Clinical trial NCT05784584: Early Anti-Retroviral Treatment in HIV- Infected Children
Official title: A Prospective, Observational, Cohort, Multicenter Study of Early Anti-Retroviral Treatment in HIV- Infected Infants
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: HIV Infections
Keywords: HIV
Infection
Infants
Antiretroviral Therapy
Lead sponsor: PENTA Foundation
Sponsor class: NETWORK
First posted: 2023-03-27
Enrollment: 220
Sex: ALL
Maximum age (years): 180
Standard ages: CHILD
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Proportion of children with excellent HIV control
timeFrame: 4 years
Secondary outcomes:
Other outcomes:
Locations:
city: Bamako
country: Mali
facility: Centre Hospitalier Universitaire Gabriel Touré
city: Manica
country: Mozambique
facility: Centro de Investigaçao em Saude de Manhiça
city: Maputo
country: Mozambique
facility: Fundação Ariel Glaser contra o SIDA Pediátrico
city: Cape Town
country: South Africa
facility: Tygerberg Children's Hospital (TCH)
city: Durban
country: South Africa
facility: Africa Health Research Institute (AHRI)
city: Soweto
country: South Africa
facility: PHRU
Study officials:
affiliation: Fundación Investigación Hospital 12 de Octubre
name: Alfredo Tagarro, MD
role: STUDY_CHAIR
References: