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

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.

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.

Study Overview

• Status: Unknown
• Conditions: HIV Infection
• Intervention / Treatment: Other: Blood draw

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.

• Study Type: Interventional
• Enrollment (Anticipated): 80
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Bondy, France
    • Hôpital Jean Verdier
  • Colombes, France
    • Hôpital Louis Mourier
  • Créteil, France
    • Centre hospitalier intercommunal
  • Evry, France
    • Centre hospitalier Francilien Sud
  • Le Kremlin Bicêtre, France
    • Hôpital Bicêtre
  • Paris, France
    • Hôpital Trousseau
  • Paris, France
    • Hopital Robert Debre
  • Paris, France
    • Groupe Hospitalier Necker
  • Paris, France
    • Groupe hospitalier Cochin Port Royal
  • Saint Denis, France
    • Centre Hospitalier Général- Hôpital Delafontaine
  • Villeneuve Saint Georges, France
    • Centre Hospitalier Général

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 years to 18 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Early treatment group; 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
Other: Late treatment group; 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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: ANRS, Emerging Infectious Diseases

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: June 1, 2016
• Primary Completion (Anticipated): June 1, 2019
• Study Completion (Anticipated): June 1, 2019

Study Registration Dates

• First Submitted: January 13, 2016
• First Submitted That Met QC Criteria: February 2, 2016
• First Posted (Estimate): February 5, 2016

Study Record Updates

• Last Update Posted (Actual): January 18, 2019
• Last Update Submitted That Met QC Criteria: January 17, 2019
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; HIV Infections
• Other Study ID Numbers: ANRS EP 59 CLEAC