Evidence map›Paper›PMID 32916708›Full record

Observational studyClinical infectious diseases : an official publication of the Infectious Diseases Society of America2021

Central Nervous System Safety During Brief Analytic Treatment Interruption of Antiretroviral Therapy Within 4 Human Immunodeficiency Virus Remission Trials: An Observational Study in Acutely Treated People Living With Human Immunodeficiency Virus.

Joanna Hellmuth, Camilla Muccini, Donn J Colby, Eugène Kroon, Mark de Souza, Trevor A Crowell, Phillip Chan, Carlo Sacdalan, Jintana Intasan, Khunthalee Benjapornpong and 20 more

Open access · greenAbstract readObservational Study
In one paragraph

Observational study in Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
1.2field-weighted citation impact, top 21% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed, 12 citations in OpenAlex.

  1. Review
  2. Article
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  4. Review
  5. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

30 authors at 10 institutions in 4 countries.

Joanna HellmuthMemory and Aging Center, Department of Neurology, University of California, San Francisco, California, USA.ORCID 0000-0002-7577-4196
Camilla MucciniSEARCH, The Thai Red Cross AIDS Research Centre, Bangkok, Thailand.
Donn J ColbySEARCH, The Thai Red Cross AIDS Research Centre, Bangkok, Thailand.
Eugène KroonSEARCH, The Thai Red Cross AIDS Research Centre, Bangkok, Thailand.
Mark de SouzaSEARCH, The Thai Red Cross AIDS Research Centre, Bangkok, Thailand.
Trevor A CrowellHenry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, Maryland, USA.
Phillip ChanSEARCH, The Thai Red Cross AIDS Research Centre, Bangkok, Thailand.
Carlo SacdalanSEARCH, The Thai Red Cross AIDS Research Centre, Bangkok, Thailand.
Jintana IntasanSEARCH, The Thai Red Cross AIDS Research Centre, Bangkok, Thailand.
Khunthalee BenjapornpongSEARCH, The Thai Red Cross AIDS Research Centre, Bangkok, Thailand.
Somporn TipsukSEARCH, The Thai Red Cross AIDS Research Centre, Bangkok, Thailand.
Suwanna PuttamaswinSEARCH, The Thai Red Cross AIDS Research Centre, Bangkok, Thailand.
Nitiya ChomcheySEARCH, The Thai Red Cross AIDS Research Centre, Bangkok, Thailand.
Victor ValcourMemory and Aging Center, Department of Neurology, University of California, San Francisco, California, USA.
Michal SarneckiJanssen Vaccines, Bern, Switzerland.
Frank TomakaJanssen Research & Development LLC, Titusville, NJ, USA.
Shelly J KrebsHenry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, Maryland, USA.
Bonnie M SlikeHenry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, Maryland, USA.
Linda L JagodzinskiU.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.
Netsiri DumrongpisutikulFaculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
Napapon SailasutaDepartment of Tropical Medicine, Medical Microbiology and Pharmacology, University of Hawaii, Honolulu, Hawaii, USA.
Vishal SambojuMemory and Aging Center, Department of Neurology, University of California, San Francisco, California, USA.
Nelson L MichaelU.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.
Merlin L RobbHenry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, Maryland, USA.
Sandhya VasanHenry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, Maryland, USA.
Jintanat AnanworanichHenry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, Maryland, USA.
Praphan PhanuphakSEARCH, The Thai Red Cross AIDS Research Centre, Bangkok, Thailand.
Nittaya PhanuphakSEARCH, The Thai Red Cross AIDS Research Centre, Bangkok, Thailand.
Robert PaulMissouri Institute of Mental Health, University of Missouri-St. Louis, Missouri, USA.
Serena SpudichYale University, New Haven, Connecticut, USA.
Thai Red Cross Society · THHenry M. Jackson Foundation · USUniversity of California, San Francisco · USWalter Reed Army Institute of Research · USChulalongkorn University · THJanssen (Switzerland) · CHJanssen (United States) · USUniversity of Hawaii System · USUniversity of Missouri–St. Louis · USYale University · US

Funding

Yale Clinical and Translational Science Award (U Component)UL1TR001863 · NCATS · YALE UNIVERSITY · PI John H. Krystal, LUCILA OHNO-MACHADO · 2016 to 2026
$102.9M
Virology CoreP30AI027763 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI STEVEN Grant DEEKS · 1988 to 2026
$93.6M
Long-Term CNS Consequences of Treatment During Acute InfectionR01MH095613 · NIMH · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI SPUDICH, SERENA S, VALCOUR, VICTOR · 2011 to 2015
$3.1M
Evaluation of the Interplay between HIV and COVID-19 in a large urban safety-net HIV clinicR01AI158013 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI GANDHI, MONICA, SPINELLI, MATTHEW A. · 2020 to 2023
$3.1M
Impact of Treatment on Brain Integrity in the Earliest Stages of HIV InfectionR01MH113560 · NIMH · UNIVERSITY OF MISSOURI-ST. LOUIS · PI PAUL, ROBERT HARRIS, VALCOUR, VICTOR · 2017 to 2021
$3.1M
Therapeutic Interventions during Acute Infection to Address the CNS Reservoir forR01NS084911 · NINDS · YALE UNIVERSITY · PI ANANWORANICH, JINTANAT, SPUDICH, SERENA S · 2013 to 2017
$2.3M
Defining the clinical utility of CSF biomarkers of neurodegeneration in HIV+ eldersK23MH114724 · NIMH · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI HELLMUTH, JOANNA · 2017 to 2020
$796k
NCATS NIH HHS UL1 TR001863NIAID NIH HHS P30 AI027763NIAID NIH HHS R01 AI158013NIMH NIH HHS K23 MH114724NIMH NIH HHS R01 MH095613NIMH NIH HHS R01 MH113560NINDS NIH HHS R01 NS084911
6 · The paper itself

Abstract

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.

Indexed as

HIV InfectionsAdultAnti-Retroviral AgentsCentral Nervous SystemDiffusion Tensor ImagingHIVHumansMaleViral LoadAnti-Retroviral Agentsacute HIV infectionanalytic treatment interruptioncentral nervous systemHIVHIV cure

Identifiers

PMID32916708
PMCPMC8492357
OpenAlexW3086740068

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.