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
2022
Correlation between CD4/CD8 ratio and neurocognitive performance during early HIV infection
Le LT, Price RW, Gisslén M, Zetterberg H, Emu B, Fabre R, Christian P, Andersen S, Spudich S, Vassallo M. Correlation between CD4/CD8 ratio and neurocognitive performance during early HIV infection. HIV Medicine 2022, 24: 442-452. PMID: 36134890, DOI: 10.1111/hiv.13411.Peer-Reviewed Original ResearchConceptsCD4/CD8 ratioPrimary HIV infectionCD8 ratioImmune activationHIV infectionNeuronal injuryAntiretroviral treatmentNeurocognitive performanceMean CD4/CD8 ratioCSF neurofilament light chainART-naïve participantsEarly HIV infectionCerebrospinal fluid markersNeurofilament light chainNeuropsychological testing performancePsychomotor speed performancePHI participantsStudy cohortCSF markersChronic infectionBrain injuryRetrospective analysisFluid markersInfectionInjuryHIV Disease Dynamics and Markers of Inflammation and CNS Injury During Primary HIV Infection and Their Relationship to Cognitive Performance
Longino AA, Paul R, Wang Y, Lama JR, Brandes P, Ruiz E, Correa C, Keating S, Spudich SS, Pilcher C, Vecchio A, Pasalar S, Ignacio R, Valdez R, Dasgupta S, Robertson K, Duerr A. HIV Disease Dynamics and Markers of Inflammation and CNS Injury During Primary HIV Infection and Their Relationship to Cognitive Performance. JAIDS Journal Of Acquired Immune Deficiency Syndromes 2022, 89: 183-190. PMID: 34629415, PMCID: PMC8752485, DOI: 10.1097/qai.0000000000002832.Peer-Reviewed Original ResearchConceptsAcute HIV infectionAntiretroviral therapyHIV infectionWeek 192CNS injuryCSF biomarkersNP scoresHigher pre-ART VLCognitive performanceChronic cognitive symptomsSustained antiretroviral therapyPrimary HIV infectionMarkers of inflammationCerebrospinal fluid biomarkersPsychosocial risk factorsART initiationCNS inflammationNeuronal injuryAcute infectionImmune activationFluid biomarkersRisk factorsHIV disease dynamicsInjury peaksCognitive symptoms
2021
Cerebrospinal fluid CD4+ T cell infection in humans and macaques during acute HIV-1 and SHIV infection
Sharma V, Creegan M, Tokarev A, Hsu D, Slike BM, Sacdalan C, Chan P, Spudich S, Ananworanich J, Eller MA, Krebs SJ, Vasan S, Bolton DL. Cerebrospinal fluid CD4+ T cell infection in humans and macaques during acute HIV-1 and SHIV infection. PLOS Pathogens 2021, 17: e1010105. PMID: 34874976, PMCID: PMC8683024, DOI: 10.1371/journal.ppat.1010105.Peer-Reviewed Original ResearchConceptsT-cell infectionCentral nervous systemAcute HIV-1HIV-1 replicationCerebrospinal fluidT cellsHIV-1Peripheral bloodViral reservoirCell infectionBroad immune activationCerebrospinal fluid CD4CNS viral reservoirCSF T cellsHIV-1 cureActive viral transcriptionLong-term inflammationViral RNACSF CD4Early neuroinflammationAntiretroviral therapyHuman cerebrospinal fluidAcute infectionImmune activationCNS compartment
2020
Selective Decay of Intact HIV-1 Proviral DNA on Antiretroviral Therapy
Gandhi R, Cyktor J, Bosch R, Mar H, Laird G, Martin A, Collier A, Riddler S, Macatangay B, Rinaldo C, Eron J, Siliciano J, McMahon D, Mellors J, Hogg E, LeBlanc R, Scello C, Palm D, Gandhi M, Fletcher C, Podany A, Aweeka F, Halvas L, Dragavon J, Joseph J, Lagattuta R, Lin L, Pederson S, Robertson K, Rubin L, Smith D, Spudich S, Tsibris A. Selective Decay of Intact HIV-1 Proviral DNA on Antiretroviral Therapy. The Journal Of Infectious Diseases 2020, 223: 225-233. PMID: 32823274, PMCID: PMC7857155, DOI: 10.1093/infdis/jiaa532.Peer-Reviewed Original ResearchConceptsTotal HIV-1 DNAResidual plasma viremiaAntiretroviral therapyHIV-1 DNAProvirus levelsPlasma viremiaLong-term antiretroviral therapyDefective HIV-1 provirusesHIV-1 proviral DNAReplication-competent reservoirSuppressive antiretroviral therapyMarkers of inflammationReplication-competent provirusesHIV-1 provirusART initiationImmune activationHIV-1Proviral DNATime pointsInfected cellsViremiaDefective provirusesInflammationTherapyProvirus
2019
Potential for early antiretroviral therapy to reduce central nervous system HIV-1 persistence.
