2023
CD4dimCD8bright T cells are inversely associated with neuro-inflammatory markers among people with HIV
Albalawi Y, Shull T, Virdi A, Subra C, Mitchell J, Slike B, Jian N, Krebs S, Sacdalan C, Ratnaratorn N, Hsu D, Phanuphak N, Spudich S, Trautmann L, Al-Harthi L. CD4dimCD8bright T cells are inversely associated with neuro-inflammatory markers among people with HIV. AIDS 2023, 38: 1-7. PMID: 37792358, PMCID: PMC10715695, DOI: 10.1097/qad.0000000000003743.Peer-Reviewed Original ResearchConceptsCombination antiretroviral therapyT cellsWeeks 0CD4-CD8Cerebrospinal fluidImmune activationSoluble markersSuppressive combination antiretroviral therapyPeripheral blood T cellsNeuro-inflammatory markersSubset of CD8Anti-inflammatory propertiesBlood T cellsConfidence intervalsPlasma of peopleT-cell typeCART initiationCSF neopterinPlasma RANTESAntiretroviral therapyWeek 24IP-10IL-6Lumbar punctureIL-8
2020
Regional 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
Exosomal MicroRNAs Associate With Neuropsychological Performance in Individuals With HIV Infection on Antiretroviral Therapy.
OʼMeara T, Kong Y, Chiarella J, Price RW, Chaudhury R, Liu X, Spudich S, Robertson K, Emu B, Lu L. Exosomal MicroRNAs Associate With Neuropsychological Performance in Individuals With HIV Infection on Antiretroviral Therapy. JAIDS Journal Of Acquired Immune Deficiency Syndromes 2019, 82: 514-522. PMID: 31714431, PMCID: PMC6857839, DOI: 10.1097/qai.0000000000002187.Peer-Reviewed Original ResearchConceptsCombination antiretroviral therapyNeuropsychological performanceAntiretroviral therapyViral suppressionHIV infectionNeurocognitive dysfunctionExo-miRNAsEarly infection groupCentral nervous systemSystemic viral suppressionTyrosine receptor kinaseInfection groupChronic infectionPLWHCross-sectional examinationNervous systemEarly infectionNeuropsychological scoresInfectionConsistent findingNeuropsychological batteryHIVNeurodegeneration pathwaysDysfunctionTherapy
2018
Longitudinal 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 atrophyGlobal Health Neurology: HIV/AIDS
Patel PB, Spudich SS. Global Health Neurology: HIV/AIDS. Seminars In Neurology 2018, 38: 238-246. PMID: 29791950, DOI: 10.1055/s-0038-1649334.Peer-Reviewed Original ResearchConceptsNeurologic complicationsLong-term HIVCombination antiretroviral therapyImpact of HIVResource-limited settingsHIV/AIDSAntiretroviral therapyOpportunistic infectionsCerebrovascular diseaseNeurocognitive disordersHIVMortality rateMajority of studiesComplicationsInternational studiesTherapyInfectionPrevalenceAIDSDiseaseIndividualsSafety of lumbar puncture procedure in an international research setting during acute HIV infection
Chan P, Hellmuth J, Colby D, Kroon E, Sacdalan C, Fletcher J, Patel P, Pinyakorn S, Valcour V, Ananworanich J, Spudich S. Safety of lumbar puncture procedure in an international research setting during acute HIV infection. Journal Of Virus Eradication 2018, 4: 16-20. PMID: 29568548, PMCID: PMC5851179, DOI: 10.1016/s2055-6640(20)30236-3.Peer-Reviewed Original ResearchPost-lumbar puncture headacheAcute HIV infectionCombination antiretroviral therapyBody mass indexLumbar punctureHIV infectionAtraumatic needlesCerebrospinal fluidCSF HIV viral loadHigher body mass indexT-lymphocyte countsAcute retroviral syndromeHIV viral loadFrequency of PPHCerebrospinal fluid volumeLumbar puncture procedureCART initiationAntiretroviral therapyLymphocyte countMass indexViral loadPuncture headacheClinical recordsLongitudinal visitsSubgroup analysis
2017
Neurological Complications of HIV Infection
