2024
Changes in cerebrospinal fluid proteins across the spectrum of untreated and treated chronic HIV-1 infection
Hu Z, Cinque P, Dravid A, Hagberg L, Yilmaz A, Zetterberg H, Fuchs D, Gostner J, Blennow K, Spudich S, Kincer L, Zhou S, Joseph S, Swanstrom R, Price R, Gisslén M. Changes in cerebrospinal fluid proteins across the spectrum of untreated and treated chronic HIV-1 infection. PLOS Pathogens 2024, 20: e1012470. PMID: 39316609, PMCID: PMC11469498, DOI: 10.1371/journal.ppat.1012470.Peer-Reviewed Original ResearchConceptsHIV-1 infectionHIV-associated dementiaCerebrospinal fluidCerebrospinal fluid proteinCerebrospinal fluid HIV-1 RNAImpact of HIV-1 infectionTreating chronic HIV-1 infectionChronic HIV-1 infectionHIV-1 RNAHIV-1 progressionTreat chronic infectionsInflammatory cell lineagesNeurofilament light chain proteinCSF escapeChronic infectionHIV-1Light chain proteinProtein changesClinical centersCNS injuryCSF proteinClinical informationCell lineagesInfectionCerebrospinal fluid proteome
2022
Immunological, Cognitive, and Psychiatric Outcomes After Initiating Efavirenz- and Dolutegravir-based Antiretroviral Therapy During Acute Human Immunodeficiency Virus Infection
Chan P, Yoon B, Colby D, Kroon E, Sacdalan C, Sriplienchan S, Pinyakorn S, Ananworanich J, Valcour V, Vasan S, Hsu D, Phanuphak N, Paul R, Spudich S. Immunological, Cognitive, and Psychiatric Outcomes After Initiating Efavirenz- and Dolutegravir-based Antiretroviral Therapy During Acute Human Immunodeficiency Virus Infection. Clinical Infectious Diseases 2022, 76: e718-e726. PMID: 35687498, PMCID: PMC9907536, DOI: 10.1093/cid/ciac466.Peer-Reviewed Original ResearchConceptsAcute HIV-1 infectionT-cell countsDTG-based antiretroviral therapyAntiretroviral therapyDTG groupEFV groupWeek 96Week 24CD4/CD8 ratioNucleoside reverse transcriptase inhibitorHuman immunodeficiency virus type 1Immunodeficiency virus type 1Fiebig stages IPlasma viral suppressionAcute HIV infectionTreatment-naive individualsHIV-1 infectionPatient Health QuestionnaireReverse transcriptase inhibitorVirus type 1Greater incrementART regimensCD8 ratioViral suppressionHIV infection
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 responseClinical and laboratory impact of concomitant syphilis infection during acute HIV
Chan P, Colby D, Kroon E, Sacdalan C, Pinyakorn S, Paul R, Robb M, Valcour V, Ananworanich J, Marra C, Spudich S. Clinical and laboratory impact of concomitant syphilis infection during acute HIV. HIV Medicine 2021, 22: 502-511. PMID: 33728759, DOI: 10.1111/hiv.13079.Peer-Reviewed Original ResearchConceptsAcute HIV-1T lymphocyte levelsVenereal Disease Research LaboratoryUntreated syphilisHistory of syphilisHIV-1Higher plasma HIV-1 RNACD4 T-lymphocyte levelsPlasma HIV-1 RNAHIV-1 RNA levelsCognitive performanceCD4 T lymphocytesHIV-1 infectionHIV-1 RNAImpaired cognitive performanceAcute HIVAHI participantsFiebig stagesIncident syphilisPrior syphilisSerum TreponemaSyphilis infectionChronic infectionDisease measuresSyphilis statusCognitive trajectories after treatment in acute HIV infection
Chan P, Kerr SJ, Kroon E, Colby D, Sacdalan C, Hellmuth J, Reiss P, Vasan S, Ananworanich J, Valcour V, Spudich S, Paul R. Cognitive trajectories after treatment in acute HIV infection. AIDS 2021, 35: 883-888. PMID: 33534200, DOI: 10.1097/qad.0000000000002831.Peer-Reviewed Original ResearchConceptsAcute HIV-1 infectionAntiretroviral therapyWeek 288Week 96Cognitive performanceAcute HIV infectionSuppressive antiretroviral therapyHIV-1 infectionTrajectory subgroupsWorse depressive symptomsWorse baseline cognitive performanceImpaired cognitive performanceFine motor speedAHI diagnosisViral suppressionHIV infectionWeek 12Baseline cognitive performanceLower baseline performanceHIV-1Depressive symptomsCognitive symptomsPosthoc analysisPsychomotor speedCognitive outcomes
2020
Minimal detection of cerebrospinal fluid escape after initiation of antiretroviral therapy in acute HIV-1 infection.
