Residual Central Nervous System Immune Activation Is Not Prevented by Antiretroviral Therapy Initiated During Early Chronic HIV Infection

BACKGROUND: Antiretroviral therapy (ART) initiated during acute infection can potentially impact the central nervous system (CNS) reservoir, but the differential long-term effects of ART initiation during early or late chronic infection are unknown. METHODS: We included neuroasymptomatic people with human immunodeficiency virus (HIV) with suppressive ART initiated during chronic (>1 year since transmission) HIV with archived cerebrospinal fluid (CSF) and serum samples after 1 and/or ≥3 years of ART from a cohort study. CSF and serum neopterin was measured using a commercial immunoassay (BRAHMS, Germany). RESULTS: In total, 185 people with HIV (median, 79 [interquartile range, 55–128] months on ART) were included. A significant inverse correlation was found between CD4(+) T-cell count and CSF neopterin only at baseline (r = −0.28, P = .002), but not after 1 (r = −0.026, P = .8) or ≥3 (r −0.063, P = .5) years of ART. No significant differences were seen in CSF or serum neopterin concentrations between different pretreatment CD4(+) T-cell strata after 1 or ≥3 (median, 6.6) years of ART. CONCLUSIONS: In people with HIV initiating ART during chronic infection, occurrence of residual CNS immune activation was not correlated with pretreatment immune status, even when treatment was initiated at high CD4(+) T-cell counts, suggesting that the CNS reservoir, once established, is not differentially affected by the timing of ART initiation during chronic infection.