Antiretroviral regimen and sex-specific metabolic heterogeneity in pediatric HIV.

Host metabolism is increasingly recognized as relevant in HIV remission and cure research yet remains understudied in children living with perinatally acquired human immunodeficiency virus (CLWH). The relation between clinical factors and plasma metabolic profiles, generated by untargeted ultra high-performance liquid chromatography/tandem mass spectrometry, of pre-pubescent, virally suppressed CLWH (n = 155) and uninfected controls (UCs, n = 155) was investigated. The specific antiretroviral treatment (ART) regimen dominated the plasma metabolic profile and significantly influenced metabolic sexual dimorphism in CLWH. Two CD4%-associated metabotypes among well-controlled CLWH on the same regimen suggested divergent, sub-clinical responses to ART. Phospholipids were most frequently able to predict HIV status independent of treatment regimen. Metabolic biomarkers are unlikely to reliably predict outcomes in CLWH across regimens, if not curated for ART-induced divergence. Thus, grouping of treated individuals in metabolic studies should be done with careful consideration for the ART regimen used.