2023
Self-Reported Neuropsychiatric Post–COVID-19 Condition and CSF Markers of Neuroinflammation
Farhadian S, Reisert H, McAlpine L, Chiarella J, Kosana P, Yoon J, Spudich S. Self-Reported Neuropsychiatric Post–COVID-19 Condition and CSF Markers of Neuroinflammation. JAMA Network Open 2023, 6: e2342741. PMID: 37948085, PMCID: PMC10638645, DOI: 10.1001/jamanetworkopen.2023.42741.Peer-Reviewed Original ResearchBrain volumetrics differ by Fiebig stage in acute HIV infection
Bolzenius J, Sacdalan C, Ndhlovu L, Sailasuta N, Trautmann L, Tipsuk S, Crowell T, Suttichom D, Colby D, Phanuphak N, Chan P, Premeaux T, Kroon E, Vasan S, Hsu D, Valcour V, Ananworanich J, Robb M, Ake J, Pohl K, Sriplienchan S, Spudich S, Paul R. Brain volumetrics differ by Fiebig stage in acute HIV infection. AIDS 2023, 37: 861-869. PMID: 36723491, PMCID: PMC10079583, DOI: 10.1097/qad.0000000000003496.Peer-Reviewed Original ResearchConceptsAcute HIV infectionNucleus accumbensFiebig stagesAcute infectionHIV infectionCaudate nucleusBrain volumeLower regional brain volumesAntiretroviral therapy initiationMarkers of neuroinflammationBrain volume alterationsCross-sectional studyRegional brain volumesT1-weighted scansTherapy initiationChronic infectionBrain volumetricsBrain disruptionThai malesViral factorsPutamenVolume alterationsAccumbensInfectionStimulant use
2022
Neuropathogenesis of HIV-1: insights from across the spectrum of acute through long-term treated infection
Killingsworth L, Spudich S. Neuropathogenesis of HIV-1: insights from across the spectrum of acute through long-term treated infection. Seminars In Immunopathology 2022, 44: 709-724. PMID: 35882661, PMCID: PMC10126949, DOI: 10.1007/s00281-022-00953-5.Peer-Reviewed Original ResearchConceptsCentral nervous systemHIV infectionInflammatory responseHIV entryChronic HIV infectionAcute HIV infectionNeuropathogenesis of HIVEarly inflammatory responsePathological inflammatory responsesOngoing neuropathologyAntiretroviral therapyViral suppressionNeurologic healthViral reservoirChronic infectionImmune mechanismsT lymphocytesHIV-1Viral infectionNervous systemInfectionHIVPathological consequencesBrainNeuropathogenesisNervous system consequences of COVID-19
Spudich S, Nath A. Nervous system consequences of COVID-19. Science 2022, 375: 267-269. PMID: 35050660, DOI: 10.1126/science.abm2052.Peer-Reviewed Original Research
2020
Cognitive disorders in people living with HIV
Winston A, Spudich S. Cognitive disorders in people living with HIV. The Lancet HIV 2020, 7: e504-e513. PMID: 32621876, DOI: 10.1016/s2352-3018(20)30107-7.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsCognitive disordersHIV reservoirConcomitant medication useLatent HIV reservoirCohort of peopleSuch cognitive disordersHigh rateMedication useExact prevalenceHIVCognitive functionBrain compartmentsDisordersOverall wellbeingSuch interventionsInterventionReduced ratesComorbiditiesCohortPrevalenceImpairmentRegional brain volumetric changes despite 2 years of treatment initiated during acute HIV infection.
