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 ResearchMeSH KeywordsAdultAIDS Dementia ComplexBiomarkersCerebrospinal Fluid ProteinsChronic DiseaseFemaleHIV InfectionsHIV-1HumansMaleMiddle AgedConceptsHIV-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 proteomeCentral Nervous System Effects of Early HIV Infection and Consequences of Antiretroviral Therapy Initiation during Acute HIV
Chan P, Spudich S. Central Nervous System Effects of Early HIV Infection and Consequences of Antiretroviral Therapy Initiation during Acute HIV. Viruses 2024, 16: 1082. PMID: 39066244, PMCID: PMC11281648, DOI: 10.3390/v16071082.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsMeSH KeywordsAIDS Dementia ComplexAnti-HIV AgentsAnti-Retroviral AgentsAntiretroviral Therapy, Highly ActiveCentral Nervous SystemHIV InfectionsHumansConceptsEarly HIV infectionCentral nervous systemHIV infectionEffects of early HIV infectionIncrease awareness of HIV infectionCentral nervous system opportunistic infectionsImmediate initiation of antiretroviral therapyInitiation of antiretroviral therapyAwareness of HIV infectionCentral nervous system complicationsCentral nervous system involvementAntiretroviral therapy initiationCentral nervous system effectsLong-term neuroprotectionHIV-associated dementiaOvert clinical manifestationsYears of infectionMulti-organ diseaseNucleic acid testingAcute HIVHIV neuroinvasionHIV RNAAntiretroviral therapyOpportunistic infectionsTherapy initiation
2021
Cerebrospinal Fluid Viral Load Across the Spectrum of Untreated Human Immunodeficiency Virus Type 1 (HIV-1) Infection: A Cross-Sectional Multicenter Study
Ulfhammer G, Edén A, Antinori A, Brew BJ, Calcagno A, Cinque P, De Zan V, Hagberg L, Lin A, Nilsson S, Oprea C, Pinnetti C, Spudich S, Trunfio M, Winston A, Price RW, Gisslén M. Cerebrospinal Fluid Viral Load Across the Spectrum of Untreated Human Immunodeficiency Virus Type 1 (HIV-1) Infection: A Cross-Sectional Multicenter Study. Clinical Infectious Diseases 2021, 75: 493-502. PMID: 34747481, PMCID: PMC9427147, DOI: 10.1093/cid/ciab943.Peer-Reviewed Original ResearchConceptsCSF HIV RNAWhite blood cell countPlasma HIV RNAUntreated human immunodeficiency virus type 1 (HIV-1) infectionHuman immunodeficiency virus type 1 (HIV-1) infectionCSF white blood cell countVirus type 1 infectionHIV RNACopies/mLType 1 infectionMulticenter studyOpportunistic central nervous system infectionsCerebrospinal fluid HIV RNACerebrospinal fluid viral loadHigher CSF HIV RNALog10 copies/mLCentral nervous system infectionCross-sectional multicenter studyHIV RNA quantificationNervous system infectionTreatment-naive adultsBlood cell countLarge multicenter studyCNS compartmentalizationCSF discordance
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 ResearchCerebrospinal Fluid Concentrations of the Synaptic Marker Neurogranin in Neuro-HIV and Other Neurological Disorders
Yilmaz A, Fuchs D, Price RW, Spudich S, Blennow K, Zetterberg H, Gisslén M. Cerebrospinal Fluid Concentrations of the Synaptic Marker Neurogranin in Neuro-HIV and Other Neurological Disorders. Current HIV/AIDS Reports 2019, 16: 76-81. PMID: 30649659, PMCID: PMC6420419, DOI: 10.1007/s11904-019-00420-1.Peer-Reviewed Original ResearchConceptsCSF neurograninCerebrospinal fluidProinflammatory cytokines IL-1βGroup of HIVLewy body dementiaCerebrospinal fluid concentrationsCytokines IL-1βLevels of neurograninNeurogranin concentrationsNeuro-HIVHIV neuropathogenesisSynaptic injuryHIV infectionIL-1βNeurocognitive disordersFrontal cortexParkinson's diseaseUninfected controlsReviewThe aimAlzheimer's diseaseNeurological disordersFrontotemporal dementiaNeurodegenerative disordersFluid concentrationsHIV
2018
Residency Training: Progressive gait difficulty and incontinence in a 40-year-old man with HIV
Silverman A, O'Meara T, Le L, Robertson K, Spudich S. Residency Training: Progressive gait difficulty and incontinence in a 40-year-old man with HIV. Neurology 2018, 91: 1065-1070. PMID: 30510020, PMCID: PMC6282230, DOI: 10.1212/wnl.0000000000006619.Peer-Reviewed Original ResearchCSF 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
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 changesInfectionImpairmentCROI 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 ResearchMeSH KeywordsAIDS Dementia ComplexBrainCentral Nervous System InfectionsHIV InfectionsHumansNeuroimagingStrokeConceptsCentral 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
2015
Compartmentalized Replication of R5 T Cell-Tropic HIV-1 in the Central Nervous System Early in the Course of Infection
