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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: HIV Infections
• Intervention / Treatment: Biological: Blood sampling

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

• Study Type: Interventional
• Enrollment (Estimated): 451
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Mathurin C Tejiokem, Doctor; Phone Number: +237222231803; Email: tejiokem@pasteur-yaounde.org
• Study Contact Backup: Name: Albert Faye, Doctor; Phone Number: +33(0)140035361; Email: albert.faye@rdb.ap-hop-paris.fr

Study Locations

• Cameroon
  • Yaounde, Cameroon, 1274
    • Centre Pasteur Cameroun
    • Contact: Mathurin C Tejiokem; Phone Number: +237222231803; Email: tejiokem@pasteur-yaounde.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Health Services Research
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Children enrolled in Pediacam III ANRS12225 cohort	Biological: Blood sampling; Blood samples collected from children followed in the Pediacam III ANRS12225 cohort

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Level of pro-inflammatory and anti-inflammatory cytokines, chimiokines in the plasma	Measure of sCD14 (µg/ml). Levels of these biomarkers will be compared across all groups.	18 months
Level of pro-inflammatory and anti-inflammatory cytokines, chimiokines in the plasma	Measure of BAFF using luminex or commercially available ELISA quantification kits. Levels of these biomarkers will be compared across all groups.	18 months
Level of pro-inflammatory and anti-inflammatory cytokines, chimiokines in the plasma	Measure of CXCL13 using luminex or commercially available ELISA quantification kits. Levels of these biomarkers will be compared across all groups.	18 months
Level of pro-inflammatory and anti-inflammatory cytokines, chimiokines in the plasma	Measure of TNF-α (pg/ml). Levels of these biomarkers will be compared across all groups.	18 months
Level of pro-inflammatory and anti-inflammatory cytokines, chimiokines in the plasma	Measure of IL-10 (pg/ml). Levels of these biomarkers will be compared across all groups.	18 months
Level of pro-inflammatory and anti-inflammatory cytokines, chimiokines in the plasma	Measure of IP-10 (pg/ml). Levels of these biomarkers will be compared across all groups.	18 months
Level of pro-inflammatory and anti-inflammatory cytokines, chimiokines in the plasma	Measure of TRAIL (ng/ml). Levels of these biomarkers will be compared across all groups	18 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
- Humoral response to vaccines against tetanus, pertussis, and viral hepatitis B	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	18 months
- Functional and phenotypic characterization of B and T lymphocytes	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	18 months
- Size of the HIV reservoir	Measure total (copies/million PBMC), integrated (copies/million PBMC), unintegrated (copies/million PBMC) HIV DNA level in Peripheral Blood Mononuclear Cells (PBMC)	18 months
- Residual viremia in perinatally HIV-infected adolescent	Any detectable HIV-RNA below 50 copies/mL	18 months
- Level of HIV plasma p24	Measure plasma level of HIV p24 antigen (fg/ml) using ultrasentsitive technique called Simoa (Single molecule array)	18 months
- HLA phenotype and the KIR genotypes	HLA-B (27 et 57), HLA-B35 ou 53, HLA-C16:01+KIR2DL3+	18 months

Collaborators and Investigators

• Sponsor: ANRS, Emerging Infectious Diseases
• Collaborators: Hopital Universitaire Robert-Debre; Institut Pasteur; Université Paris-Sud; Centre Pasteur du Cameroun; Centre Mère et Enfant de la Fondation Chantal Biya; Centre Hospitalier D'essos; Hospital General De Douala; Centre Hospitalier Universitaire d'Orléans

Study record dates

Study Major Dates

• Study Start (Estimated): March 1, 2024
• Primary Completion (Estimated): August 30, 2025
• Study Completion (Estimated): August 30, 2025

Study Registration Dates

• First Submitted: August 24, 2023
• First Submitted That Met QC Criteria: March 7, 2024
• First Posted (Actual): March 12, 2024

Study Record Updates

• Last Update Posted (Actual): March 12, 2024
• Last Update Submitted That Met QC Criteria: March 7, 2024
• Last Verified: March 1, 2024

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; Urogenital Diseases; Genital Diseases; HIV Infections
• Other Study ID Numbers: ANRS 12414 PediacamNEG

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No