Handoko R, Chan P, Jagodzinski L, Pinyakorn S, Ubolyam S, Phanuphak N, Sacdalan C, Kroon E, Dumrongpisutikul N, Paul R, Valcour V, Ananworanich J, Vasan S, Spudich S. Minimal detection of cerebrospinal fluid escape after initiation of antiretroviral therapy in acute HIV-1 infection. AIDS 2020, 35: 777-782. PMID: 33306551, PMCID: PMC7969409, DOI: 10.1097/qad.0000000000002786.Peer-Reviewed Original ResearchConceptsAcute HIV-1 infectionHIV-1 RNACentral nervous systemCSF escapeAntiretroviral therapyHIV-1 infectionWeek 96Week 24HIV-1CSF HIV-1 RNAInitiation of ARTLong-term neurological outcomePlasma HIV-1 RNAWeeks of ARTProspective cohort studyPersistence of HIVHIV-1 persistenceLevels of CSFYears of treatmentHIV-1 replicationNeurological outcomeCohort studyVoluntary counselingChronic infectionEarly treatmentDeterminants 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 HIVA randomized trial of vorinostat with treatment interruption after initiating antiretroviral therapy during acute HIV-1 infection
Kroon EDMB, Ananworanich J, Pagliuzza A, Rhodes A, Phanuphak N, Trautmann L, Mitchell JL, Chintanaphol M, Intasan J, Pinyakorn S, Benjapornpong K, Chang JJ, Colby DJ, Chomchey N, Fletcher JLK, Eubanks K, Yang H, Kapson J, Dantanarayana A, Tennakoon S, Gorelick RJ, Maldarelli F, Robb ML, Kim JH, Spudich S, Chomont N, Phanuphak P, Lewin SR, de Souza MS, Teams F. A randomized trial of vorinostat with treatment interruption after initiating antiretroviral therapy during acute HIV-1 infection. Journal Of Virus Eradication 2020, 6: 100004. PMID: 33251022, PMCID: PMC7646672, DOI: 10.1016/j.jve.2020.100004.Peer-Reviewed Original ResearchAcute HIV infectionAntiretroviral therapyTreatment interruptionViral loadAcute HIV-1 infectionHIV RNA copies/Open-label pilot studyPeripheral blood mononuclear cellsControl HIV replicationSubsequent treatment interruptionTotal HIV DNASerious adverse eventsHIV viral loadPlasma viral loadRNA copies/HIV-1 infectionBlood mononuclear cellsCopies/mLProportion of participantsCell-associated RNAAlternative treatment strategiesHistone deacetylase inhibitorsVL reboundHIV RNAViral reboundFeasibility and safety of research sigmoid colon biopsy in a cohort of Thai men who have sex with men with acute HIV-1
Chintanaphol M, Sacdalan C, Pinyakorn S, Rerknimitr R, Ridtitid W, Prueksapanich P, Sereti I, Schuetz A, Crowell TA, Colby DJ, Robb ML, Phanuphak N, Ananworanich J, Spudich SS, Kroon E. Feasibility and safety of research sigmoid colon biopsy in a cohort of Thai men who have sex with men with acute HIV-1. Journal Of Virus Eradication 2020, 6: 7-10. PMID: 32175085, PMCID: PMC7043900, DOI: 10.1016/s2055-6640(20)30011-x.Peer-Reviewed Original ResearchAcute HIV-1 infectionGut-associated lymphoid tissueHIV-1 reservoirSigmoid colon biopsiesAdverse eventsAE riskSigmoid colonColon biopsiesHIV-1CD4 T-cell depletionCD4 T-cell countAcute HIV-1Mild rectal bleedingAdverse event incidenceT-cell countsHigh viral replicationT-cell depletionHIV-1 infectionHIV-1 RNATime of biopsyIncidence rate ratiosRectal bleedingAbdominal discomfortEvent incidenceViral load
