Clinical trial NCT02674867: CLEAC (Comparison of Late Versus Early Antiretroviral Therapy in HIV-infected Children)
Official title: 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.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: HIV Infection
Lead sponsor: ANRS, Emerging Infectious Diseases
Sponsor class: OTHER_GOV
First posted: 2016-02-05
Enrollment: 80
Sex: ALL
Minimum age (years): 5
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Immune status
timeFrame: Baseline
measure: Virological status
timeFrame: Baseline
measure: Immune status
timeFrame: 6 months after baseline
measure: Immune status
timeFrame: Baseline
measure: Immune status
timeFrame: Baseline
Secondary outcomes:
measure: Comparison of immune and virological statuses of early and late treatment groups
timeFrame: Baseline
measure: Viral reservoir : lymphocyte subpopulation
timeFrame: One year after baseline
measure: Viral reservoir : inductibility
timeFrame: One year after baseline
Other outcomes:
Locations:
city: Bondy
country: France
facility: Hôpital Jean Verdier
city: Colombes
country: France
facility: Hôpital Louis Mourier
city: Créteil
country: France
facility: Centre Hospitalier Intercommunal
city: Evry
country: France
facility: Centre hospitalier Francilien Sud
city: Le Kremlin Bicêtre
country: France
facility: Hôpital Bicêtre
city: Paris
country: France
facility: Groupe hospitalier Cochin Port Royal
city: Paris
country: France
facility: Groupe Hospitalier Necker
city: Paris
country: France
facility: Hôpital Robert Debré
city: Paris
country: France
facility: Hôpital Trousseau
city: Saint Denis
country: France
facility: Centre Hospitalier Général- Hôpital Delafontaine
city: Villeneuve Saint Georges
country: France
facility: Centre Hospitalier Général
Study officials:
References:
citation: Frange P, Montange T, Le Chenadec J, Batalie D, Fert I, Dollfus C, Faye A, Blanche S, Chace A, Fourcade C, Hau I, Levine M, Mahlaoui N, Marcou V, Tabone MD, Veber F, Hoctin A, Wack T, Avettand-Fenoel V, Warszawski J, Buseyne F. Impact of Early Versus Late Antiretroviral Treatment Initiation on Naive T Lymphocytes in HIV-1-Infected Children and Adolescents - The-ANRS-EP59-CLEAC Study. Front Immunol. 2021 Apr 22;12:662894. doi: 10.3389/fimmu.2021.662894. eCollection 2021.