Antiretroviral therapy has revolutionized survival. With access to antiretroviral treatment, increasing numbers of children are surviving into adolescence and beyond. Advances in treatment have encouraged the optimistic idea that a ‘cure’ of HIV infection is possible by reducing the HIV reservoir to a level that could maintain HIV ‘remission’ after treatment interruption.
However, only a very small minority of patients achieve prolonged viral control after treatment interruption, with early antiretroviral treatment as a single interventional strategy. The mechanisms of post-treatment control require further characterization.
Of the estimated 38 million people living with HIV worldwide in 2019, about 1.3 million were pregnant women and 2.8 million were children. Among them, about 15 per cent of pregnant women and close to 50 per cent of children and adolescents are not on life-saving HIV treatment.
In line with international guidelines, perinatally HIV-infected infants should start antiretroviral treatment as soon as the diagnosis is confirmed, and currently should remain on therapy for their whole life. This increases the risk of accumulating toxicity and viral resistance. If their adherence to treatment is poor, the rate of virological failure increases over time.
There is an urgent need to define strategies, such as therapeutic HIV vaccines, to provide long-term viral suppression in the paediatric population, in order to permit safe treatment interruption without viral rebound and its associated complications.
In response, the EPIICAL international consortium has been established, gathering together scientists and clinicians in the field of paediatric HIV infection. We believe that perinatally infected children treated with suppressive antiretroviral therapy from early infancy represent the optimal population model in which to study novel immunotherapeutic strategies aimed at achieving ART-free remission.
THE OVERALL GOAL OF EPIICAL IS TO WORK COLLABORATIVELY IN ESTABLISHING NEW, EARLY SCIENTIFIC EFFORTS LEADING TO TREATMENTS FOR HIV REMISSION IN CHILDREN
In the phase 2016-2020 (Early-treated Perinatally HIV-infected Individuals: Improving Children’s Actual Life with Novel Immunotherapeutic Strategies), the EPIICAL Consortium successfully designed and conducted studies in children living with HIV, by establishing different well-characterized cohorts both in Europe and Africa. Specifically, it has:
- established a predictive in vitro and in vivo platform to inform treatment strategies leading to HIV remission and,
- evaluated strategies to optimize the management of children who are infected with HIV before and after birth.
In this new phase 2020-2024 (Novel Strategies to induce long-term viral remission in Early Treated HIV infected Children), we want to carry on the mission of EPIICAL through:
- follow-up of CARMA and EARTH, the cohorts of early treated HIV infected children that EPIICAL has established in Phase I, and recruitment of new cohorts
- a retention strategy in the EPIICAL studies, based on the analysis and understanding of adherence issues with children and adolescents on antiretrovirals
- innovation of the current methodological approaches to HIV research by adding cutting-edge technologies, such as epigenetic studies, RNA sequencing and evaluation of the Humoral Immunity.
The renewed Project, EPIICAL 2020-2024 started in February 2020 and comprises 27 partners, who are active in four Working Groups (WG):
- WG 1: Implementation of Early treated cohorts of HIV infected children and Retention strategies
- WG 2: Identification of Novel endpoints through the characterization of Early treated cohorts – Immunological Platform
- WG 3: Identification of Novel endpoints through the characterization of Early treated cohorts – Virological platform
- WG 4: Regulatory, Data Analysis, Communication, Management