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 diseasesDeep Sequencing Reveals Central Nervous System Compartmentalization in Multiple Transmitted/Founder Virus Acute HIV-1 Infection
Tovanabutra S, Sirijatuphat R, Pham PT, Bonar L, Harbolick EA, Bose M, Song H, Chang D, Oropeza C, O’Sullivan A, Balinang J, Kroon E, Colby DJ, Sacdalan C, Hellmuth J, Chan P, Prueksakaew P, Pinyakorn S, Jagodzinski LL, Sutthichom D, Pattamaswin S, de Souza M, Gramzinski RA, Kim JH, Michael NL, Robb ML, Phanuphak N, Ananworanich J, Valcour V, Kijak GH, Sanders-Buell E, Spudich S, Core T, Team T. Deep Sequencing Reveals Central Nervous System Compartmentalization in Multiple Transmitted/Founder Virus Acute HIV-1 Infection. Cells 2019, 8: 902. PMID: 31443253, PMCID: PMC6721674, DOI: 10.3390/cells8080902.Peer-Reviewed Original ResearchConceptsAcute HIV-1 infectionCentral nervous systemHIV-1 infectionCerebrospinal fluidCNS compartmentalizationHIV-1HIV-1 compartmentalizationHIV-1 exposureHIV-1 neuropathogenesisHIV-1 reservoirSingle-genome sequencingHIV reservoirFounder virusesRemission strategiesNeurological impairmentNervous systemF infectionsViral replicationInfectionPotential long-term implicationsNext-generation sequencingEnvelope geneTissue compartmentsF variantLong-term implications
2018
CSF concentrations of soluble TREM2 as a marker of microglial activation in HIV-1 infection
Gisslén M, Heslegrave A, Veleva E, Yilmaz A, Andersson LM, Hagberg L, Spudich S, Fuchs D, Price RW, Zetterberg H. CSF concentrations of soluble TREM2 as a marker of microglial activation in HIV-1 infection. Neurology Neuroimmunology & Neuroinflammation 2018, 6: e512. PMID: 30568991, PMCID: PMC6278890, DOI: 10.1212/nxi.0000000000000512.Peer-Reviewed Original ResearchConceptsHIV-1 infectionHIV-negative controlsMicroglial activationNeuronal injuryCSF concentrationsUntreated HIV-1-infected patientsHIV-1 disease severityHIV-1-infected adultsMacrophage/microglial activationHIV-1-infected patientsRetrospective cross-sectional studyUntreated HIV-1 infectionCNS immune activationCSF sTREM2 levelsSuppressive antiretroviral treatmentT-cell countsMicroglial activation markersT cell lossLevels of CSFNeurofilament light proteinCross-sectional studyCSF sTREM2STREM2 levelsAntiretroviral treatmentActivation markers
2017
Neurofilament light chain protein as a marker of neuronal injury: review of its use in HIV-1 infection and reference values for HIV-negative controls
Yilmaz A, Blennow K, Hagberg L, Nilsson S, Price RW, Schouten J, Spudich S, Underwood J, Zetterberg H, Gisslén M. Neurofilament light chain protein as a marker of neuronal injury: review of its use in HIV-1 infection and reference values for HIV-negative controls. Expert Review Of Molecular Diagnostics 2017, 17: 761-770. PMID: 28598205, DOI: 10.1080/14737159.2017.1341313.Peer-Reviewed Original ResearchConceptsHIV-negative controlsCSF NFL concentrationsNeuronal injuryNeurofilament proteinNfL concentrationsNeurofilament light chain proteinHIV CNS infectionEarly acute phaseHIV-1 infectionAge-related upper limitCNS infectionsSevere immunosuppressionAntiretroviral treatmentHIV infectionNeuronal damageAcute phaseCNS injuryCSF biomarkersLumbar punctureCSF concentrationsNerve conductionNeurological conditionsSensitive markerNeurological diseasesLight chain proteinProminent motor abnormalities in Thai men and women with presumed subtype CRF01_AE HIV-1 infection improve with antiretroviral therapy (P2.304)
