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 ResearchMeSH KeywordsCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesCognitionHIV InfectionsHumansNeuroinflammatory DiseasesConceptsCombination 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 ResearchMeSH KeywordsAnti-Retroviral AgentsCD4-CD8 RatioCD8-Positive T-LymphocytesHIV InfectionsHumansRetrospective StudiesConceptsCD4/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 markersInfectionInjuryLong-term antiretroviral therapy initiated in acute HIV infection prevents residual dysfunction of HIV-specific CD8+ T cells
Takata H, Kakazu J, Mitchell J, Kroon E, Colby D, Sacdalan C, Bai H, Ehrenberg P, Geretz A, Buranapraditkun S, Pinyakorn S, Intasan J, Tipsuk S, Suttichom D, Prueksakaew P, Chalermchai T, Chomchey N, Phanuphak N, de Souza M, Michael N, Robb M, Haddad E, Crowell T, Vasan S, Valcour V, Douek D, Thomas R, Rolland M, Chomont N, Ananworanich J, Trautmann L, Teeratakulpisarn N, Pattanachaiwit S, Sriplienchan S, Tantivitayakul P, Kanaprach R, Ruxrungtham K, Dumrongpisutikul N, Rojnuckarin P, Chottanapund S, Poltavee K, Luekasemsuk T, Savadsuk H, Puttamsawin S, Benjapornpong K, Ratnaratorn N, Tangnaree K, Munkong C, Thaimanee R, Eamyoung P, Ubolyam S, Lerdlum S, Manasnayakorn S, Rerknimitr R, Sirivichayakul S, Wattanaboonyongcharoen P, Cowden J, Schuetz A, Akapirat S, Churikanont N, Getchalarat S, Hsu D, Turk E, Butterworth O, Milazzo M, Eller L, Ake J, Eller L, Spudich S, Fox L, Ratto-Kim S, DeGruttola V, Chinvarun Y, Sithinamsuwan P, Fletcher J, Shiramizu B, Schuetz A. Long-term antiretroviral therapy initiated in acute HIV infection prevents residual dysfunction of HIV-specific CD8+ T cells. EBioMedicine 2022, 84: 104253. PMID: 36088683, PMCID: PMC9471490, DOI: 10.1016/j.ebiom.2022.104253.Peer-Reviewed Original ResearchConceptsHIV-specific CD8Long-term antiretroviral therapyFunctional HIV-specific CD8Acute HIV infectionAntiretroviral therapyT cellsART initiationHIV infectionResidual dysfunctionVitro recallTCF-1 expressionChronic HIV infectionHIV remission strategiesT cell numbersT cell responsesInfection ex vivoStem cell-like propertiesCell numberCell-like propertiesART interruptionSpontaneous controllersViral reboundAcute infectionHIV remissionRemission strategiesNeuropathogenesis 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 consequencesBrainNeuropathogenesisIndividual Differences in CD4/CD8 T-Cell Ratio Trajectories and Associated Risk Profiles Modeled From Acute HIV Infection
Paul R, Cho K, Bolzenius J, Sacdalan C, Ndhlovu LC, Trautmann L, Krebs S, Tipsuk S, Crowell TA, Suttichom D, Colby DJ, Premeaux TA, Phanuphak N, Chan P, Kroon E, Vasan S, Hsu D, Carrico A, Valcour V, Ananworanich J, Robb ML, Ake JA, Sriplienchan S, Spudich S, Team F. Individual Differences in CD4/CD8 T-Cell Ratio Trajectories and Associated Risk Profiles Modeled From Acute HIV Infection. Psychosomatic Medicine 2022, 84: 976-983. PMID: 36162059, PMCID: PMC9553252, DOI: 10.1097/psy.0000000000001129.Peer-Reviewed Original ResearchMeSH KeywordsAnti-HIV AgentsCD4 Lymphocyte CountCD8-Positive T-LymphocytesHepatitis A Virus Cellular Receptor 2HIV InfectionsHumansIndividualityViral LoadConceptsAcute HIV infectionCD4/CD8 T-cell ratioCD8 T-cell ratioAntiretroviral therapyT-cell countsT-cell recoveryT cell ratioHigh viral loadViral loadHigh CD8Slower CD4HIV infectionLower white blood cell countWeeks of ARTRisk profileWhite blood cell countT-cell trajectoriesMedian viral loadStandard antiretroviral therapyBlood cell countLower eosinophil countsWorse mental healthAHI participantsART onsetFiebig I
2021
Compartmentalization of cerebrospinal fluid inflammation across the spectrum of untreated HIV-1 infection, central nervous system injury and viral suppression