Kallianpur KJ, Jahanshad N, Sailasuta N, Benjapornpong K, Chan P, Pothisri M, Dumrongpisutikul N, Laws E, Ndhlovu LC, Clifford KM, Paul R, Jagodzinski L, Krebs S, Ananworanich J, Spudich S, Valcour V. Regional brain volumetric changes despite 2 years of treatment initiated during acute HIV infection. AIDS 2020, 34: 415-426. PMID: 31725432, PMCID: PMC6994348, DOI: 10.1097/qad.0000000000002436.Peer-Reviewed Original ResearchConceptsCombination antiretroviral therapyRegional brain volumesBrain volumeSuppressive combination antiretroviral therapyBrain magnetic resonance imagingBrain volumetric changesAcute HIV infectionLongitudinal pipelineProspective cohort studyBrain metabolite levelsCerebrospinal fluid biomarkersVolumetric decreaseYears of treatmentMagnetic resonance imagingFreeSurfer longitudinal pipelineVoxel-wise analysisHigh baseline frequencyVolumes of putamenCART initiationHIV-1infectionProgressive HIVSimilar HIVAntiretroviral therapyCohort studyHIV exposureResting-state neural signatures of depressive symptoms in acute HIV
Philippi CL, Reyna L, Nedderman L, Chan P, Samboju V, Chang K, Phanuphak N, Ratnaratorn N, Hellmuth J, Benjapornpong K, Dumrongpisutikul N, Pothisri M, Robb ML, Ananworanich J, Spudich S, Valcour V, Paul R. Resting-state neural signatures of depressive symptoms in acute HIV. Journal Of NeuroVirology 2020, 26: 226-240. PMID: 31989446, PMCID: PMC7261250, DOI: 10.1007/s13365-020-00826-3.Peer-Reviewed Original ResearchConceptsResting-state functional connectivityAcute HIV infectionAnterior cingulate cortexDecreased resting-state functional connectivityDepressive symptomsAltered resting-state functional connectivityCombination antiretroviral therapyPersistent depressive symptomsUninfected control groupAmygdala seed regionPosterior cingulate/precuneusSymptoms of depressionVoxelwise regression analysesEmotion-related brain regionsAcute HIVChronic HIVThai HIVAntiretroviral therapyHIV RNASeed regionHIV infectionBlood biomarkersAHI groupLateral parietal regionsUninfected controls
2019
HIV persistence in the central nervous system during antiretroviral therapy: evidence and implications.
Spudich S, Clements JE. HIV persistence in the central nervous system during antiretroviral therapy: evidence and implications. AIDS 2019, 33 Suppl 2: s103-s106. PMID: 31789813, DOI: 10.1097/qad.0000000000002439.Peer-Reviewed Original ResearchNeurosyphilis During Acute HIV Infection: A CNS Immunologic and Virologic Characterization.
Chan P, Dumrongpisutikul N, Subra C, Colby DJ, Kroon E, Fletcher J, Sacdalan C, Phanuphak N, Valcour V, Ananworanich J, Trautmann L, Spudich S. Neurosyphilis During Acute HIV Infection: A CNS Immunologic and Virologic Characterization. JAIDS Journal Of Acquired Immune Deficiency Syndromes 2019, 82: e34-e37. PMID: 31180994, PMCID: PMC10126948, DOI: 10.1097/qai.0000000000002114.Peer-Reviewed Original ResearchSlowly progressive fatal PML-IRIS following antiretroviral initiation at CD4+ nadir of 350 cells/mm3 despite CD4+ cell count rise to 900 cells/mm3
Sandhu MR, Rutledge R, Grant M, Mahajan A, Spudich S. Slowly progressive fatal PML-IRIS following antiretroviral initiation at CD4+ nadir of 350 cells/mm3 despite CD4+ cell count rise to 900 cells/mm3. International Journal Of STD & AIDS 2019, 30: 810-813. PMID: 31046614, DOI: 10.1177/0956462419835966.Peer-Reviewed Case Reports and Technical NotesMeSH KeywordsAdultAIDS-Related Opportunistic InfectionsAntiretroviral Therapy, Highly ActiveBrainCD4 Lymphocyte CountDisease ProgressionDystonic DisordersFatal OutcomeHIV InfectionsHumansImmune Reconstitution Inflammatory SyndromeJC VirusLeukoencephalopathy, Progressive MultifocalMagnetic Resonance ImagingMaleTreatment OutcomeConceptsImmune reconstitution inflammatory syndromePML-IRISAntiretroviral therapyCell countInflammatory syndromeInitiation of ARTHIV/AIDS patientsReconstitution inflammatory syndromeRobust immune reconstitutionCells/mm3Progressive multifocal leukoencephalopathyRole of CD4Blood-brain barrierCells/Antiretroviral initiationInflammatory picturePersistent positivityImmune reconstitutionMultifocal leukoencephalopathyNeurological symptomsOpportunistic infectionsAIDS patientsVirus antigenImmune responseJC virusPredicting Efavirenz Concentrations in the Brain Tissue of HIV‐Infected Individuals and Exploring their Relationship to Neurocognitive Impairment