Silverman A, Chan P, Paul R, Hellmuth J, Sithinamsuwan P, Ananworanich J, Phanuphak N, Fletcher J, Chalermchai T, Tipsuk S, Suttichom D, Valcour V, Spudich S. Prominent motor abnormalities in Thai men and women with presumed subtype CRF01_AE HIV-1 infection improve with antiretroviral therapy (P2.304). Neurology 2017, 88 DOI: 10.1212/wnl.88.16_supplement.p2.304.Peer-Reviewed Original ResearchImmediate 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
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 course
2013
Cellular Composition of Cerebrospinal Fluid in HIV-1 Infected and Uninfected Subjects
Ho EL, Ronquillo R, Altmeppen H, Spudich SS, Price RW, Sinclair E. Cellular Composition of Cerebrospinal Fluid in HIV-1 Infected and Uninfected Subjects. PLOS ONE 2013, 8: e66188. PMID: 23822975, PMCID: PMC3688831, DOI: 10.1371/journal.pone.0066188.Peer-Reviewed Original ResearchConceptsT cellsCerebrospinal fluidHIV infectionMajor cellular componentCD8 ratioUninfected subjectsNK cellsB cellsHIV-1 infectionCellular compositionMulti-parameter flow cytometrySpectrum of diseaseCentral nervous systemCSF CD4Lymphocyte subsetsPeripheral lossPeripheral bloodHealthy controlsHIV-1Absolute countsCD4HIVPreferential traffickingNervous systemCD8Progressive Increase in Cerebrospinal Fluid (CSF) Neopterin and Relation to Neuropsychological Performance during Primary HIV-1 Infection Prior to Antiretroviral Therapy (P06.189)
Suh J, Robertson K, Peterson J, Lee E, Kyriakides T, Li F, Fuchs D, Price R, Hagberg L, Gisslen M, Spudich S. Progressive Increase in Cerebrospinal Fluid (CSF) Neopterin and Relation to Neuropsychological Performance during Primary HIV-1 Infection Prior to Antiretroviral Therapy (P06.189). Neurology 2013, 80 DOI: 10.1212/wnl.80.7_supplement.p06.189.Peer-Reviewed Original Research
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 suppressionMinocycline fails to modulate cerebrospinal fluid HIV infection or immune activation in chronic untreated HIV-1 infection: results of a pilot study
Ho EL, Spudich SS, Lee E, Fuchs D, Sinclair E, Price RW. Minocycline fails to modulate cerebrospinal fluid HIV infection or immune activation in chronic untreated HIV-1 infection: results of a pilot study. AIDS Research And Therapy 2011, 8: 17. PMID: 21569420, PMCID: PMC3117676, DOI: 10.1186/1742-6405-8-17.Peer-Reviewed Original ResearchCerebrospinal fluidHIV infectionImmune activationPilot studyCSF white blood cell countBlood HIV-1 RNAChronic untreated HIV infectionUntreated HIV-1 infectionWhite blood cell countCell surface activation markersCNS HIV infectionUntreated HIV infectionHIV-1 infectionHIV-1 RNABlood cell countBlood T lymphocytesConclusionsThis pilot studyBlood neopterinCSF CCL2Adjuvant therapyAntiretroviral therapyViremic subjectsActivation markersBlood biomarkersBrain injury