Spudich S, Peterson J, Fuchs D, Price RW, Gisslen M. Potential for early antiretroviral therapy to reduce central nervous system HIV-1 persistence. AIDS 2019, 33 Suppl 2: s135-s144. PMID: 31789814, DOI: 10.1097/qad.0000000000002326.Peer-Reviewed Original ResearchConceptsHIV-1 infectionCentral nervous systemEarly antiretroviral therapyAntiretroviral therapyHIV-1 persistenceEarly treatmentInitiation of ARTCentral nervous inflammationEarly-treatment cohortHIV-1 exposureHIV-1 reservoirCourse of infectionClinical neurological diseaseCNS infectionHIV reservoirTreatment cohortsImmune activationCNS compartmentViral controlHIV-1Cerebrospinal fluidClinical reportsNervous systemEarly infectionNeurological diseasesMarkers of CNS Injury in Adults Living With HIV With CSF HIV Not Detected vs Detected <20 Copies/mL
Farhadian SF, Mistry H, Kirchwey T, Chiarella J, Calvi R, Chintanaphol M, Patel P, Landry ML, Robertson K, Spudich SS. Markers of CNS Injury in Adults Living With HIV With CSF HIV Not Detected vs Detected <20 Copies/mL. Open Forum Infectious Diseases 2019, 6: ofz528. PMID: 31893212, PMCID: PMC6934883, DOI: 10.1093/ofid/ofz528.Peer-Reviewed Original ResearchAntiretroviral therapyHIV RNACerebrospinal fluidBlood-brain barrier integrityCentral nervous system pathologyCNS immune activationCSF HIV RNANervous system pathologyCSF HIVCSF RNAImmune activationCNS injuryCopies/Neuropsychological testingSystem pathologyBarrier integrityCNS parametersHIVStandard assayExecutive functionRNAInjuryTherapySignificance of RNAPathologyVery Early Initiation of Antiretroviral Therapy During Acute HIV Infection Is Associated With Normalized Levels of Immune Activation Markers in Cerebrospinal Fluid but Not in Plasma
Hellmuth J, Slike BM, Sacdalan C, Best J, Kroon E, Phanuphak N, Fletcher JLK, Prueksakaew P, Jagodzinski LL, Valcour V, Robb M, Ananworanich J, Allen IE, Krebs SJ, Spudich S. Very Early Initiation of Antiretroviral Therapy During Acute HIV Infection Is Associated With Normalized Levels of Immune Activation Markers in Cerebrospinal Fluid but Not in Plasma. The Journal Of Infectious Diseases 2019, 220: 1885-1891. PMID: 30668739, PMCID: PMC6833977, DOI: 10.1093/infdis/jiz030.Peer-Reviewed Original ResearchConceptsAcute HIV infectionAntiretroviral therapyART initiationCerebrospinal fluidWeek 96Week 24HIV infectionImmune activationAHI groupHuman immunodeficiency virus (HIV) infectionEarly ART initiationPlasma CCL2 levelsTrajectory of HIVChronic immune activationImmune activation markersSuppressive antiretroviral therapyImmunodeficiency virus infectionInterleukin-6 levelsMarkers of inflammationPlasma neopterin levelsWeeks of treatmentCentral nervous systemART regimenCCL2 levelsNeopterin levels
2018
Single-cell RNA sequencing reveals microglia-like cells in cerebrospinal fluid during virologically suppressed HIV
Farhadian SF, Mehta SS, Zografou C, Robertson K, Price RW, Pappalardo J, Chiarella J, Hafler DA, Spudich SS. Single-cell RNA sequencing reveals microglia-like cells in cerebrospinal fluid during virologically suppressed HIV. JCI Insight 2018, 3: e121718. PMID: 30232286, PMCID: PMC6237230, DOI: 10.1172/jci.insight.121718.Peer-Reviewed Original ResearchConceptsCerebrospinal fluidHIV infectionImmune activationAntiretroviral therapyNeuronal injuryCentral nervous system immune activationLong-term suppressive antiretroviral therapySingle-cell RNA sequencingCNS immune activationDisease-associated microgliaSuppressive antiretroviral therapyImmune cell subsetsMicroglia-like cellsGene expression signaturesNeuronal damageNeuroinflammatory diseasesRNA sequencingCell subsetsCNS cellsNeurological conditionsRare subsetNeurocognitive impairmentMyeloid cellsCellular subsetsInfectionBrief Report
