What explains the poor contraction of the viral load during paediatric HIV infection?

Abstract

An acute HIV infection in young children differs markedly from that in adults: Children have higher viral loads (VL), and a poor contraction to a setpoint VL that is not much lower than the peak VL. As a result, children progress faster towards AIDS in the absence of treatment. We used a classical ordinary differential equation model for viral infection dynamics to study why children have a lower viral contraction ratio than adults. We performed parameter sweeps to identify factors explaining the observed difference between children and adults. We grouped parameters associated with the host, the infection, or the immune response. Based on paediatric data available from datasets within the EPIICAL project (https://www.epiical.org/), we refuted that viral replication rates differ between young children and adults, and therefore these cannot be responsible for the low VL contraction ratios seen in children. The major differences in lowering VL contraction ratio resulted from sweeping the parameters linked to the immune response. Thus, we postulate that an "ineffective" (late and/or weak) immune response is the most parsimonious explanation for the higher setpoint VL in young children, and hence the reason for their fast disease progression.