CLEAC (Comparison of Late Versus Early Antiretroviral Therapy in HIV-infected Children)

Study Overview
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Brief Summary
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The study aims to define and compare the immunological characteristics (lymphocyte subpopulations, specific immunity against HIV, lymphocyte activation, inflammatory parameters) and the virological characteristics (study of viral reservoir) between 2 groups of vertically-HIV-1-infected children, between 5 and 17-year-of-age, who started cART before 6 months-of-age (early treatment group) or after 24 months-of-age (late treatment group) with an initial virologic success (HIV-1 RNA <400 copies / mL reached no later than 24 months after the start of cART), whatever the later evolution of the viremia. Moreover, the viral reservoir will be deeply characterized in 10 children (5 patients in each group) with sustained control of the HIV-1 viremia under cART (≥ 90% of HIV-1 RNA measures <400 copies /mL): quantification of the reservoir in the lymphocyte subpopulations and study of the inductibility of the viral reservoir.

Detailed Description
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This is a cross-sectional study, multicenter, without direct benefit, among vertically HIV-1 infected children, aged 5 to 17 years, followed in centers participating in the ANRS CO10 EPF cohort located in Ile-de-France. Eligible children are not necessarily included in the cohort. The sample will consist of two age groups of equal size (5-12 years and 13-17 years). Patient recruitment will be conducted in the centers of the ANRS CO10 EPF cohort located in Ile de France (Paris area). 80 children will be included, previously included or not in the ANRS CO10 EPF cohort. Our investigations will involve two blood samples, taken during two successive visits of the children in the hospitals where they are usually followed. Finally, a third blood sample will be taken during a third visit only for the 10 children participating in the substudy of the viral reservoir. All medical data since birth will be prospectively collected for children included in the ANRS CO10 EPF cohort, and retrospectively collected in the other cases.

Official Title
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ANRS EP59 CLEAC : Physiopathological Study of Immunovirological Evolution of Perinatally HIV-1 Infected Children Depending on Early (Before 6 Months) or Late (After 2 Years) Antiretroviral Therapy Introduction.

Conditions
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HIV Infection

Intervention / Treatment
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* Other: Blood draw


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 5 to 17 years old Vertically HIV-1 infected, not HIV-2 co-infected Diagnosed < 13 years old Usually followed in a center participating in the ANRS CO10 EPF cohort located in Ile de France Have received cART treatment: started later than 6 months-of-age (early treatment group) or after 24 months-of-age (late treatment group) with an initial virologic success (HIV-1 RNA <400 copies / mL reached no later than 24 months after the start of cART), Affiliated person or beneficiary of a social security system (Article L1121-11 of the Code of Public Health) (medical aid of state or AME is not a social security system) Participant agreement if in age to give an opinion Free, informed and written consent, signed by at least one parent and the investigator Exclusion Criteria: < 5 years old or ≥ 18 years old at first sample for the study Obviously HIV-1 infected after the perinatal period HIV-2 co-infected Diagnosed ≥ 13 years old Started cART treatment between 7 and 23 months No HIV-1 RNA <400 copies / mL within 24 months after initiation of treatment (considered as a failure of the first line therapy) Not affiliated to the French social security, or beneficiary of a social security system Refusal to participation of parent(s) (or the holders(s) of parental authority) Refusal to participation if in age to give an opinion.

Ages Eligible for Study
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Minimum Age: 5 Years
Maximum Age: 18 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: Basic Science
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Early treatment group<br>Vertically-HIV-1-infected children, between 5 and 17-year-of-age, who started cART before 6 months-of-age (early treatment group) with an initial virologic success (HIV-1 RNA <400 copies / mL reached no later than 24 months after the start of cART), whatever the later evolution of the viremia. | Other: Blood draw<br> <br> |
| Other: Late treatment group<br>Vertically-HIV-1-infected children, between 5 and 17-year-of-age, who started cART after 24 months-of-age (late treatment group) with an initial virologic success (HIV-1 RNA <400 copies / mL reached no later than 24 months after the start of cART), whatever the later evolution of the viremia. | Other: Blood draw<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Immune status | The immune status will be defined by T lymphocyte subpopulations | Baseline | 
| Virological status | Peripheral blood HIV DNA levels | Baseline | 
| Immune status | The immune status will be defined by inflammatory parameters : cytokines and chemokines | 6 months after baseline | 
| Immune status | The immune status will be defined by HIV-specific T cell response | Baseline | 
| Immune status | The immune status will be defined by lymphocyte activation (HLA-DR) | Baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparison of immune and virological statuses of early and late treatment groups | Two groups of vertically-HIV-1-infected children, between 5 and 18-year-of-age, will be compared: the early treatment group that comprises children who started HAART before 6 months-of-age, and the late treatment group those who started HAART after 24 months-of-age. | Baseline | 
| Viral reservoir : lymphocyte subpopulation | Total HIV- DNA will be quantified by ultrasensitive PCR in CD4 T cell subsets sorted according their differenciation status for 10 children (5 patients in each group) with sustained control of the HIV-1 viremia under HAART ( ≥ 90% of HIV-1 RNA measures <400 copies / ml). | One year after baseline | 
| Viral reservoir : inductibility | Inductibility of the viral reservoir will be quantified by ultrasensitive HIV-RNA RT- PCR in supernatants after coculture of CD4 T cells. | One year after baseline |