Sturdevant CB, Joseph SB, Schnell G, Price RW, Swanstrom R, Spudich S. Compartmentalized Replication of R5 T Cell-Tropic HIV-1 in the Central Nervous System Early in the Course of Infection. PLOS Pathogens 2015, 11: e1004720. PMID: 25811757, PMCID: PMC4374811, DOI: 10.1371/journal.ppat.1004720.Peer-Reviewed Original ResearchMeSH KeywordsAdultAIDS Dementia ComplexCell LineCentral Nervous SystemFemaleHIV-1HumansMaleMiddle AgedRNA, ViralViral TropismVirus ReplicationConceptsCentral nervous systemSingle genome amplificationHIV-1 RNA concentrationsHIV-1 replicationInflammatory responseViral replicationHIV-1Nervous systemCSF HIV-1 RNA concentrationsIndependent HIV-1 replicationT-cell-tropic HIV-1Full-length env sequencesART-naïve subjectsCNS viral replicationCSF inflammatory responseTime pointsLocal viral replicationYears of infectionMonths of infectionRNA concentrationViral populationsCellular inflammatory responseCourse of infectionTransmitted variantsPopulation of subjectsNeuropathogenesis 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
2014
Treatment of HIV in the CNS: Effects of Antiretroviral Therapy and the Promise of Non-Antiretroviral Therapeutics
Peluso MJ, Spudich S. Treatment of HIV in the CNS: Effects of Antiretroviral Therapy and the Promise of Non-Antiretroviral Therapeutics. Current HIV/AIDS Reports 2014, 11: 353-362. PMID: 25063356, DOI: 10.1007/s11904-014-0223-y.Peer-Reviewed Original ResearchMeSH KeywordsAIDS Dementia ComplexAnti-HIV AgentsBiomarkersCentral Nervous SystemDrug Therapy, CombinationHIV InfectionsHIV-1HumansInflammationRNA, ViralConceptsCentral nervous systemAntiretroviral therapyNew neurologic abnormalitiesTrajectory of HIVAIDS dementia complexSpectrum of HIVTreatment of HIVPersistent handViral suppressionNeurologic manifestationsAsymptomatic diseaseHIV infectionNeurologic abnormalitiesNeurocognitive disordersNeurologic diseaseNeurocognitive dysfunctionTherapeutic modalitiesNervous systemHIVSevere impairmentTherapyDiseasePatientsDysfunctionPathophysiologyCROI 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 ResearchMeSH KeywordsAIDS Dementia ComplexAnti-HIV AgentsDrug-Related Side Effects and Adverse ReactionsHIV InfectionsHumansConceptsCentral 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
Approach to Cerebrospinal Fluid (CSF) Biomarker Discovery and Evaluation in HIV Infection
Price RW, Peterson J, Fuchs D, Angel TE, Zetterberg H, Hagberg L, Spudich S, Smith RD, Jacobs JM, Brown JN, Gisslen M. Approach to Cerebrospinal Fluid (CSF) Biomarker Discovery and Evaluation in HIV Infection. Journal Of Neuroimmune Pharmacology 2013, 8: 1147-1158. PMID: 23943280, PMCID: PMC3889225, DOI: 10.1007/s11481-013-9491-3.Peer-Reviewed Original ResearchConceptsHIV infectionCentral nervous system infectionSystemic HIV infectionNervous system infectionCNS disease progressionCerebrospinal fluid biomarkersCross-sectional studyInteraction of HIVCSF biomarker studiesCNS infectionsDisease activitySystem infectionAntiretroviral treatmentClinical stagingNeural injuryCSF biomarkersNeurological consequencesFluid biomarkersDisease progressionMore accurate diagnosisNeuropsychological test performanceNovel biomarkersAccurate diagnosisBiomarker concentrationsInfection
2012
Cerebrospinal fluid HIV escape associated with progressive neurologic dysfunction in patients on antiretroviral therapy with well controlled plasma viral load
Peluso MJ, Ferretti F, Peterson J, Lee E, Fuchs D, Boschini A, Gisslén M, Angoff N, Price RW, Cinque P, Spudich S. Cerebrospinal fluid HIV escape associated with progressive neurologic dysfunction in patients on antiretroviral therapy with well controlled plasma viral load. AIDS 2012, 26: 1765-1774. PMID: 22614889, PMCID: PMC3881435, DOI: 10.1097/qad.0b013e328355e6b2.Peer-Reviewed Original ResearchConceptsCSF HIV RNAAntiretroviral therapyHIV RNACopies/CSF escapeNeurologic abnormalitiesCerebrospinal fluidMedian CD4 T-cell countDetectable CSF HIV RNAMedian plasma HIV RNACD4 T-cell countCentral nervous system exposureNew neurologic abnormalitiesPlasma HIV levelsPlasma HIV RNAProgressive neurologic abnormalitiesStable ART regimenPlasma viral loadT-cell countsElevated CSF proteinRetrospective case seriesProgressive neurologic dysfunctionUrban medical centerCSF RNAHIV escapeHIV-1-Related Central Nervous System Disease: Current Issues in Pathogenesis, Diagnosis, and Treatment
Spudich S, González-Scarano F. HIV-1-Related Central Nervous System Disease: Current Issues in Pathogenesis, Diagnosis, and Treatment. Cold Spring Harbor Perspectives In Medicine 2012, 2: a007120. PMID: 22675662, PMCID: PMC3367536, DOI: 10.1101/cshperspect.a007120.Peer-Reviewed Original ResearchConceptsHIV infectionLate-stage HIV infectionCentral nervous system injuryOptimal antiretroviral therapyNeuropathogenesis of HIVTreatment of HIVNervous system injuryLong-term survivalAntiretroviral therapyCNS complicationsAntiretroviral medicationsViral neuroinvasionSystem injuryCNS injuryClinical studiesNeurological abnormalitiesUnderresourced settingsNeuropsychological testingHIVInfectionSubstantial proportionTherapyInjuryTreatmentCurrent eraNeurologic complications of HIV infection.