Chintanaphol M, Sacdalan C, Chottanapund S, Pinyakorn S, Buranapraditkun S, Crowell TA, Kroon E, Manasnayakorn S, Chipman JG, Schacker TW, Michael N, Phanuphak N, Spudich SS, Colby DJ, Ananworanich J. Brief Report. JAIDS Journal Of Acquired Immune Deficiency Syndromes 2018, 79: 244-248. PMID: 30212436, PMCID: PMC6143219, DOI: 10.1097/qai.0000000000001780.Peer-Reviewed Original ResearchConceptsAcute HIV infectionAdverse eventsLN biopsyAE incidenceBiopsy-related adverse eventsInguinal lymph node biopsyProcedure-related adverse eventsLatent HIV reservoirLymph node biopsyIncidence rate ratiosInstitutional review boardAHI participantsAIDS guidelinesAntiretroviral therapyHIV reservoirNode biopsyBaseline visitHIV infectionHIV pathogenesisMedian ageHIV characteristicsImmune activationLymphoid tissueThai menNIH Division
2017
Acute Retroviral Syndrome Is Associated With High Viral Burden, CD4 Depletion, and Immune Activation in Systemic and Tissue Compartments
Crowell TA, Colby DJ, Pinyakorn S, Fletcher JLK, Kroon E, Schuetz A, Krebs SJ, Slike BM, Leyre L, Chomont N, Jagodzinski LL, Sereti I, Utay NS, Dewar R, Rerknimitr R, Chomchey N, Trichavaroj R, Valcour VG, Spudich S, Michael NL, Robb ML, Phanuphak N, Ananworanich J, Teeratakulpisarn N, Sacdalan C, Sutthichom D, Rattanamanee S, Prueksakaew P, Ubolyam S, Eamyoung P, Puttamaswin S, Tipsuk S, Karnsomlap P, Ridtitid W, Connell R, Akapirat S, Phuang-Ngern Y, Sukhumvittaya S, Sajjaweerawan C, Jongrakthaitae S, Saetun P, Tragonlugsana N, Nuntapinit B, Tantibul N, Savadsuk H, Tovanabutr S. Acute Retroviral Syndrome Is Associated With High Viral Burden, CD4 Depletion, and Immune Activation in Systemic and Tissue Compartments. Clinical Infectious Diseases 2017, 66: 1540-1549. PMID: 29228130, PMCID: PMC5930255, DOI: 10.1093/cid/cix1063.Peer-Reviewed Original ResearchConceptsHigh viral burdenAcute retroviral syndromeAntiretroviral therapyCD4 depletionViral burdenImmune activationAdverse long-term clinical outcomesVoluntary human immunodeficiency virus (HIV) testingPlasma tumor necrosis factor alphaWeeks of ARTHuman immunodeficiency virus (HIV) testingLong-term clinical outcomesTumor necrosis factor alphaHigher HIV RNATotal HIV DNASuppressive antiretroviral therapyC-reactive proteinSigns/symptomsNecrosis factor alphaUnderwent lumbar punctureMultiple body compartmentsARS diagnosisFiebig stagesSigmoid biopsiesHIV RNADepression 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 measures
2016
Cognitive 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
2014
Progressive increase in central nervous system immune activation in untreated primary HIV-1 infection
Suh J, Sinclair E, Peterson J, Lee E, Kyriakides TC, Li FY, Hagberg L, Fuchs D, Price RW, Gisslen M, Spudich S. Progressive increase in central nervous system immune activation in untreated primary HIV-1 infection. Journal Of Neuroinflammation 2014, 11: 199. PMID: 25465205, PMCID: PMC4263211, DOI: 10.1186/s12974-014-0199-y.Peer-Reviewed Original ResearchConceptsPrimary HIV-1 infectionHIV-1 infectionCSF neopterinCerebrospinal fluidT cellsHIV infectionCentral nervous system immune activationUntreated primary HIV-1 infectionBaseline levelsEarly HIV-1 infectionCSF neopterin concentrationsNervous system inflammationMixed effects modelsCluster of differentiationMajority of subjectsCNS inflammationSystem inflammationAverage followNeopterin concentrationsHIV transmissionImmune activationLumbar punctureResultsA totalIntrathecal inflammationNatural courseCROI 2014: Neurologic complications of HIV infection.