Gisslen M, Keating SM, Spudich S, Arechiga V, Stephenson S, Zetterberg H, Di Germanio C, Blennow K, Fuchs D, Hagberg L, Norris PJ, Peterson J, Shacklett BL, Yiannoutsos CT, Price RW. Compartmentalization of cerebrospinal fluid inflammation across the spectrum of untreated HIV-1 infection, central nervous system injury and viral suppression. PLOS ONE 2021, 16: e0250987. PMID: 33983973, PMCID: PMC8118251, DOI: 10.1371/journal.pone.0250987.Peer-Reviewed Original ResearchMeSH KeywordsAdultAnti-Retroviral AgentsAntiretroviral Therapy, Highly ActiveBiomarkersCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesCentral Nervous SystemCross-Sectional StudiesFemaleHIV InfectionsHIV-1HumansInflammationLeukocyte CountMaleMiddle AgedNeurofilament ProteinsRNA, ViralSerum AlbuminSustained Virologic ResponseConceptsHIV-1 infectionHIV-associated dementiaPrimary HIV-1 infectionBlood CD4CSF inflammationViral suppressionInflammatory biomarkersCNS injuryViral controlT lymphocytesCSF white blood cell countUntreated primary HIV-1 infectionBlood HIV-1 RNACentral nervous system inflammationCerebrospinal fluid inflammatory biomarkersCSF neurofilament light chainHIV-1 seronegative controlsHIV-1-infected subjectsHIV-1-uninfected controlsHIV-1 RNA concentrationsUntreated HIV-1 infectionWhite blood cell countBlood-brain barrier permeabilityCentral nervous system injuryCSF inflammatory response
2020
Determinants of suboptimal CD4+ T cell recovery after antiretroviral therapy initiation in a prospective cohort of acute HIV‐1 infection
Handoko R, Colby DJ, Kroon E, Sacdalan C, de Souza M, Pinyakorn S, Prueksakaew P, Munkong C, Ubolyam S, Akapirat S, Chiarella J, Krebs S, Sereti I, Valcour V, Paul R, Michael NL, Phanuphak N, Ananworanich J, Spudich S, Team T. Determinants of suboptimal CD4+ T cell recovery after antiretroviral therapy initiation in a prospective cohort of acute HIV‐1 infection. Journal Of The International AIDS Society 2020, 23: e25585. PMID: 32949118, PMCID: PMC7507109, DOI: 10.1002/jia2.25585.Peer-Reviewed Original ResearchConceptsAcute HIV infectionCD4/CD8 ratioSuboptimal CD4 recoveryAntiretroviral therapyCD4 countImmune recoveryCD4 recoveryCD8 ratioStudy visitAcute HIV-1 infectionPre-ART CD4 countLower CD8 countsPlasma viral suppressionSuboptimal immune recoveryAntiretroviral therapy initiationT-cell countsT-cell recoveryHIV-1 infectionCopies/mLLower IL-6Cells/ART initiationCD4 rateCD8 countsChronic HIV
2017
High 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 ResearchMeSH KeywordsCD8-Positive T-LymphocytesCerebrospinal FluidHIV AntigensHIV InfectionsHumansImmunophenotypingT-Lymphocyte SubsetsConceptsAcute 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 epitopes
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 and HIV-Specific CD8+ T Cells in Cerebrospinal Fluid of HIV Controllers and Noncontrollers
Ganesh A, Lemongello D, Lee E, Peterson J, McLaughlin BE, Ferre AL, Gillespie GM, Fuchs D, Deeks SG, Hunt PW, Price RW, Spudich SS, Shacklett BL. Immune Activation and HIV-Specific CD8+ T Cells in Cerebrospinal Fluid of HIV Controllers and Noncontrollers. AIDS Research And Human Retroviruses 2016, 32: 791-800. PMID: 27019338, PMCID: PMC4971411, DOI: 10.1089/aid.2015.0313.Peer-Reviewed Original ResearchMeSH KeywordsADP-ribosyl Cyclase 1Anti-HIV AgentsAntiretroviral Therapy, Highly ActiveCD4 Lymphocyte CountCD8-Positive T-LymphocytesDisease ResistanceGene ExpressionHIV InfectionsHIV-1HLA-DR AntigensHost-Pathogen InteractionsHumansLeukocyte Common AntigensLymphocyte ActivationReceptors, CCR5Receptors, CCR7RNA, ViralViral LoadViremiaConceptsCentral nervous systemHIV controllersAntiretroviral therapyT cellsCerebrospinal fluidViral loadCopies/HIV-specific T cellsMajor histocompatibility complex class IActivation markers CD38CSF viral loadHIV-specific CD8Undetectable plasma viremiaExpression of CCR5Majority of HIVPlasma viral loadEffector memory cellsHIV-negative controlsHistocompatibility complex class IAbsence of therapyComplex class ILong-term controlPlasma viremiaElite controllersHIV infection
2014
Peripheral Neuropathy in Primary HIV Infection Associates With Systemic and Central Nervous System Immune Activation
