Central Nervous System Safety During Brief Analytic Treatment Interruption of Antiretroviral Therapy Within 4 Human Immunodeficiency Virus Remission Trials

Autor: Vishal Samboju, Joanna Hellmuth, Bonnie M. Slike, Nitiya Chomchey, Jintanat Ananworanich, Michal Sarnecki, Frank Tomaka, Camilla Muccini, Phillip Chan, Carlo Sacdalan, Serena Spudich, Mark de Souza, Jintana Intasan, Sandhya Vasan, Linda L. Jagodzinski, Khunthalee Benjapornpong, Suwanna Puttamaswin, Eugene Kroon, Netsiri Dumrongpisutikul, Praphan Phanuphak, Somporn Tipsuk, Donn J Colby, Nelson L. Michael, Shelly J. Krebs, Victor Valcour, Napapon Sailasuta, Trevor A Crowell, Nittaya Phanuphak, Merlin L. Robb, Robert H. Paul
Přispěvatelé: Graduate School, AII - Infectious diseases, APH - Aging & Later Life, Global Health
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: Clin Infect Dis
Clinical infectious diseases, 73(7), e1885-e1892. Oxford University Press
ISSN: 1058-4838
Popis: BackgroundThe central nervous system (CNS) is a likely reservoir of human immunodeficiency virus (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.MethodsThirty participants who started ART during acute HIV infection underwent CNS assessments across 4 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).ResultsMedian participant age was 30 years old and 29/30 were male. Participants’ median time on ART before 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 6 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.ConclusionNo adverse CNS effects were observed with brief, closely monitored ATI in participants with acutely treated HIV, except an 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.
Databáze: OpenAIRE