Children and adolescents growing up with perinatal HIV Long-term outcomes and comorbities

Perinatally acquired HIV (PHIV) progresses more rapidly than adult-acquired HIV and affects children during critical periods of immune and neurodevelopment. Although combination antiretroviral therapy (cART) has transformed PHIV into a manageable chronic condition, youth with PHIV remain at increased risk for neurocognitive, immune, metabolic, and cardiovascular complications. This thesis investigates long-term health outcomes, underlying mechanisms, and progression of comorbidities in PHIV youth on cART, using data from the NOVICE study and multi-omics approaches.
The results show that while plasma neurofilament light chain does not indicate active neuroaxonal injury, cognitive impairments persist over time. Multi-omics analyses reveal sustained immune activation, inflammation, and metabolic dysregulation (“inflammageing”), which likely contribute to neurocognitive deficits. Moreover, gut microbiome composition appears similar to matched controls, suggesting minimal microbiome alterations under effective cART. Lipidomic profiles and cardiometabolic markers, including lipoprotein(a), are largely comparable to uninfected peers, though specific cART regimens may influence lipid metabolism.
Overall, PHIV youth exhibit a complex interplay of persistent immune-metabolic disturbances and cognitive impairment, increasing long-term vulnerability to comorbidities. These findings underscore the need for longitudinal studies to further evaluate long-term outcomes, specifically cognitive and metabolic assessments, in PHIV youth to improve long-term health and to provide further insight into the underlying pathofysiology.