Farhadian S, Patel P, Spudich S. Neurological Complications of HIV Infection. Current Infectious Disease Reports 2017, 19: 50. PMID: 29164407, PMCID: PMC7456329, DOI: 10.1007/s11908-017-0606-5.BooksCombination antiretroviral therapyHIV infectionSuppressive combination antiretroviral therapyChronic HIV infectionPathogenesis of HANDPurpose of ReviewHIVHIV-associated dementiaNeurofilament light chainAntiretroviral therapyCNS infectionNeurological complicationsNeurological outcomeHIV diseaseAsymptomatic individualsMonocyte activityBody of evidenceNeurocognitive disordersPreventive strategiesMultifactorial causesCellular injuryMild formInfectionHIVLight chainRecent studiesDepression and Anxiety are Common in Acute HIV Infection and Associate with Plasma Immune Activation
Hellmuth J, Colby D, Valcour V, Suttichom D, Spudich S, Ananworanich J, Prueksakaew P, Sailasuta N, Allen I, Jagodzinski LL, Slike B, Ochi D, Paul R, on behalf of the RV254/SEARCH 010 Study Group. Depression and Anxiety are Common in Acute HIV Infection and Associate with Plasma Immune Activation. AIDS And Behavior 2017, 21: 3238-3246. PMID: 28484888, PMCID: PMC5830305, DOI: 10.1007/s10461-017-1788-4.Peer-Reviewed Original ResearchConceptsAcute HIV infectionCombination antiretroviral therapyPlasma HIV RNAHIV infectionImmune activationCD4 countHIV RNAPlasma neopterinStudy entryBaseline plasma HIV RNALow CD4 countRelevant depressive symptomsAnxiety symptomsCerebrospinal fluid measuresAssessment of depressionAHI participantsAntiretroviral therapyBlood markersObservational studyDepressive symptomsMacrophage activationAffective symptomsPossible associationSymptomsFluid measuresHigh Number of Activated CD8+ T Cells Targeting HIV Antigens Are Present in Cerebrospinal Fluid in Acute HIV Infection
Kessing CF, Spudich S, Valcour V, Cartwright P, Chalermchai T, Fletcher JL, Takata H, Nichols C, Josey B, Slike B, Krebs S, Sailsuta N, Lerdlum S, Jagodzinski L, Tipsuk S, Suttichom D, Rattanamanee S, Zetterberg H, Hellmuth J, Phanuphak N, Robb M, Michael N, Ananworanich J, Trautmann L. High Number of Activated CD8+ T Cells Targeting HIV Antigens Are Present in Cerebrospinal Fluid in Acute HIV Infection. JAIDS Journal Of Acquired Immune Deficiency Syndromes 2017, 75: 108-117. PMID: 28177966, PMCID: PMC5388590, DOI: 10.1097/qai.0000000000001301.Peer-Reviewed Original ResearchConceptsAcute HIV infectionCD8 T cellsChronic HIV infectionHIV infectionT cellsCerebrospinal fluidCD8 T cell effector functionsHIV-specific CD8 T cellsCentral nervous system infiltrationT cell effector functionT cell receptor repertoireCSF HIV RNACombination antiretroviral therapyTCR Vbeta repertoireCell effector functionsCell receptor repertoireHIV specificitiesAntiretroviral therapyCNS inflammationHIV RNAVbeta repertoireMicroglial activationActivated CD8HIV antigenHIV epitopesBlood-Brain Barrier Disruption Is Initiated During Primary HIV Infection and Not Rapidly Altered by Antiretroviral Therapy
Rahimy E, Li FY, Hagberg L, Fuchs D, Robertson K, Meyerhoff DJ, Zetterberg H, Price RW, Gisslén M, Spudich S. Blood-Brain Barrier Disruption Is Initiated During Primary HIV Infection and Not Rapidly Altered by Antiretroviral Therapy. The Journal Of Infectious Diseases 2017, 215: 1132-1140. PMID: 28368497, PMCID: PMC5426376, DOI: 10.1093/infdis/jix013.Peer-Reviewed Original ResearchConceptsPrimary HIV infectionCombination antiretroviral therapyHIV infectionNeurofilament light chainAntiretroviral therapyCreatinine levelsCerebrospinal fluidN-acetylaspartateAbnormal blood-brain barrier (BBB) permeabilityPrimary human immunodeficiency virus (HIV) infectionBlood-brain barrier disruptionHuman immunodeficiency virus (HIV) infectionBlood-brain barrier permeabilityNeuropsychological performanceImmunodeficiency virus infectionParietal gray matterYears of treatmentLongitudinal observational studyCART durationCART initiationMedian intervalNeuronal injuryAlbumin quotientNfL levelsCSF levelsImmediate initiation of cART is associated with lower levels of cerebrospinal fluid YKL-40, a marker of microglial activation, in HIV-1 infection
