Cerebrospinal Fluid Findings in Asymptomatic Adolescents on Long-term Antiretroviral Therapy After Perinatally Acquired HIV: An Exploratory Cross-sectional Study

Abstract

Abstract Background The extent and significance of subclinical cerebrospinal fluid (CSF) HIV-1 RNA detectability in adolescents with perinatally acquired HIV on long-term antiretroviral therapy (ART) are uncertain. We assessed CSF HIV-1 RNA, immunoglobulin G (IgG), and oligoclonal bands (OCBs) to explore CSF viral RNA detectability and associated immune activity. Methods We conducted an exploratory cross-sectional study of 40 adolescents aged 15–19 years with perinatally acquired HIV on long-term ART. Paired plasma and CSF samples were analyzed for HIV-1 RNA, CSF IgG, and OCBs. CSF viral escape was defined as detectable CSF HIV-1 RNA with concurrent plasma RNA <20 copies/mL. Correlations used Spearman's tests, and receiver operating characteristic analysis evaluated plasma thresholds predicting CSF detectability. Results Thirty-eight participants were included; 26/38 (68%) had plasma suppression. CSF viral escape occurred in 2/26 (7.7%) suppressed participants. Plasma and CSF viral loads correlated strongly (ρ = 0.87; P < .0001). ROC analysis showed an area under the curve of 0.93, with a plasma threshold of 24 copies/mL for CSF detectability. CSF IgG correlated with CSF HIV RNA (ρ = 0.46; P = .005). OCBs were type 1 in 70%, with type 4 mirror patterns more frequent at higher plasma viral loads. Conclusions Low-level CSF HIV-1 RNA was detectable in a minority of adolescents on long-term ART, including two with suppressed plasma viral load. Plasma and CSF HIV-1 RNA levels were strongly correlated. CSF IgG and OCB patterns may provide exploratory markers of immune activity, but these findings do not establish ongoing CNS viral replication or compartmentalized infection.