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Objective   HIV ‐associated neurocognitive disorders ( HAND ) remain a challenge despite combination antiretroviral therapy ( cART ). Immune cell activation has been implicated to play a major role in the development of  HAND .    Methods  In this study, we used multicolor flow cytometry on peripheral blood ( PB ) and cerebrospinal fluid ( CSF ) samples to determine the expression of  HLA ‐ DR  and programmed death‐1 ( PD ‐1) on  CD 4+ and  CD 8+ T cells in patients with chronic  HIV  infection. Expression levels were correlated with  HI  virus load in  PB  and  CSF , classification of  HAND  and severity of magnetic resonance imaging ( MRI ) signal abnormalities.    Results  In a cohort of 86  HIV  patients we found that the grade of neurocognitive impairment and the severity of  MRI  signal abnormalities correlated with decreasing  CD 4/ CD 8‐ratios and increased frequencies of  HLA ‐ DR  expressing  CD 4+ and  CD 8+ T cells reaching the highest values in the  CSF  samples. Importantly,  HLA ‐ DR  upregulation was still detectable in virologically suppressed  HIV  patients. Further, T‐cell subpopulation analysis of 40  HIV  patients showed a significant shift from naïve to effector memory ( EM ) T cells that was negatively correlated with the grade of neurocognitive impairment in the  PB  samples. Moreover,  PD ‐1 was significantly increased on  CD 4+ memory T cells with highest levels on  EM  T cells in  HIV  patients with mild or severe neurocognitive alterations.    Interpretation  The  CD 4/ CD 8 ratio, the proportion of  EM  to naïve T cells and the immune activation profile of  CD 4+ and  CD 8+ T cells in  PB  and  CSF  might be useful parameters to monitor the efficacy of  cART  and to identify  HIV  patients at risk of further neurocognitive deterioration.

Neurocognitive decline in HIV patients is associated with ongoing T‐cell activation in the cerebrospinal fluid