Neurocognitive effects of latent <i>Toxoplasma gondii</i> infection in immunocompromised people with HIV

<i>Toxoplasma gondii</i> (<i>T. gondii</i>) is a neurotropic parasite that establishes latent infection in the central nervous system (CNS), and may alter behaviour and contribute to neuronal dysfunction. However, its impact on cognitive performance and CNS pathophysiological alterations in people with HIV (PWH) remains unclear. A cross-sectional study of adult PWH was conducted, assessing latent <i>T. gondii</i> infection through serum IgG levels in the absence of neurotoxoplasmosis. Neurocognitive impairments were assessed through neurocognitive testing across 6 domains, along with depressive and anxiety symptoms evaluation, and educational attainment. CNS pathophysiological alterations were assessed through amyloid-β1-42, total tau, phosphorylated tau, neopterin, and S-100β quantification in cerebrospinal fluid (CSF). Fifty-eight PWH were included, and <i>T. gondii</i> seropositivity was detected in 46.5% of participants (27/58). Overall, cognitive performance was largely comparable between groups, although subtle, non-significant declines were observed across several domains. <i>T. gondii</i>-seropositive individuals demonstrated a faster completion of Trail Making Test Part B (<i>β</i> = -35.79 sec; 95% CI: -67.78 to -3.86), lower educational attainment (<i>β</i> = -1.92 years; 95% CI: -3.76 to -0.09), without different levels of CSF biomarkers for neuronal-synaptic degeneration, Alzheimer's pathology, beta-amyloid deposition, macrophage-derived inflammation and glial activation-degeneration. In PWH with low CD4 counts, latent <i>T. gondii</i> infection was not associated with overt cognitive impairment or detectable CNS pathophysiological alterations. Instead, an atypical profile emerged, combining faster task-switching with lower educational attainment and subtle, non-significant declines in other domains. These findings highlight the complex nature of <i>T. gondii</i>-host interactions and need for longitudinal studies to clarify long-term neurocognitive outcomes.