Viral reservoir seeding and neurological metabolic dysregulation in early-life immunodeficiency virus infection

Background Viral reservoirs are rapidly established in peripheral and lymphoid tissues in HIV-exposed and infected infants, but the timing and consequence of viral seeding in the brain tissues remain unclear. Methods Based on previously collected samples, this study retrospectively examined early viral reservoir seeding in the brain, neuropathological alterations, and cerebrospinal fluid (CSF) metabolic changes in neonatal rhesus macaques infected with SIV at birth, with or without early initiation of antiretroviral therapy (ART). Results Viral RNA was detectable in CSF by 2 days post infection (dpi), paralleling plasma viral load, whereas brain tissue-associated viral DNA and RNA were not consistently detected until after 3 dpi. No significant neuropathological lesions or CSF proinflammatory responses were observed during the first week of infection. In contrast, profound CSF metabolic dysregulation emerged, which was largely reversed by early ART, particularly when initiated at 3 dpi. Conclusions These findings define the kinetics of brain viral reservoir seeding in neonates and highlight the critical importance of initiating ART within the earliest stages of infection to preserve brain development and function in children exposed to maternal HIV.