Spudich SS, Ances BM. Neurologic complications of HIV infection. Topics In Antiviral Medicine 2012, 20: 41-7. PMID: 22710906, PMCID: PMC6148861.Peer-Reviewed Original ResearchMeSH KeywordsAIDS Dementia ComplexAnti-Retroviral AgentsHIV-1HumansNeuroimagingNeuropsychological TestsConceptsCentral nervous systemHIV infectionNervous systemBrain microglial activationWarrants further studyAntiretroviral therapyNeurologic complicationsMicroglial activationNeurologic impairmentOpportunistic infectionsClinical studiesEarly initiationNeurocognitive disordersHIV-1Neuropsychological testingHIVNormal agingOngoing abnormalitiesInfectionFurther studiesTherapyComplicationsNeuropathogenesisPoster presentationsAbnormalities
2011
HIV-1 Replication in the Central Nervous System Occurs in Two Distinct Cell Types
Schnell G, Joseph S, Spudich S, Price RW, Swanstrom R. HIV-1 Replication in the Central Nervous System Occurs in Two Distinct Cell Types. PLOS Pathogens 2011, 7: e1002286. PMID: 22007152, PMCID: PMC3188520, DOI: 10.1371/journal.ppat.1002286.Peer-Reviewed Original ResearchConceptsHIV-1-associated dementiaCentral nervous systemHIV-1 populationsMacrophage-tropic virusesCerebrospinal fluidHuman immunodeficiency virus type 1 (HIV-1) infectionNervous systemCSF of subjectsT cell-tropic virusesViral replicationVirus type 1 infectionType 1 infectionHIV-1 replicationHIV-1 variantsHAD subjectsCNS infectionsTherapy initiationCCR5-tropicOvert dementiaVirological characteristicsNeurocognitive disordersHIV-1Virological stateSurface CD4CSF compartmentCentral nervous system complications of HIV infection.
Spudich SS, Ances BM. Central nervous system complications of HIV infection. Topics In Antiviral Medicine 2011, 19: 48-57. PMID: 21868822, PMCID: PMC6148949.Peer-Reviewed Original ResearchConceptsNervous systemCentral nervous system complicationsNervous system complicationsEarly treatment interventionStudy of pathogenesisCentral nervous systemBiomarkers of HANDDisease activityAdjunctive therapyNeurologic injuryHIV infectionOpportunistic infectionsSystem complicationsNeurologic disordersNeurocognitive disordersEtiology of diseaseMeasurable biomarkersEarly infectionTreatment interventionsInfectionHIVBiomarkersDisordersTreatmentNovel molecules
2009
Amyloid and tau cerebrospinal fluid biomarkers in HIV infection
Gisslén M, Krut J, Andreasson U, Blennow K, Cinque P, Brew BJ, Spudich S, Hagberg L, Rosengren L, Price RW, Zetterberg H. Amyloid and tau cerebrospinal fluid biomarkers in HIV infection. BMC Neurology 2009, 9: 63. PMID: 20028512, PMCID: PMC2807422, DOI: 10.1186/1471-2377-9-63.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAIDS Dementia ComplexAIDS-Related Opportunistic InfectionsAlzheimer DiseaseAmyloid beta-PeptidesAmyloid beta-Protein PrecursorAnalysis of VarianceBiomarkersCross-Sectional StudiesFemaleHIV InfectionsHIV-1HumansMaleMiddle AgedPeptide FragmentsPrincipal Component AnalysisTau ProteinsConceptsAIDS dementia complexCerebrospinal fluid biomarkersOpportunistic infectionsADC patientsAlzheimer's diseaseHIV infectionP-tauDisease patientsFluid biomarkersCentral nervous system opportunistic infectionsSoluble amyloid precursor protein alphaLower CSF Aβ1-42CSF t-tau levelsCNS immune activationCNS opportunistic infectionsCSF p-tauCSF t-tauT-tau levelsCross-sectional studyCSF Aβ1-42Alzheimer's disease patientsUninfected subjectsInfection patientsNeural injuryNeurological symptoms