Paediatric HIV infection from a mathematical perspective

Abstract

Background: Interventions aiming for an HIV cure would benefit from rapid elimination of virus after the onset of antiretroviral treatment (ART), by keeping the latent HIV reservoir small. Setting: We investigated HIV suppression in 312 perinatally infected infants starting ART within 6 months after birth from the EPPICC (European Pregnancy and Paediatric HIV Cohort Collaboration). Methods: To better understand kinetic differences in HIV suppression among infants, we investigated their individual viral loads (VL) decay dynamics. We identified VL decay patterns and determined times to viral suppression (TTS). For infants with strictly declining VLs (n=188), we used parameter fitting methods to estimate baseline VLs, decay rates and TTS. We subsequently identified the parameters determining TTS by linear modelling. Results: The majority of infants suppress HIV VL after the onset of ART. Some children experienced a long TTS due to an "erratic" VL decay pattern. We cannot exclude that this is partly due to treatment complications and subsequent treatment changes, but these children were characterised by significantly lower CD4 percentages (CD4%) at start of treatment compared to those with a "clean" VL decline. Focusing on this "clean" subset, the TTS could be predicted by mathematical modelling, and we identified baseline VL and CD4% as the major factors determining the TTS. Conclusion: As VL steeply increases and CD4% constantly decreases in untreated HIV-infected infants, the progression of an HIV infection is largely determined by these 2 factors. To prevent a further disease progression, treatment should be initiated early after contracting HIV, which consequently shortens TTS.