Srinivas N, Joseph SB, Robertson K, Kincer LP, Menezes P, Adamson L, Schauer AP, Blake KH, White N, Sykes C, Luciw P, Eron JJ, Forrest A, Price R, Spudich S, Swanstrom R, Kashuba A. Predicting Efavirenz Concentrations in the Brain Tissue of HIV‐Infected Individuals and Exploring their Relationship to Neurocognitive Impairment. Clinical And Translational Science 2019, 12: 302-311. PMID: 30675981, PMCID: PMC6510381, DOI: 10.1111/cts.12620.Peer-Reviewed Original ResearchConceptsBrain tissue concentrationsCerebrospinal fluidBrain tissueRhesus macaquesNeurocognitive scoresPK/pharmacodynamic analysesPenetration of antiretroviralsTissue concentrationsExposure-response analysisConcentration-time curveAdult rhesus macaquesCSF AUCEfavirenz concentrationsPlasma AUCPharmacodynamic analysisClinical studiesTissue AUCNeurocognitive impairmentCSF samplesPharmacokinetic dataPK modelingHIVTime pointsAUCNecropsy
2018
Structural and functional brain imaging in acute HIV
Samboju V, Philippi CL, Chan P, Cobigo Y, Fletcher JLK, Robb M, Hellmuth J, Benjapornpong K, Dumrongpisutikul N, Pothisri M, Paul R, Ananworanich J, Spudich S, Valcour V, 010/RV254 S, teams R. Structural and functional brain imaging in acute HIV. NeuroImage Clinical 2018, 20: 327-335. PMID: 30101063, PMCID: PMC6082997, DOI: 10.1016/j.nicl.2018.07.024.Peer-Reviewed Original ResearchConceptsResting-state functional connectivityAcute HIV infectionAntiretroviral treatmentDiffusion tensor imagingAHI groupNPZ-4HIV RNARadial diffusivityFractional anisotropyCerebrospinal fluidHigher CD4 cell countsParahippocampal cortexHigher resting-state functional connectivityCombination antiretroviral treatmentHIV disease variablesLeft parahippocampal cortexMean CD4 countPlasma HIV RNACD4 cell countCopies/mLNeuropsychological testing performanceMicrostructural white matterFunctional brain integrityMiddle frontal gyrusSuperior longitudinal fasciculusCentral Nervous System Inflammation and Infection during Early, Nonaccelerated Simian-Human Immunodeficiency Virus Infection in Rhesus Macaques
Hsu DC, Sunyakumthorn P, Wegner M, Schuetz A, Silsorn D, Estes JD, Deleage C, Tomusange K, Lakhashe SK, Ruprecht RM, Lombardini E, Im-Erbsin R, Kuncharin Y, Phuang-Ngern Y, Inthawong D, Chuenarom W, Burke R, Robb ML, Ndhlovu LC, Ananworanich J, Valcour V, O'Connell RJ, Spudich S, Michael NL, Vasan S. Central Nervous System Inflammation and Infection during Early, Nonaccelerated Simian-Human Immunodeficiency Virus Infection in Rhesus Macaques. Journal Of Virology 2018, 92: 10.1128/jvi.00222-18. PMID: 29563297, PMCID: PMC5952152, DOI: 10.1128/jvi.00222-18.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigens, CDAntigens, Differentiation, MyelomonocyticBrainCD4 Lymphocyte CountCD4-Positive T-LymphocytesCells, CulturedDisease Models, AnimalHIV-1HumansMacaca mulattaMacrophagesMeningesMicrogliaMonocytesParenchymal TissueReceptors, Cell SurfaceRNA, ViralSimian Acquired Immunodeficiency SyndromeSimian immunodeficiency virusViral LoadConceptsSimian-human immunodeficiency virusSimian immunodeficiency virusCD68/CD163Immunodeficiency virus infectionCentral nervous systemBrain parenchymaHIV envelopeImmunodeficiency virusVirus infectionEarly human immunodeficiency virus (HIV) infectionSimian-human immunodeficiency virus (SHIV) infectionCentral nervous system inflammationHuman immunodeficiency virus (HIV) infectionCentral nervous system involvementPathogenic simian immunodeficiency virusRhesus macaquesT-cell-mediated processEarly clinical courseSHIV-infected animalsNervous system inflammationT-cell countsCell-mediated inflammationNervous system involvementEnd-stage diseaseHIV cure strategiesLongitudinal Trajectories of Brain Volume and Cortical Thickness in Treated and Untreated Primary Human Immunodeficiency Virus Infection
