Longitudinal changes in plasma biomarkers of immune activation, neuronal inflammation and injury in persons with HIV initiating ART

Background Data on changes in biomarkers of brain health, and their associations with cognitive function in adults commencing either dual‐ or triple‐antiretroviral therapy (ART) are sparse. Methods Plasma biomarkers (neurofilament light [NfL], glial fibrillary acidic protein [GFAP], sCD14, CXCL10, neopterin and IL‐6) were measured at baseline and after 96 weeks on ART in individuals randomized to darunavir/ritonavir and either tenofovir‐DF/emtricitabine (triple‐ART, n = 119) or raltegravir (dual‐ART, n = 119) in NEAT‐001/ANRS143. Regression models examined associations of baseline and week‐96 biomarker concentrations with HIV clinical parameters, composite cognitive test scores (Standardized neuropsychological test [NPZ], 7‐domains) and treatment arm. Results In 238 individuals, median age was 38 (interquartile range [IQR] 31, 46) years, 87% male and 83% of white ethnicity. Baseline median log 10 HIV RNA 4.73 (IQR 4.23, 5.11) copies/mL and CD4 350 (IQR 285, 412) cells/mm 3 . At baseline, higher biomarker concentrations were associated with lower CD4 (NfL, GFAP, CXCL10; p < 0.03), higher log 10 HIV RNA (sCD14, neopterin, CXCL10; p < 0.02) and longer known duration of HIV (sCD14; p = 0.044). At week‐96, 94% had plasma HIV <50 copies/mL, and a decline in biomarker concentrations was observed: GFAP −14.4%, sCD14 −6.8%, neopterin −47.4%, CXCL10 −58.8%, IL‐6 −29.5% (all p < 0.001) and NfL −4.4% ( p = 0.075). NPZ improved by 0.21 mean points. Change in GFAP, CXCL10, sCD14, neopterin and NfL was negatively associated with change in CD4 (all p ≤ 0.002) but not change in NPZ ( p > 0.05). A greater decline in neopterin concentration was observed with dual‐ (−50.2%) versus triple‐ART (−44.3%; p = 0.022). Conclusions Plasma biomarkers of brain health improved following ART initiation, associated predominantly with improvements in CD4 count and partly with treatment arm.