Central nervous system safety during brief analytic treatment interruption of antiretroviral therapy within four HIV remission trials: an observational study in acutely treated people living with HIV.

BACKGROUND The central nervous system (CNS) is a likely reservoir of HIV, vulnerable to viral rebound, inflammation, and clinical changes upon stopping antiretroviral therapy (ART). It is critical to evaluate the CNS safety of studies using analytic treatment interruption (ATI) to assess HIV remission. METHODS Thirty participants who started ART during acute HIV infection underwent CNS assessments across four ATI remission trials. ART resumption occurred with plasma viral load >1000 copies/mL. CNS measures included paired pre- vs. post-ATI measures of mood, cognitive performance, and neurologic examination, with elective cerebrospinal fluid (CSF) sampling, brain diffusion tensor imaging (DTI) and magnetic resonance spectroscopy (MRS). RESULTS Median participant age was 30 years old and 29/30 were male. Participants' median time on ART prior to ATI was 3 years, and ATI lasted a median of 35 days. Post-ATI, there were no differences in median mood scores or neurologic findings and cognitive performance improved modestly. During ATI, a low level of CSF HIV-1 RNA was detectable in six of 20 participants with plasma viremia, with no group changes in CSF immune activation markers or brain DTI measures. Mild worsening was identified in post-ATI basal ganglia total choline MRS, suggesting an alteration in neuronal membranes. CONCLUSION No adverse CNS effects were observed with brief, closely-monitored ATI in participants with acutely treated HIV, except a MRS alteration in basal ganglia choline. Further studies are needed to assess CNS ATI safety in HIV remission trials, particularly for studies using higher thresholds to restart ART and longer ATI durations.