Peluso MJ, Valcour V, Phanuphak N, Ananworanich J, Fletcher JL, Chalermchai T, Krebs SJ, Robb ML, Hellmuth J, Gisslén M, Zetterberg H, Spudich S. Immediate initiation of cART is associated with lower levels of cerebrospinal fluid YKL-40, a marker of microglial activation, in HIV-1 infection. AIDS 2017, 31: 247-252. PMID: 27819802, PMCID: PMC5844231, DOI: 10.1097/qad.0000000000001314.Peer-Reviewed Original ResearchConceptsChronic HIV-1 infectionCombination antiretroviral therapyCerebrospinal fluid (CSF) YKL-40Group of HIVHIV-1 infectionYKL-40Treatment initiationUntreated chronic HIV-1 infectionMedian YKL-40Early HIV infectionCSF YKL-40Chemokine ligand 10Neurofilament light chainCross-sectional studyMann-Whitney testAntiretroviral therapyHIV neuropathogenesisMicroglial activationHIV infectionPrognostic valueChi groupMicroglial cellsAHI groupImmediate initiationBlood sampling
2016
HIV-Associated Neurologic Disorders and Central Nervous System Opportunistic Infections in HIV
Le LT, Spudich SS. HIV-Associated Neurologic Disorders and Central Nervous System Opportunistic Infections in HIV. Seminars In Neurology 2016, 36: 373-381. PMID: 27643907, DOI: 10.1055/s-0036-1585454.Peer-Reviewed Original ResearchConceptsCombination antiretroviral therapyAsymptomatic neurocognitive impairmentPlasma viral loadViral loadMild neurocognitive disorderCerebral toxoplasmosisCryptococcal meningitisOpportunistic infectionsNeurocognitive disordersCentral nervous system opportunistic infectionsCNS immune reconstitution inflammatory syndromeDetectable plasma viral loadImmune reconstitution inflammatory syndromeCentral nervous system symptomsClassic opportunistic infectionsCSF viral loadProgressive neurologic symptomsReconstitution inflammatory syndromeT-cell countsProgressive multifocal leukoencephalopathyNervous system symptomsPresentation of infectionHigher mortality riskHigher CD4Immune recoveryNeurologic 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 factorsInfectionDiagnosisCognitive Impairment and Persistent CNS Injury in Treated HIV
Chan P, Hellmuth J, Spudich S, Valcour V. Cognitive Impairment and Persistent CNS Injury in Treated HIV. Current HIV/AIDS Reports 2016, 13: 209-217. PMID: 27188299, PMCID: PMC4977199, DOI: 10.1007/s11904-016-0319-7.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsCentral nervous systemCombination antiretroviral therapyCognitive impairmentPersistent immune activationPre-cART eraPlasma HIV RNACD8 encephalitisHIV biomarkersTreated HIVAntiretroviral therapyCNS involvementHIV RNAHIV infectionImaging findingsImmune activationCNS injuryHIV StudyChronic illnessNervous systemViral invasionCognitive outcomesCognitive manifestationsCognitive changesInfectionImpairmentImmune activation in the central nervous system throughout the course of HIV infection
Spudich SS. Immune activation in the central nervous system throughout the course of HIV infection. Current Opinion In HIV And AIDS 2016, 11: 226-233. PMID: 26760827, PMCID: PMC4773903, DOI: 10.1097/coh.0000000000000243.Peer-Reviewed Original ResearchConceptsCombination antiretroviral therapyImmune activationAntiretroviral therapySuppressive combination antiretroviral therapyLong-term neurologic sequelaeCentral nervous system responseCNS immune activationFeatures of homeostasisPersistent immune activationBrain microglial cellsCervical lymph nodesCentral nervous systemSustained immune responseNervous system responsesImmune surveillance networkNeurologic sequelaeAcute infectionHIV infectionLymph nodesActivation associatesMicroglial cellsChronic infectionCNS cellsImmune responseCerebrospinal fluid
