TY - JOUR
T1 - Central Nervous System Safety During Brief Analytic Treatment Interruption of Antiretroviral Therapy Within 4 Human Immunodeficiency Virus Remission Trials
T2 - An Observational Study in Acutely Treated People Living With Human Immunodeficiency Virus
AU - on behalf of the SEARCH 010/RV254 Study Group
AU - Hellmuth, Joanna
AU - Muccini, Camilla
AU - Colby, Donn J.
AU - Kroon, Eugène
AU - de Souza, Mark
AU - Crowell, Trevor A.
AU - Chan, Phillip
AU - Sacdalan, Carlo
AU - Intasan, Jintana
AU - Benjapornpong, Khunthalee
AU - Tipsuk, Somporn
AU - Puttamaswin, Suwanna
AU - Chomchey, Nitiya
AU - Valcour, Victor
AU - Sarnecki, Michal
AU - Tomaka, Frank
AU - Krebs, Shelly J.
AU - Slike, Bonnie M.
AU - Jagodzinski, Linda L.
AU - Dumrongpisutikul, Netsiri
AU - Sailasuta, Napapon
AU - Samboju, Vishal
AU - Michael, Nelson L.
AU - Robb, Merlin L.
AU - Vasan, Sandhya
AU - Ananworanich, Jintanat
AU - Phanuphak, Praphan
AU - Phanuphak, Nittaya
AU - Paul, Robert
AU - Spudich, Serena
N1 - Publisher Copyright:
© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved.
PY - 2021/10/1
Y1 - 2021/10/1
N2 - Background. The 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. Methods. Thirty 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). Results. Median 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. Conclusion. No 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.
AB - Background. The 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. Methods. Thirty 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). Results. Median 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. Conclusion. No 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.
KW - HIV
KW - HIV cure
KW - acute HIV infection
KW - analytic treatment interruption
KW - central nervous system
UR - http://www.scopus.com/inward/record.url?scp=85118283053&partnerID=8YFLogxK
U2 - 10.1093/cid/ciaa1344
DO - 10.1093/cid/ciaa1344
M3 - Article
C2 - 32916708
AN - SCOPUS:85118283053
SN - 1058-4838
VL - 73
SP - E1885-E1892
JO - Clinical Infectious Diseases
JF - Clinical Infectious Diseases
IS - 7
ER -