Early Anti-Retroviral Treatment in HIV- Infected Children

A Prospective, Observational, Cohort, Multicenter Study of Early Anti-Retroviral Treatment in HIV- Infected Infants

EARTH study is conducted as part of the EPIICAL project. It is a prospective cohort study which aims to monitor clinical, virological and immunological features of HIV-positive, early treated children (≤90 days after diagnosis), in order to identify participants with excellent viral and immunological control, and also other without excellent control, in order to stratify potential participants in proof-of-concept trials directed to HIV cure.

Study Overview

• Status: Active, not recruiting
• Conditions: HIV Infections
• Intervention / Treatment: Procedure: Blood samples collection

Detailed Description

The duration of the study is 4 years from the start of enrollment with at least 4 years of follow-up for each participant. The study is conducted in South Africa, Mali, and Mozambique with an expected enrollment target of 200 participants (as a minimum). In this study, newly diagnosed HIV-infected children will start ART as early as possible, following local standards of care, and will be followed up to 4 years of age. Clinical and blood data for viral load, immunology, and serology will be collected at the 11 visits. HIV reservoir size and HIV-specific immune responses will be analyzed at visit 1 and at 1, 2, 3, and 4 years after enrollment. We will identify children with HIV infection eligible to participate in proof-of-concept treatment/remission studies.

A predictive model developed from European participant data will help identify children with low reservoir. These predictions will then be compared with available data from participants already enrolled with an excellent control to refine the model.

• Study Type: Observational
• Enrollment (Actual): 220

Contacts and Locations

Study Locations

• Mali
  • Bamako, Mali
    • Centre Hospitalier Universitaire Gabriel Touré
• Mozambique
  • Manica, Mozambique
    • Centro de Investigaçao em Saúde de Manhiça
  • Maputo, Mozambique
    • Fundação Ariel Glaser contra o SIDA Pediátrico
• South Africa
  • Cape Town, South Africa
    • Tygerberg Children's Hospital (TCH)
  • Durban, South Africa
    • Africa Health Research Institute (AHRI)
  • Soweto, South Africa
    • PHRU

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 second to 5 months (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Perinatally infected infants who begin ART ≤ 90 days after diagnosis. Breastfed infants diagnosed with HIV ≤90 days of age and starting ART ≤ 90 days after diagnosis.

The diagnosis of HIV transmission by breastmilk will be made from infants who:

1. Have a negative birth HIV PCR
2. Are being breastfed
3. Who subsequently have 2 molecular methods positive for HIV. These tests will be conducted selectively among participants with a clinical evaluation suggestive of HIV infection, at the discretion of the attending physician.

Description

Inclusion Criteria:

1. Perinatally infected infants who start ART at ≤90 days after diagnosis (HIV infection diagnosed and confirmed by molecular methods in 2 different samples, i.e., positive qualitative HIV DNA/RNA test).
2. Breastfed-infected children found to be infected ≤ 90 days of age and who started ART at < 90 days after diagnosis. This group will be younger than six months of age at ART initiation.
3. Caregivers (mother, if alive and available) able to provide informed consent.
4. Able to take ART.

Exclusion Criteria:

1. Second and successive RNA PCR negative
2. Malignancy
3. Current concomitant immunosuppressive therapy (including>15 days and >2 mg/kg/day of prednisone-equivalent).
4. Caregivers withdraw consent
5. Age >180 days.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Infants infected through breast-feeding and perinatally; Infants infected through breast-feeding and perinatally diagnosed with HIV ≤90 days of age and starting ART ≤90 days after diagnosis. For these patients clinical data and blood for viral load, immunology and serology will be collected in the 11 visits.	Procedure: Blood samples collection; The study population will take blood samples for virological and immunological measurements.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of children with excellent HIV control	Proportion of children with excellent HIV control profile at 2 and 4 years of age. This excellent control profile includes a composite endpoint of all of the following: Undetectable HIV RNA viral load in peripheral blood in the last year (blips, spikes and suboptimal viral control allowed, see below for definitions),; Reservoir size (Total DNA /million PBMC) below 25th percentile with ddPCR / IPDA.; Good immunological control (defined as a CD4 >30% and a good NK or CTL response) during the last year	4 years

Collaborators and Investigators

• Sponsor: PENTA Foundation
• Investigators: Study Chair: Alfredo Tagarro, MD, Fundación Investigación Hospital 12 de Octubre

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2018
• Primary Completion (Anticipated): February 28, 2024
• Study Completion (Anticipated): February 28, 2024

Study Registration Dates

• First Submitted: March 2, 2023
• First Submitted That Met QC Criteria: March 13, 2023
• First Posted (Actual): March 27, 2023

Study Record Updates

• Last Update Posted (Actual): March 27, 2023
• Last Update Submitted That Met QC Criteria: March 13, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: Infection; HIV; Infants; Antiretroviral Therapy
• 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: EARTH

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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