Background: Plasma-based biomarkers offer a promising and accessible approach for detecting Alzheimer’s disease (AD), including in older people with HIV (PWH). Emerging evidence in the general population suggests that systemic inflammation may contribute to AD-related biomarker changes, but data in PWH remain limited. We previously demonstrated that elevated plasma p-tau217 and GFAP predict cognitive decline in this population. Given the persistence of immune activation despite viral suppression in PWH, we aimed to examine correlations between AD-related and inflammatory plasma biomarkers among older PWH.

Method: PWH aged ≥50 years with plasma HIV RNA <50 copies/mL from the HIV-NAT 006 cohort, an ongoing cohort of adults living with HIV in Bangkok, Thailand, were included. Plasma AD biomarkers (p-tau217, GFAP, and NfL) and inflammatory biomarkers (CXCL-9, hs-CRP, IL-6, sCD14, and TNFR1) were measured cross-sectionally using samples collected at the same study visit as cognitive assessments. All biomarker values were log-transformed. Cognitive function was assessed using the Thai-validated Montreal Cognitive Assessment (MoCA), with scores ≥25 considered normal.

Result: Among 255 participants (36.9% female; mean [SD] age, 55.9 [5.2] years; 76.1% had >6 years of education; mean duration of HIV infection, 17.9 [4.8] years), 61.2% had MoCA scores <25. Among AD biomarkers, GFAP was positively correlated with NfL (r = 0.467, p<0.001). CXCL-9 (r = 0.215, p = 0.001) and sCD14 (r = 0.229, p = 0.001) were positively correlated with NfL. TNFR1 was positively correlated with both GFAP (r = 0.249, p<0.001) and NfL (r = 0.440, p<0.001). P-tau217 showed statistically significant but weak correlations with NfL, CXCL-9, and TNFR1 (all |r| < 0.2) (Figure). Stratified analyses suggested that the strength of correlations between AD and inflammatory markers varied by cognitive status, with stronger correlations between CXCL-9 and TNFR1 with GFAP and NfL among PWH with MoCA scores <25.

Conclusion: These findings support a potential link between systemic inflammation and AD-related biomarkers in virally suppressed older PWH. Longitudinal studies are warranted to clarify the role of these inflammatory pathways in the trajectories of cognitive function among this population.