2024
Neurosymptomatic HIV-1 CSF escape is associated with replication in CNS T cells and inflammation
Kincer L, Dravid A, Trunfio M, Calcagno A, Zhou S, Vercesi R, Spudich S, Gisslen M, Price R, Cinque P, Joseph S. Neurosymptomatic HIV-1 CSF escape is associated with replication in CNS T cells and inflammation. Journal Of Clinical Investigation 2024, 134: e176358. PMID: 39352388, PMCID: PMC11444166, DOI: 10.1172/jci176358.Peer-Reviewed Original ResearchConceptsHIV-1 RNACD4+ T cellsHIV-1 populationsAntiretroviral therapyHIV-1T cellsCerebrospinal fluidCSF escapeCNS inflammationDetectable HIV-1 RNAImprovement of neurological symptomsAssociated with viral suppressionUntreated chronic infectionDrug-resistant virusesProgressive neurological deficitsCNS T cellsART regimenViral suppressionChronic infectionNeurological deficitsNeurological symptomsInflammatory biomarkersClinical consequencesVirus expressionPrimary infectionChanges 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 proteomeTranscobalamin receptor antibodies in autoimmune vitamin B12 central deficiency
Pluvinage J, Ngo T, Fouassier C, McDonagh M, Holmes B, Bartley C, Kondapavulur S, Hurabielle C, Bodansky A, Pai V, Hinman S, Aslanpour A, Alvarenga B, Zorn K, Zamecnik C, McCann A, Asencor A, Huynh T, Browne W, Tubati A, Haney M, Douglas V, Louine M, Cree B, Hauser S, Seeley W, Baranzini S, Wells J, Spudich S, Farhadian S, Ramachandran P, Gillum L, Hales C, Zikherman J, Anderson M, Yazdany J, Smith B, Nath A, Suh G, Flanagan E, Green A, Green R, Gelfand J, DeRisi J, Pleasure S, Wilson M. Transcobalamin receptor antibodies in autoimmune vitamin B12 central deficiency. Science Translational Medicine 2024, 16: eadl3758. PMID: 38924428, PMCID: PMC11520464, DOI: 10.1126/scitranslmed.adl3758.Peer-Reviewed Original ResearchConceptsBlood-brain barrierCerebrospinal fluidNeurological deficitsAutoimmune neurological conditionsCohort of patientsCellular uptake of cobalaminVitamin B12B12 transportCerebrospinal fluid samplesMeasurement of vitamin B12Low-density lipoprotein receptorProgrammable phage displayImmunosuppressive treatmentIn vitro modelNeuropsychiatric lupusImmunomodulatory treatmentReceptor antibodiesClinical improvementUptake of cobalaminB12 deficiencyUnknown etiologyHematopoietic cellsTranscobalamin receptorCentral deficiencyB12 supplementationCase-Control Study of Individuals With Small Fiber Neuropathy After COVID-19
McAlpine L, Zubair A, Joseph P, Spudich S. Case-Control Study of Individuals With Small Fiber Neuropathy After COVID-19. Neurology Neuroimmunology & Neuroinflammation 2024, 11: e200244. PMID: 38630952, PMCID: PMC11087026, DOI: 10.1212/nxi.0000000000200244.Peer-Reviewed Original ResearchConceptsInvasive cardiopulmonary exercise testingSmall fiber neuropathyCase-control studyFiber neuropathySkin biopsiesClinical response to treatmentNeurovascular dysregulationTreated with IVIGRetrospective chart reviewCase-control study of individualsRetrospective cohort studyResponse to treatmentCardiopulmonary exercise testingClass III evidenceMyalgic encephalomyelitis/chronic fatigue syndromeIVIG groupClinical responseNeuropathic symptomsChart reviewIVIGStudy of individualsCohort studyIII evidenceClinical trialsCOVID-19 illnessFramingham risk score based vascular outcomes in acute versus chronic HIV cohorts after 6 years of ART
