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Introduction: CD4/CD8 ratio is a marker of immune activation in HIV infection and has been associated with neurocognitive performance during chronic infection, but little is known about the early phases. The aim of this study was to examine the relationship between blood CD4/CD8 ratio and central nervous system endpoints in primary HIV infection (PHI) before and after antiretroviral treatment (ART). Methods: This was a retrospective analysis of the Primary Infection Stage CNS Events Study (PISCES) cohort. We longitudinally assessed blood and cerebrospinal fluid (CSF) markers of inflammation, immune activation and neuronal injury, and neuropsychological testing performance (NPZ4, an average of three motor and one processing speed tests, and a summarized total score, NPZ11, including also executive function, learning and memory) in ART‐naïve participants enrolled during PHI. Spearman correlation and linear mixed models assessed the relationships between the trajectory of CD4/CD8 ratio over time and neurocognitive performance, blood and CSF markers of immune activation and neuronal injury. Results: In all, 109 PHI participants were enrolled. The mean CD4/CD8 ratio decreased with longer time from infection to starting treatment (p < 0.001). Every unit increase in NPZ4 score was independently associated with a 0.15 increase in CD4/CD8 ratio (95% CI: 0.002–0.29; p = 0.047), whereas no correlation was found between CD4/CD8 ratio and NPZ11. Among the cognitive domains, only a change in processing speed was correlated with CD4/CD8 ratio over time (p = 0.03). The trajectory of the CD4/CD8 ratio was negatively correlated with change in CSF neurofilament light chain (p = 0.04). Conclusions: The trajectory of CD4/CD8 ratio was independently associated with motor/psychomotor speed performance, suggesting that immune activation is involved in brain injury during the early stages of the infection. [ABSTRACT FROM AUTHOR]

Since the advent of combination antiretroviral therapy (cART), HIV has transformed from a fatal disease to a chronic illness that often presents with milder central nervous system (CNS) symptoms laced with related confounders. The immune recovery associated with access to cART has led to a new spectrum of immune-mediated presentations of infection, phenotypically distinct from the conditions observed in advanced disease. HIV-associated neurocognitive disorder (HAND) entails a categorized continuum of disorders reflecting an array of clinical presentation, outcome, and increasing level of severity: asymptomatic neurocognitive impairment (ANI),mild neurocognitive disorder (MND), and HIV-associated dementia (HAD). HAND is defined through an assessment of neurocognitive abilities and functional performance. Progressive neurologic symptoms detected in patients on cART with detectable CSF viral load and a suppressed plasma viral load, or CSF viral load 1 log10 greater than low detectable plasma viral load, characterize a phenomenon termed symptomatic CSF "escape." CD8+ T-cell encephalitis, possibly a form of CNS immune reconstitution inflammatory syndrome, resembles CNS "escape" as it presents in patients despite viral suppression with cART. Cerebral toxoplasmosis, cryptococcal meningitis, and progressive multifocal leukoencephalopathy, are AIDS defining conditions with associated high mortality risk. Cerebral toxoplasmosis and cryptococcal meningitis typically manifest in immunosuppressed patients (<200 CD4+ T-cells/μL), while PML can occur in patients with higher CD4+ T-cell counts. Neurologic conditions are increasingly interconnected with chronic diseases, and classic opportunistic infections may have altered phenotypes in the cART era. However, there exist promising diagnostic methods and therapeutic approaches, as well as associated pitfalls in diagnosis and treatment. [ABSTRACT FROM AUTHOR]