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 log10 HIV RNA 4.73 (IQR 4.23, 5.11) copies/mL and CD4 350 (IQR 285, 412) cells/mm3. At baseline, higher biomarker concentrations were associated with lower CD4 (NfL, GFAP, CXCL10; p < 0.03), higher log10 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.