Early Anti-Retroviral Treatment in HIV- Infected Children

Study Overview
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Brief Summary
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EARTH study is conducted as part of the EPIICAL project. It is a prospective cohort study which aims to monitor clinical, virological and immunological features of HIV-positive, early treated children (≤90 days after diagnosis), in order to identify participants with excellent viral and immunological control, and also other without excellent control, in order to stratify potential participants in proof-of-concept trials directed to HIV cure.

Detailed Description
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The duration of the study is 4 years from the start of enrollment with at least 4 years of follow-up for each participant. The study is conducted in South Africa, Mali, and Mozambique with an expected enrollment target of 200 participants (as a minimum). In this study, newly diagnosed HIV-infected children will start ART as early as possible, following local standards of care, and will be followed up to 4 years of age. Clinical and blood data for viral load, immunology, and serology will be collected at the 11 visits. HIV reservoir size and HIV-specific immune responses will be analyzed at visit 1 and at 1, 2, 3, and 4 years after enrollment. We will identify children with HIV infection eligible to participate in proof-of-concept treatment/remission studies. A predictive model developed from European participant data will help identify children with low reservoir. These predictions will then be compared with available data from participants already enrolled with an excellent control to refine the model.

Official Title
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A Prospective, Observational, Cohort, Multicenter Study of Early Anti-Retroviral Treatment in HIV- Infected Infants

Conditions
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HIV Infections

Intervention / Treatment
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* Procedure: Blood samples collection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Perinatally infected infants who start ART at ≤90 days after diagnosis (HIV infection diagnosed and confirmed by molecular methods in 2 different samples, i.e., positive qualitative HIV DNA/RNA test). Breastfed-infected children found to be infected ≤ 90 days of age and who started ART at < 90 days after diagnosis. This group will be younger than six months of age at ART initiation. Caregivers (mother, if alive and available) able to provide informed consent. Able to take ART. Exclusion Criteria: Second and successive RNA PCR negative Malignancy Current concomitant immunosuppressive therapy (including>15 days and >2 mg/kg/day of prednisone-equivalent). Caregivers withdraw consent Age >180 days.

Ages Eligible for Study
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Minimum Age: 0 Days
Maximum Age: 180 Days

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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Infants infected through breast-feeding and perinatally<br>Infants infected through breast-feeding and perinatally diagnosed with HIV ≤90 days of age and starting ART ≤90 days after diagnosis. For these patients clinical data and blood for viral load, immunology and serology will be collected in the 11 visits. | Procedure: Blood samples collection<br>* The study population will take blood samples for virological and immunological measurements.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of children with excellent HIV control | Proportion of children with excellent HIV control profile at 2 and 4 years of age. This excellent control profile includes a composite endpoint of all of the following: Undetectable HIV RNA viral load in peripheral blood in the last year (blips, spikes and suboptimal viral control allowed, see below for definitions), Reservoir size (Total DNA /million PBMC) below 25th percentile with ddPCR / IPDA. Good immunological control (defined as a CD4 >30% and a good NK or CTL response) during the last year | 4 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV, Infection, Infants, Antiretroviral Therapy