Holroyd K, Han W, Apornpong T, Trautmann L, Gatechompol S, Hiransuthikul A, Ubolyam S, Sacdalan C, Sriplienchan S, Kanaprach R, Kerr S, Avihingsanon A, Spudich S, Chan P. Framingham risk score based vascular outcomes in acute versus chronic HIV cohorts after 6 years of ART. HIV Medicine 2024, 25: 725-736. PMID: 38383057, PMCID: PMC11153003, DOI: 10.1111/hiv.13621.Peer-Reviewed Original ResearchConceptsFramingham risk scoreYears of antiretroviral therapyAcute HIVHigher CD4 countsAntiretroviral therapyChronic HIVCD4 countFollow-upAtherosclerotic cardiovascular diseaseVascular outcomesAssociated with higher body mass indexCardiovascular diseaseRisk scoreHigher body mass indexRisk factorsPrevalence of syphilisVascular agingCD8 T-cell countsMetabolic risk factorsCohort of participantsBody mass indexMultivariate linear regression analysisCardiovascular risk factorsEffect of ART initiationStarted antiretroviral therapy
2023
Antiretroviral Therapy Intensification for Neurocognitive Impairment in Human Immunodeficiency Virus
Letendre S, Chen H, McKhann A, Roa J, Vecchio A, Daar E, Berzins B, Hunt P, Marra C, Campbell T, Coombs R, Ma Q, Swaminathan S, Macatangay B, Morse G, Miller T, Rusin D, Greninger A, Ha B, Alston-Smith B, Robertson K, Paul R, Spudich S, Team T. Antiretroviral Therapy Intensification for Neurocognitive Impairment in Human Immunodeficiency Virus. Clinical Infectious Diseases 2023, 77: 866-874. PMID: 37183889, PMCID: PMC10506779, DOI: 10.1093/cid/ciad265.Peer-Reviewed Original ResearchConceptsAntiretroviral therapyART intensificationNeurocognitive impairmentWeek 48Z-scoreAntiretroviral therapy intensificationPersistent HIV replicationPlacebo-controlled trialPlasma HIV RNASuppressive antiretroviral therapyAge 52 yearsBody mass indexHuman immunodeficiency virusCopies/mLTotal Z-scoreBaseline z-scoresCentral nervous systemDual placeboEfavirenz useTherapy intensificationHIV RNAStudy drugAdverse eventsSymptomatic HIVPrimary outcomeBrain volumetrics differ by Fiebig stage in acute HIV infection
Bolzenius J, Sacdalan C, Ndhlovu L, Sailasuta N, Trautmann L, Tipsuk S, Crowell T, Suttichom D, Colby D, Phanuphak N, Chan P, Premeaux T, Kroon E, Vasan S, Hsu D, Valcour V, Ananworanich J, Robb M, Ake J, Pohl K, Sriplienchan S, Spudich S, Paul R. Brain volumetrics differ by Fiebig stage in acute HIV infection. AIDS 2023, 37: 861-869. PMID: 36723491, PMCID: PMC10079583, DOI: 10.1097/qad.0000000000003496.Peer-Reviewed Original ResearchConceptsAcute HIV infectionNucleus accumbensFiebig stagesAcute infectionHIV infectionCaudate nucleusBrain volumeLower regional brain volumesAntiretroviral therapy initiationMarkers of neuroinflammationBrain volume alterationsCross-sectional studyRegional brain volumesT1-weighted scansTherapy initiationChronic infectionBrain volumetricsBrain disruptionThai malesViral factorsPutamenVolume alterationsAccumbensInfectionStimulant use
2021
VZV myelitis with secondary HIV CSF escape
Weiss JJ, Spudich S, Barakat L. VZV myelitis with secondary HIV CSF escape. BMJ Case Reports 2021, 14: e241738. PMID: 34187795, PMCID: PMC8245447, DOI: 10.1136/bcr-2021-241738.Peer-Reviewed Case Reports and Technical NotesConceptsVaricella-zoster virusCSF escapeVZV myelitisSkin lesionsCerebrospinal fluidCSF HIV viral loadRight upper extremity weaknessCentral nervous system infectionSubsequent oral therapyUpper extremity weaknessHIV viral loadNervous system infectionVesicular skin lesionsCopies/mLDirect fluorescent antibody testingFluorescent antibody testingIntravenous acyclovirVZV PCRExtremity weaknessOral therapyRare complicationSystem infectionAtypical presentationImmunosuppressed patientsVZV infectionCompartmentalization 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 responseIschemic Stroke, Inflammation, and Endotheliopathy in COVID-19 Patients
