |  | Throughout study | 
| Antiretroviral activity of ZDV/3TC/NVP/1592U89 regimen |  | Throughout study | 
| Antiretroviral activity of d4T/3TC/NVP/NFV regimen |  | Throughout study | 
| Tolerance and pharmacokinetic profile of NFV |  | Throughout study | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Virus Replication, HIV-1, Drug Therapy, Combination, Zidovudine, Nevirapine, Stavudine, HIV Protease Inhibitors, CD4 Lymphocyte Count, Lamivudine, RNA, Viral, Reverse Transcriptase Inhibitors, Anti-HIV Agents, Viral Load, Nelfinavir