ENABLE

Early ARV treatment in sub-Saharan Africa (SSA) reaches only approximately 50% of infants born with HIV. Mortality in infants in the first 12 months after diagnosis is still over 10% in early treated infants diagnosed at birth, 25% in infants diagnosed with opportunistic infections. According to our experience, the probability of virological control 1 year after diagnosis is only 25 to 35%, even after the rollout of dolutegravir (DTG). As a solution for this problem, we propose the addition of four shots of subcutaneous (SC), long-half-life broadly neutralizing antibodies (bNAbs) at diagnosis, and 3, 6 and 9 months after diagnosis, as an add-on to standard oral ART will provide immediate therapeutic benefit and decrease HIV viral load levels in the most critical period of life of children with HIV, allowing for a decreased risk of co-infections, HIV-encephalopathy and death. We will evaluate for the first time the efficacy of combining two bNAbs (ePGT121v1-LS and VRC07-523-LS, as intensification therapy for ART, to achieve viral suppression within one year after diagnosis in high risk-infants with HIV. The specific aims to achieve this general aim will be: to perform a phase II/III trial with bNAbs, capacity strengthening related with bNAbs in Africa, to characterize biomarkers for anticipating response to bNAbs, to identify the barriers and facilitators of rollout of bNAbs as a treatment, and to liaise with relevant stakeholders The pathway to achieve this aim will be a collaborative framework between a scientific network with partners in several SSA countries, producers of bNAbs, and European and African laboratories. With this approach, the probability of viral suppression 1 year after diagnosis will be increased from 30% to 95% to achieve 2030 UNAIDS 3rd target. This achievement will impact in a reduction of HIV- associated morbidity and mortality in the first year of life and beyond in more than 130 000 infants every year.