Evidence map›Paper›PMID 31045650›Full record

ArticleJournal of acquired immune deficiency syndromes (1999)2019

Immunological and Neurometabolite Changes Associated With Switch From Efavirenz to an Integrase Inhibitor.

Archana Asundi, Yvonne Robles, Tyler Starr, Alan Landay, Jennifer Kinslow, Joshua Ladner, Laura White, Rebeca M Plank, Kathleen Melbourne, Daniel Weisholtz and 6 more

Open access · greenAbstract read
In one paragraph

Article in Journal of acquired immune deficiency syndromes (1999), 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
0.9field-weighted citation impact, top 30% 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

9 citing papers in PubMed, 18 citations in OpenAlex.

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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

16 authors at 5 institutions in 1 country.

Archana AsundiDivision of Infectious Diseases, Boston Medical Center, Boston, MA.
Yvonne RoblesDivision of Infectious Diseases, Brigham and Women's Hospital, Boston, MA.
Tyler StarrDepartment of Radiology, Brigham and Women's Hospital, Boston, MA.
Alan LandayDepartment of Microbial Pathogens and Immunity, Rush Medical College, Chicago, IL.
Jennifer KinslowDepartment of Microbial Pathogens and Immunity, Rush Medical College, Chicago, IL.
Joshua LadnerDepartment of Radiology, Brigham and Women's Hospital, Boston, MA.
Laura WhiteDepartment of Biostatistics, Boston University, Boston MA.
Rebeca M PlankDivision of Infectious Diseases, Brigham and Women's Hospital, Boston, MA.
Kathleen MelbourneGilead Sciences, Foster City, CA.
Daniel WeisholtzDepartment of Neurology, Brigham and Women's Hospital, Boston, MA.
Monica BennettDepartment of Psychiatry, Brigham and Women's Hospital, Boston, MA.
Hong PanDepartment of Radiology, Brigham and Women's Hospital, Boston, MA.
Emily SternDepartment of Radiology, Brigham and Women's Hospital, Boston, MA.
Alexander LinDepartment of Radiology, Brigham and Women's Hospital, Boston, MA.
Daniel R KuritzkesDivision of Infectious Diseases, Brigham and Women's Hospital, Boston, MA.
Nina H LinDivision of Infectious Diseases, Boston Medical Center, Boston, MA.
Brigham and Women's Hospital · USBoston University · USBoston Medical Center · USGilead Sciences (United States) · USHarvard University · US

Funding

Translational ScienceP30AI042853 · NIAID · MIRIAM HOSPITAL · PI CURT G BECKWITH · 1998 to 2026
$51.7M
NIAID NIH HHS P30 AI042853
6 · The paper itself

Abstract

backgroundThe biological mechanisms by which efavirenz (EFV) causes central nervous system (CNS) effects are unclear. The objective of this pilot study was to elucidate the mechanisms underlying these CNS effects by correlating well-described neuropsychological (NP) changes with neurometabolites and immunologic markers following switch off EFV.

settingTwo single-arm parallel switch studies among HIV-infected adults in Boston, USA, from 2015 to 2017.

methodsTwenty asymptomatic HIV-infected adults on EFV-containing regimens were switched to an integrase strand transfer inhibitor-based regimen for 8 weeks. NP assessments were conducted before and after switch and correlated with neurometabolite changes measured using magnetic resonance spectroscopy and immunological markers. All pre-EFV and post-EFV measures were evaluated using matched-paired analyses.

resultsNP testing demonstrated improvement in the domains of mood, cognition, and sleep off EFV. Magnetic resonance spectroscopy revealed decreases in the neurometabolite glutathione level (P = 0.03), a marker of oxidative stress after switch. Inhibitory neuronal activity as reflected by gamma-amino butyric acid levels increased (P = 0.03), whereas excitatory neurotransmitters glutamine + glutamate (Glx) and aspartate decreased (P = 0.04, 0.001). Switching off EFV was also associated with changes in inflammatory markers; plasma markers sCD14 (P = 0.008) decreased, whereas I-FABP and TNFRI levels increased (P = 0.05, 0.03). Cellular markers CD4 and CD8 HLA-DR-/CD38 subsets both increased (P = 0.05, 0.02).

conclusionsEven asymptomatic participants showed improvements in NP parameters when switched off EFV. These improvements were associated with decreased CNS oxidative stress and excitatory neuronal activity. Changes in immune activation biomarkers suggested overall decreased inflammation. EFV may exert CNS effects through oxidative and inflammatory pathways, providing insight into possible mechanisms of EFV neurotoxicity.

Indexed as

AdultAlkynesAnti-HIV AgentsBenzoxazinesBiomarkersBostonCentral Nervous SystemCyclopropanesFemalegamma-Aminobutyric AcidGlutamic AcidGlutamineGlutathioneHIV InfectionsHIV Integrase InhibitorsHumansAlkynesAnti-HIV AgentsBenzoxazinesBiomarkersCyclopropanesefavirenzgamma-Aminobutyric AcidGlutamic AcidGlutamineGlutathioneHIV Integrase InhibitorsReceptors, Tumor Necrosis Factor, Type I

Identifiers

PMID31045650
PMCPMC6625862
OpenAlexW2942520047

What OpenQuestion holds

Textmetadata
LicenceTDM
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.