Spudich SS. CROI 2014: Neurologic complications of HIV infection. Topics In Antiviral Medicine 2014, 22: 594-601. PMID: 24901885, PMCID: PMC6148910.Peer-Reviewed Original ResearchConceptsCentral nervous systemCerebrospinal fluidHIV infectionCNS immune activationEarly HIV diagnosisHost genetic determinantsNeurologic complicationsNeurologic morbidityHIV diagnosisOpportunistic infectionsPersistent abnormalitiesHIV replicationImmune activationCNS dysfunctionCSF biomarkersNeurocognitive disordersHIV detectionNervous systemCognitive impairmentHIVSalutary effectsMild formEnd pointInfectionPotential mediators
2013
HIV and Neurocognitive Dysfunction
Spudich S. HIV and Neurocognitive Dysfunction. Current HIV/AIDS Reports 2013, 10: 235-243. PMID: 23860944, PMCID: PMC3732773, DOI: 10.1007/s11904-013-0171-y.Peer-Reviewed Original ResearchConceptsIrreversible CNS injuryEffective antiretroviral therapySpectrum of HIVQuality of lifeEffect of treatmentCommunity of patientsAntiretroviral therapyCNS infectionNeurologic injuryHIV infectionProgressive injuryImmune activationCNS injuryCognitive dysfunctionNeurocognitive disordersNeurocognitive dysfunctionHIVCognitive impairmentViral replicationInjuryBeneficial reductionDysfunctionInfectionDisordersPatientsCerebrospinal fluid neopterin decay characteristics after initiation of antiretroviral therapy
Yilmaz A, Yiannoutsos CT, Fuchs D, Price RW, Crozier K, Hagberg L, Spudich S, Gisslén M. Cerebrospinal fluid neopterin decay characteristics after initiation of antiretroviral therapy. Journal Of Neuroinflammation 2013, 10: 828. PMID: 23664008, PMCID: PMC3657550, DOI: 10.1186/1742-2094-10-62.Peer-Reviewed Original ResearchConceptsCSF neopterin levelsAntiretroviral therapyNeopterin levelsCerebrospinal fluidCSF neopterinHAD patientsMacrophage activationART-mediated viral suppressionCommencement of ARTHigher pre-ART levelsCSF neopterin concentrationsPre-ART levelsProlonged antiretroviral therapySuppressive antiretroviral therapySet-point levelsBlood neopterinHAD subjectsART initiationAsymptomatic HIVTreatment-naïveViral suppressionNeopterin concentrationsImmune activationMost HIVHIV
2012
Central Nervous System Viral Invasion and Inflammation During Acute HIV Infection
Valcour V, Chalermchai T, Sailasuta N, Marovich M, Lerdlum S, Suttichom D, Suwanwela NC, Jagodzinski L, Michael N, Spudich S, van Griensven F, de Souza M, Kim J, Ananworanich J. Central Nervous System Viral Invasion and Inflammation During Acute HIV Infection. The Journal Of Infectious Diseases 2012, 206: 275-282. PMID: 22551810, PMCID: PMC3490695, DOI: 10.1093/infdis/jis326.Peer-Reviewed Original ResearchConceptsHIV RNA levelsAcute HIV infectionCSF HIV RNA levelsCopies/mLHIV infectionCerebrospinal fluidHIV RNARNA levelsPlasma HIV RNA levelsCentral nervous system eventsHuman immunodeficiency virus (HIV) infectionCSF HIV RNAFiebig stages IIntrathecal immune activationAcute retroviral syndromeImmunodeficiency virus infectionNervous system eventsMagnetic resonance imagingMagnetic resonance spectroscopy characterizationCSF neopterinBrain inflammationCNS inflammationCSF levelsHIV transmissionImmune activationThe cerebrospinal fluid proteome in HIV infection: change associated with disease severity
Angel TE, Jacobs JM, Spudich SS, Gritsenko MA, Fuchs D, Liegler T, Zetterberg H, Camp DG, Price RW, Smith RD. The cerebrospinal fluid proteome in HIV infection: change associated with disease severity. Clinical Proteomics 2012, 9: 3. PMID: 22433316, PMCID: PMC3353874, DOI: 10.1186/1559-0275-9-3.Peer-Reviewed Original ResearchCNS HIV infectionHIV infectionCerebrospinal fluidChronic asymptomatic infectionSystemic HIV infectionNervous system infectionAmyloid precursor proteinCSF proteomic analysisCerebrospinal fluid proteomeCSF neopterinAntiretroviral therapyDifferent time pointsSystem infectionNeural injuryImmune activationMotor dysfunctionAsymptomatic infectionClinical spectrumCSF biomarkersCSF analysisDisease progressionCSF samplesNeuronal plasticityDisease severityInfection