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

Abstract 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.