icon-    folder.gif   Conference Reports for NATAP  
  Conference on Retroviruses
and Opportunistic Infections
Will be Virtual
Boston USA
March 6-10, 2021
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  CROI 2021 March 6-10 Reported by Jules Levin
Debjani Guha1, Vikas Misra1, Sukrutha Chettimada1, David Lorenz1, Dana Gabuzda1
1Dana-Farber Cancer Institute, Boston, MA, USA
Background: HIV-associated neurocognitive disorders (HAND) remain prevalent despite viral suppression on current antiretroviral therapy (ART). Cerebrovascular disease contributes to HAND, but biomarkers that distinguish vascular cognitive impairment from other types of HAND remain unclear. In this cross-sectional study, we investigated relationships between plasma and CSF vascular, inflammation, and CNS injury markers, HAND, and cerebrovascular disease in HIV+ subjects on ART.
Methods: Vascular injury (ICAM-1, VCAM-1, CRP), inflammation (IFN-γ, IL-1β, IL-6, IL-8, IL-15, IP-10, MCP-1, VEGF-A), and CNS injury (total Tau, GFAP, YKL-40) markers were measured in plasma and CSF samples collected from subjects enrolled in NNTC and CHARTER between 2006-2015 using the Meso Scale Discovery (MSD) platform in 207 subjects (143 HIV+ virally suppressed on ART, age 30-75 years, 85% male, 71% white, 73 with HAND diagnoses of asymptomatic neurocognitive impairment (ANI) or mild neurocognitive disorder (MND) and 70 without HAND, and 64 HIV- controls matched for age, gender, race). CSF and plasma albumin levels were measured and CSF-plasma albumin ratio (Qalb) was calculated.
Results: The median age of HIV+ participants was 52 years (IQR 47 - 58) and median CD4 count, CD4 nadir, plasma viral load, and duration of HIV infection were 504 cells/ul, 76 cells/ul, 50 HIV copies/ml, and 16.5 years, respectively. HIV+ subjects had higher ICAM-1, CRP, IL-8, IL-15, IP-10, and VEGF in plasma and higher CRP, IP-10, VEGF, and GFAP in CSF compared with HIV- controls (p<0.05). Plasma ICAM-1, VCAM-1, CRP, and YKL-40 and CNS injury markers (CSF total Tau, GFAP, YKL-40) were increased in HAND vs. no HAND or HIV- control groups and correlated negatively with neurocognitive T scores (p<0.05). In contrast, most inflammation markers had weak or no significant associations with HAND and T scores. Cerebrovascular disease was more prevalent among HAND compared with no HAND subjects, and was associated with increased levels of VCAM1 and YKL-40 in plasma and increased total Tau and YKL-40 in CSF (p<0.05). We did not detect significant associations between Qalb and plasma or CSF biomarkers.
Conclusion: Peripheral markers of vascular injury are more closely related to HAND and CNS injury in HIV patients on current ART than markers of inflammation, and may help to distinguish relative contributions of vascular cognitive impairment to HAND in this population.