2015
Neuropsychological Impairment in Acute HIV and the Effect of Immediate Antiretroviral Therapy
Kore I, Ananworanich J, Valcour V, Fletcher JL, Chalermchai T, Paul R, Reynolds J, Tipsuk S, Ubolyam S, Rattanamanee S, Jagodzinski L, Kim J, Spudich S. Neuropsychological Impairment in Acute HIV and the Effect of Immediate Antiretroviral Therapy. JAIDS Journal Of Acquired Immune Deficiency Syndromes 2015, 70: 393-399. PMID: 26509933, PMCID: PMC4625393, DOI: 10.1097/qai.0000000000000746.Peer-Reviewed Original ResearchConceptsCombination antiretroviral therapyCerebrospinal fluid HIV RNAEarly combination antiretroviral therapyAcute HIV infectionAHI participantsAntiretroviral therapyHIV RNANeurological Response to cART vs. cART plus Integrase Inhibitor and CCR5 Antagonist Initiated during Acute HIV
Valcour VG, Spudich SS, Sailasuta N, Phanuphak N, Lerdlum S, Fletcher JL, Kroon ED, Jagodzinski LL, Allen IE, Adams CL, Prueksakaew P, Slike BM, Hellmuth JM, Kim JH, Ananworanich J, . Neurological Response to cART vs. cART plus Integrase Inhibitor and CCR5 Antagonist Initiated during Acute HIV. PLOS ONE 2015, 10: e0142600. PMID: 26555069, PMCID: PMC4640512, DOI: 10.1371/journal.pone.0142600.Peer-Reviewed Original ResearchConceptsCombination antiretroviral therapyStandard combination antiretroviral therapyLog10 HIV RNAAcute HIVCSF cytokinesHIV RNACentral nervous system outcomesIntegrase inhibitorsGamma-induced protein 10Duration of HIVFiebig stages IAcute HIV infectionHIV RNA levelsCNS outcomesAntiretroviral therapyInflammatory markersWeek 24Antiretroviral treatmentHIV infectionPlasma neopterinRandomized armProspective evaluationMean ageHealthy controlsCCR5 antagonistsAbsence of Cerebrospinal Fluid Signs of Neuronal Injury Before and After Immediate Antiretroviral Therapy in Acute HIV Infection
Peluso MJ, Valcour V, Ananworanich J, Sithinamsuwan P, Chalermchai T, Fletcher JL, Lerdlum S, Chomchey N, Slike B, Sailasuta N, Gisslén M, Zetterberg H, Spudich S, Teams O. Absence of Cerebrospinal Fluid Signs of Neuronal Injury Before and After Immediate Antiretroviral Therapy in Acute HIV Infection. The Journal Of Infectious Diseases 2015, 212: 1759-1767. PMID: 25995196, PMCID: PMC4633761, DOI: 10.1093/infdis/jiv296.Peer-Reviewed Original ResearchConceptsCombination antiretroviral therapyAcute HIV infectionCSF NfL levelsNeurofilament light chainChronic HIV infectionHIV infectionNfL levelsParietal gray matterFrontal white matterNeuronal injuryAcute infectionGray matterCART initiationAntiretroviral therapyAcute human immunodeficiency virus (HIV) infectionCerebrospinal fluid neurofilament light chainProton magnetic resonance spectroscopic findingsWhite matterHuman immunodeficiency virus (HIV) infectionN-acetylaspartate/creatineMagnetic resonance spectroscopic findingsImmediate antiretroviral therapyImmunodeficiency virus infectionFrontal gray matterAxonal injuryNeuropathogenesis of HIV: From Initial Neuroinvasion to HIV-Associated Neurocognitive Disorder (HAND)
Zayyad Z, Spudich S. Neuropathogenesis of HIV: From Initial Neuroinvasion to HIV-Associated Neurocognitive Disorder (HAND). Current HIV/AIDS Reports 2015, 12: 16-24. PMID: 25604237, PMCID: PMC4741099, DOI: 10.1007/s11904-014-0255-3.Peer-Reviewed Original ResearchConceptsHIV-Associated Neurocognitive DisordersCentral nervous systemCombination antiretroviral therapyNeurocognitive disordersTissue reservoirsInitial viral entryTargets of infectionCourse of infectionEarly-stage infectionHIV eradicationAntiretroviral therapyHIV neuropathogenesisSevere immunosuppressionClinical symptomsHIV replicationHIV epidemicLocal infectionCNS cellsPathological involvementPathogenetic processSevere formNervous systemNeurological diseasesAdvanced stageHIV