Vascular injury markers associated with cognitive impairment in people with HIV on suppressive antiretroviral therapy.
Title | Vascular injury markers associated with cognitive impairment in people with HIV on suppressive antiretroviral therapy. |
Publication Type | Journal Article |
Year of Publication | 2023 |
Authors | Guha, D, Misra, V, Yin, J, Horiguchi, M, Uno, H, Gabuzda, D |
Journal | AIDS |
Volume | 37 |
Issue | 14 |
Pagination | 2137-2147 |
Date Published | 2023 Nov 15 |
ISSN | 1473-5571 |
Keywords | Biomarkers, Chitinase-3-Like Protein 1, Cognitive Dysfunction, Cross-Sectional Studies, HIV, HIV Infections, Humans, Inflammation, Intercellular Adhesion Molecule-1, Interleukin-15, Interleukin-6, Interleukin-8, Middle Aged, Vascular Cell Adhesion Molecule-1, Vascular System Injuries |
Abstract | OBJECTIVE: Human immunodeficiency virus (HIV)-associated neurocognitive disorders (HAND) remain prevalent despite viral suppression on antiretroviral therapy (ART). Vascular disease contributes to HAND, but peripheral markers that distinguish vascular cognitive impairment (VCI) from HIV-related etiologies remain unclear.DESIGN: Cross-sectional study of vascular injury, inflammation, and central nervous system (CNS) injury markers in relation to HAND.METHODS: Vascular injury (VCAM-1, ICAM-1, CRP), inflammation (IFN-γ, IL-1β, IL-6, IL-8, IL-15, IP-10, MCP-1, VEGF-A), and CNS injury (NFL, total Tau, GFAP, YKL-40) markers were measured in plasma and CSF from 248 individuals (143 HIV+ on suppressive ART and 105 HIV- controls).RESULTS: Median age was 53 years, median CD4 + cell count, and duration of HIV infection were 505 cells/μl and 16 years, respectively. Vascular injury, inflammation, and CNS injury markers were increased in HIV+ compared with HIV- individuals ( P < 0.05). HAND was associated with increased plasma VCAM-1, ICAM-1, and YKL-40 ( P < 0.01) and vascular disease ( P = 0.004). In contrast, inflammation markers had no significant association with HAND. Vascular injury markers were associated with lower neurocognitive T scores in age-adjusted models ( P < 0.01). Furthermore, plasma VCAM-1 correlated with NFL ( r = 0.29, P = 0.003). Biomarker clustering separated HAND into three clusters: two clusters with high prevalence of vascular disease, elevated VCAM-1 and NFL, and distinctive inflammation profiles (CRP/ICAM-1/YKL-40 or IL-6/IL-8/IL-15/MCP-1), and one cluster with no distinctive biomarker elevations.CONCLUSIONS: Vascular injury markers are more closely related to HAND and CNS injury in PWH on suppressive ART than inflammation markers and may help to distinguish relative contributions of VCI to HAND. |
DOI | 10.1097/QAD.0000000000003675 |
Alternate Journal | AIDS |
PubMed ID | 37503603 |
PubMed Central ID | PMC10615701 |
Grant List | R01 DA046203 / DA / NIDA NIH HHS / United States U24 MH100929 / MH / NIMH NIH HHS / United States U24 MH100925 / MH / NIMH NIH HHS / United States U24 MH100928 / MH / NIMH NIH HHS / United States HHSN271201000036C / MH / NIMH NIH HHS / United States R01 MH110259 / MH / NIMH NIH HHS / United States U24 MH100930 / MH / NIMH NIH HHS / United States HHSN271201000030C / MH / NIMH NIH HHS / United States U24 MH100931 / MH / NIMH NIH HHS / United States |