Wang SX, Ho EL, Grill M, Lee E, Peterson J, Robertson K, Fuchs D, Sinclair E, Price RW, Spudich S. Peripheral Neuropathy in Primary HIV Infection Associates With Systemic and Central Nervous System Immune Activation. JAIDS Journal Of Acquired Immune Deficiency Syndromes 2014, 66: 303-310. PMID: 24732871, PMCID: PMC4147038, DOI: 10.1097/qai.0000000000000167.Peer-Reviewed Original ResearchConceptsPrimary HIV infectionPeripheral neuropathyCerebrospinal fluidHIV infectionHIV transmissionPN subjectsCentral nervous system immune activationCSF white blood cell countPlasma HIV RNA levelsSigns of PNWhite blood cell countChronic HIV infectionHIV RNA levelsCD8 T lymphocytesDetailed neurologic examinationSymptomatic peripheral neuropathyBlood cell countChemoattractant protein-1Blood CD4Blood neopterinCD8 countsCSF neopterinBilateral findingsFrequent complicationAnalysis of blood
2013
Single-copy assay quantification of HIV-1 RNA in paired cerebrospinal fluid and plasma samples from elite controllers
Dahl V, Peterson J, Spudich S, Lee E, Shacklett BL, Price RW, Palmer S. Single-copy assay quantification of HIV-1 RNA in paired cerebrospinal fluid and plasma samples from elite controllers. AIDS 2013, 27: 1145-1149. PMID: 23211774, PMCID: PMC4004626, DOI: 10.1097/qad.0b013e32835cf235.Peer-Reviewed Original ResearchConceptsHIV-1 RNACentral nervous systemHIV-1 RNA quantificationElite controllersCerebrospinal fluidPlasma samplesCSF samplesHIV-1 RNA concentrationsHIV-1-infected individualsConcurrent plasma samplesSingle-copy assayRNA quantificationAntiretroviral therapyCopies/HIV-1Rare subsetNervous systemRNA concentrationClinical assaysSensitive assayAssaysRNATherapyInfectionBlood
2011
Raltegravir Treatment Intensification Does Not Alter Cerebrospinal Fluid HIV-1 Infection or Immunoactivation in Subjects on Suppressive Therapy
Dahl V, Lee E, Peterson J, Spudich SS, Leppla I, Sinclair E, Fuchs D, Palmer S, Price RW. Raltegravir Treatment Intensification Does Not Alter Cerebrospinal Fluid HIV-1 Infection or Immunoactivation in Subjects on Suppressive Therapy. The Journal Of Infectious Diseases 2011, 204: 1936-1945. PMID: 22021620, PMCID: PMC3209817, DOI: 10.1093/infdis/jir667.Peer-Reviewed Original ResearchConceptsHIV-1 RNA levelsHIV-1 RNAImmune activationRaltegravir intensificationRNA levelsPlasma human immunodeficiency virus type 1 (HIV-1) RNACSF HIV-1 RNA levelsMedian HIV-1 RNA levelT-cell surface antigen expressionHuman immunodeficiency virus type 1 (HIV-1) RNAOpen-label pilot studySingle-copy assayHIV RNA levelsCerebrospinal fluid infectionHIV-1 infectionCentral nervous systemBaseline viral suppressionSurface antigen expressionT cell activationCSF neopterinIntrathecal immunoactivationSuppressive therapyAntiretroviral therapyTreatment intensificationViral suppression
2008
Failure of atorvastatin to modulate CSF HIV-1 infection
Probasco JC, Spudich SS, Critchfield J, Lee E, Lollo N, Deeks SG, Price RW. Failure of atorvastatin to modulate CSF HIV-1 infection. Neurology 2008, 71: 521-524. PMID: 18695163, PMCID: PMC2676982, DOI: 10.1212/01.wnl.0000325006.84658.e7.Peer-Reviewed Original ResearchConceptsHIV-1 infectionHIV-1 RNA levelsT-cell countsCell countIntrathecal immunoactivationNeopterin concentrationsBlood lipidsBlood HIV-1 RNA levelCSF HIV-1 RNA levelsCSF white blood cell countCNS HIV-1 infectionSystemic HIV-1 infectionSingle-arm pilot studyWhite blood cell countPilot studyAntiretroviral-naïve subjectsCells/mulRNA levelsUntreated systemic infectionT-lymphocyte countsSmall uncontrolled studiesEffect of atorvastatinHMG-CoA reductase inhibitorsWeeks of treatmentHIV-1 RNAAntiretroviral Treatment Effect on Immune Activation Reduces Cerebrospinal Fluid HIV-1 Infection
Sinclair E, Ronquillo R, Lollo N, Deeks SG, Hunt P, Yiannoutsos CT, Spudich S, Price RW. Antiretroviral Treatment Effect on Immune Activation Reduces Cerebrospinal Fluid HIV-1 Infection. JAIDS Journal Of Acquired Immune Deficiency Syndromes 2008, 47: 544-552. PMID: 18362693, PMCID: PMC3480328, DOI: 10.1097/qai.0b013e318162754f.Peer-Reviewed Original ResearchConceptsPlasma HIV-1 RNACD8 T cell activationHIV-1 RNACSF HIV-1 RNA levelsHIV-1 RNA levelsT cell activationWhite blood cellsHIV-1 concentrationsAntiretroviral therapyHIV-1 infectionCerebrospinal fluidCD8 activationCSF neopterinViremic groupImmune activationCopies/HIV-1CD38/HLA-DR expressionCSF HIV-1 RNA concentrationsHIV-1-infected subjectsSystemic HIV-1 infectionHIV-1 RNA concentrationsHuman leukocyte antigen-DRCSF white blood cellsCoexpression of CD38