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Negative Serology by Immunoenzymatic Test (EIA) in HIV-infected Children Treated Early With Antiretroviral in the ANRS-Pediacam Study: Pathophysiological Mechanisms

Not Applicable
Recruiting
Conditions
HIV Infections
Interventions
Biological: Blood sampling
Registration Number
NCT06302933
Lead Sponsor
ANRS, Emerging Infectious Diseases
Brief Summary

The objective of the study is to identify the pathophysiological mechanisms responsible for the induction and maintenance of negative serologies by EIA tests in HIV-infected children treated early with HAART in the ANRS 12225-Pediacam III cohort in Cameroon

The hypothesis of better control of HIV infection through interactions between immunological, viral, and genetic factors was made to build the following objectives:

* Immunological aspect: lack of humoral response or immune activation

* Virological aspect: Reduced HIV reservoir size

* Determine the HLA phenotype in the different groups of children included and the KIR genotypes.

Detailed Description

There will be two phases of the study :

* A retrospective phase: case-control study The analyzed data are those collected previously or measured from the already available bio bank, within the framework of the Pediacam III cohort during the primary infection phase before the initiation of HAART, at 6 months after the end of the first series of EPI vaccines, and at 2 years.

* A prospective phase: cross-sectional study Based on an ad hoc bio bank created for parameters we couldn't measure on the existing bio bank

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
451
Inclusion Criteria

Case control study

  • Children included and followed in the ANRS 12225 study - Pediacam III
  • Having plasma samples in the bio bank during the above-mentioned periods Case:children with at least one negative HIV serology made by ELISA, permanent or transientduring follow-up.

Control (4 groups)

  • HIV-infected children with positive serology and viral load (VL) <400 copies /ml
  • HIV-infected children with positive serology and VL ≥400 copies / ml
  • HIV-uninfected children born to HIV-positive mothers
  • HIV-uninfected children born to HIV-uninfected mothers Selection of cases and controls will be matched on gestational age (premature <37, term ≥37 weeks) and year of birth (2007-2008 and 2009-2010).

Cross sectional study Inclusion criteria

  • All children still followed in the ANRS - Pediacam III cohort
  • Written consent of one of the parents or the guardian and assent of the child if aged ≥ 11 years and complete disclosure of HIV statusfor infected children for participation to the study.
Exclusion Criteria
  • Refusal by one of the parents or the guardian for the child's participation in the study
  • No assent of the child (if aged ≥ 11 years and with complete disclosure of HIV status, for infected children)

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Children enrolled in Pediacam III ANRS12225 cohortBlood sampling-
Primary Outcome Measures
NameTimeMethod
Level of pro-inflammatory and anti-inflammatory cytokines, chimiokines in the plasma18 months

Measure of TRAIL (ng/ml). Levels of these biomarkers will be compared across all groups

Secondary Outcome Measures
NameTimeMethod
- Size of the HIV reservoir18 months

Measure total (copies/million PBMC), integrated (copies/million PBMC), unintegrated (copies/million PBMC) HIV DNA level in Peripheral Blood Mononuclear Cells (PBMC)

- Residual viremia in perinatally HIV-infected adolescent18 months

Any detectable HIV-RNA below 50 copies/mL

- Level of HIV plasma p2418 months

Measure plasma level of HIV p24 antigen (fg/ml) using ultrasentsitive technique called Simoa (Single molecule array)

- Humoral response to vaccines against tetanus, pertussis, and viral hepatitis B18 months

Serum concentrations of human IgG antibodies against tetanus-toxoid, pertussis, and viral hepatitis B will be measured using commercially available ELISA quantification kits and results will be given as IU/mL

- Functional and phenotypic characterization of B and T lymphocytes18 months

Level (cells/μL or percentage) of T and B-cell lymphocytes subpopulations will be assess in blood using flow cytometry. Functional characterization of T and B lymphocytes will be done by cell culture following by cytokine production titration

- HLA phenotype and the KIR genotypes18 months

HLA-B (27 et 57), HLA-B35 ou 53, HLA-C16:01+KIR2DL3+

Trial Locations

Locations (3)

Hôpital de Jour - Hôpital Laquintinie de Douala

🇨🇲

Douala, Cameroon

Unité Pédiatrique de Jour - Centre Mère et Enfant de la Fondation Chantal Biya

🇨🇲

Yaounde, Cameroon

Service de Pédiatrie - Centre Hospitalier d'Essos

🇨🇲

Yaoundé, Cameroon

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