Sanford R, Ances BM, Meyerhoff DJ, Price RW, Fuchs D, Zetterberg H, Spudich S, Collins DL. Longitudinal Trajectories of Brain Volume and Cortical Thickness in Treated and Untreated Primary Human Immunodeficiency Virus Infection. Clinical Infectious Diseases 2018, 67: 1697-1704. PMID: 29697762, PMCID: PMC6233681, DOI: 10.1093/cid/ciy362.Peer-Reviewed Original ResearchConceptsCombination antiretroviral therapyHuman immunodeficiency virusPrimary HIV infectionChronic HIV infectionCortical thicknessHIV infectionCortical thinningUntreated infectionTemporal lobeBrain volumeImpact of HIVPrimary human immunodeficiency virus (HIV) infectionEarly combination antiretroviral therapyUntreated human immunodeficiency virusHuman immunodeficiency virus (HIV) infectionLongitudinal magnetic resonance imagingImmunodeficiency virus infectionCerebrospinal fluid biomarkersStructural brain changesCortical gray matterMagnetic resonance imagingBrain morphometric measuresCART durationAntiretroviral therapySubcortical atrophy
2016
Neurologic signs and symptoms frequently manifest in acute HIV infection
Hellmuth J, Fletcher JL, Valcour V, Kroon E, Ananworanich J, Intasan J, Lerdlum S, Narvid J, Pothisri M, Allen I, Krebs SJ, Slike B, Prueksakaew P, Jagodzinski LL, Puttamaswin S, Phanuphak N, Spudich S, Phanuphak P, Phanuphak N, Colby D, Chalermchai T, Chomchey N, Suttichom D, Rattanamanee S, Sangtawan P, Rattanamanee S, Nuntapinit B, Rakyat P, Inprakong S, Lucksanawong S, Ruangjan P, Nuchwong A, Kruacharoen P, O’Connell R, Adams C, Clifford K, Wendelken L, Le L, Mistry H, Tovanabutra S, Pinyakorn S, Robb M, Paul R. Neurologic signs and symptoms frequently manifest in acute HIV infection. Neurology 2016, 87: 148-154. PMID: 27287217, PMCID: PMC4940060, DOI: 10.1212/wnl.0000000000002837.Peer-Reviewed Original ResearchConceptsCombination antiretroviral therapyAcute HIV infectionNeurologic findingsHIV infectionAcute HIVNeurologic manifestationsNeurologic evaluationHIV infection durationLog10 HIV RNASevere neurologic manifestationsStructural neuroimaging abnormalitiesCART initiationAntiretroviral therapyHIV RNAInflammatory markersMotor findingsNeuroimaging abnormalitiesStudy entryNeurologic signsBrain MRIInfection durationCognitive symptomsViral factorsInfectionDiagnosisCROI 2016: Neurologic Complications of HIV Infection.
Spudich SS, Ances BM. CROI 2016: Neurologic Complications of HIV Infection. Topics In Antiviral Medicine 2016, 24: 29-37. PMID: 27398860, PMCID: PMC6148921.Peer-Reviewed Original ResearchConceptsCentral nervous systemHIV infectionTraditional vascular risk factorsPrognosis of handSuppressive antiretroviral treatmentVascular risk factorsStandard antiretroviral therapyPotential adjunctive therapyLarge epidemiologic studiesMacrophage lineage cellsRecreational drug useHIV escapeHIV measuresAntiretroviral therapyHepatic dysfunctionNeurologic complicationsAdjunctive therapyAntiretroviral treatmentSystemic compartmentOpportunistic infectionsHIV replicationFemale sexPotential complicationsRisk factorsNeurocognitive disorders
2012
Change in Brain Magnetic Resonance Spectroscopy after Treatment during Acute HIV Infection
Sailasuta N, Ross W, Ananworanich J, Chalermchai T, DeGruttola V, Lerdlum S, Pothisri M, Busovaca E, Ratto-Kim S, Jagodzinski L, Spudich S, Michael N, Kim JH, Valcour V, Phanuphak N, Teeratakulpisarn N, Fletcher J, Suttichom D, Pinyakorn S, Rattanamanee S, Chomchey N, Mangum P, Ubolyam S, Suwanwela N, Chaisinanunkul N, Suthiponpaisan U, Sutthapas C, deSouza M, Ngauy V, Trichavaroj R, Akapirat S, Marovich M, Wendelken L, Busovaca E, Liu C, Mun E, Miller B. Change in Brain Magnetic Resonance Spectroscopy after Treatment during Acute HIV Infection. PLOS ONE 2012, 7: e49272. PMID: 23229129, PMCID: PMC3500278, DOI: 10.1371/journal.pone.0049272.Peer-Reviewed Original ResearchConceptsOccipital gray matterAntiretroviral therapyHIV infectionFrontal gray matterFrontal white matterN-acetyl aspartateBasal gangliaControl subjectsGray matterHIV-negative control subjectsInitiation of ARTSingle-voxel proton magnetic resonance spectroscopyBrain magnetic resonance spectroscopyAcute HIV infectionEarly antiretroviral therapyBrain metabolite levelsNegative control subjectsProton magnetic resonance spectroscopyMagnetic resonance spectroscopyHIV subjectsBrain inflammationNeuronal injuryHIV casesCNS injuryCellular inflammation