Most EV proteins including inflammatory/immune response (ANXA, CRP, DPYSL2, ENO1, EZR, HLA, ITGB1, TIMP1), stress response (PARK7, PRDX2, SNCA, SNCB, SNCG, VIM), neuronal (NFASC, NPTN, NRXNs), astrocyte, (ALDH1L1, GFAP, GLUL, PEA15, S100B, SLC1A3) and CP (ATP1A1, ATP1A2, ATP1B1, ATP5B, CLIC6) markers were more abundant in subjects with versus without HAND, a finding that correlated with higher CSF EV concentrations and plasma VL in HAND. Here, ATP5F1B is linked to HIV-associated neurocognitive disorder.