McAlpine LS, Zubair AS, Maran I, Chojecka P, Lleva P, Jasne AS, Navaratnam D, Matouk C, Schindler J, Sheth KN, Chun H, Lee AI, Spudich S, Sharma R, Sansing LH. Ischemic Stroke, Inflammation, and Endotheliopathy in COVID-19 Patients. Stroke 2021, 52: e233-e238. PMID: 33966492, PMCID: PMC8140646, DOI: 10.1161/strokeaha.120.031971.Peer-Reviewed Original Research
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 HIVSelective 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 provirusesInflammationTherapyProvirusStroke Code Presentations, Interventions, and Outcomes Before and During the COVID-19 Pandemic
Jasne AS, Chojecka P, Maran I, Mageid R, Eldokmak M, Zhang Q, Nystrom K, Vlieks K, Askenase M, Petersen N, Falcone GJ, Wira CR, Lleva P, Zeevi N, Narula R, Amin H, Navaratnam D, Loomis C, Hwang DY, Schindler J, Hebert R, Matouk C, Krumholz HM, Spudich S, Sheth KN, Sansing LH, Sharma R. Stroke Code Presentations, Interventions, and Outcomes Before and During the COVID-19 Pandemic. Stroke 2020, 51: 2664-2673. PMID: 32755347, PMCID: PMC7446978, DOI: 10.1161/str.0000000000000347.Peer-Reviewed Original ResearchMeSH KeywordsAgedAged, 80 and overBetacoronavirusBrain IschemiaCohort StudiesComorbidityConnecticutCoronary Artery DiseaseCoronavirus InfectionsCOVID-19DyslipidemiasEmergency Medical ServicesEthnicityFemaleHumansHypertensionIncomeInsurance, HealthIntracranial HemorrhagesMaleMedically UninsuredMiddle AgedOutcome and Process Assessment, Health CarePandemicsPneumonia, ViralRetrospective StudiesSARS-CoV-2Severity of Illness IndexStrokeSubstance-Related DisordersTelemedicineThrombectomyThrombolytic TherapyTime-to-TreatmentConceptsComprehensive stroke centerStroke codePatient characteristicsStroke severityStroke code patientsHistory of hypertensionStroke-like symptomsCoronary artery diseaseCoronavirus disease 2019 (COVID-19) pandemicPatient-level dataLower median household incomePublic health initiativesDisease 2019 pandemicCOVID-19 pandemicRace/ethnicityCode patientsHospital presentationPublic health insuranceRankin ScaleStroke centersArtery diseaseReperfusion timeStroke symptomsEarly outcomesConnecticut hospitals
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 pathwaysDysfunctionTherapyPersistent HIV-infected cells in cerebrospinal fluid are associated with poorer neurocognitive performance
Spudich S, Robertson KR, Bosch RJ, Gandhi RT, Cyktor JC, Mar H, Macatangay BJ, Lalama CM, Rinaldo C, Collier AC, Godfrey C, Eron JJ, McMahon D, Jacobs JL, Koontz D, Hogg E, Vecchio A, Mellors JW. Persistent HIV-infected cells in cerebrospinal fluid are associated with poorer neurocognitive performance. Journal Of Clinical Investigation 2019, 129: 3339-3346. PMID: 31305262, PMCID: PMC6668666, DOI: 10.1172/jci127413.Peer-Reviewed Original ResearchConceptsLong-term antiretroviral therapyPeripheral blood mononuclear cellsAntiretroviral therapyHIV RNACerebrospinal fluidPoorer neurocognitive performanceInflammatory biomarkersNeurocognitive performanceCell-associated HIV DNACell-free HIV RNAHigher plasma HIV RNAYears of ARTCSF HIV RNACSF inflammatory biomarkersWorse neurocognitive outcomesNadir CD4 countPlasma HIV RNABlood mononuclear cellsQuantitative PCRGlobal deficit scoreHalf of individualsCell-free RNACSF supernatantHIV persistenceCD4 countSwitch to dolutegravir is well tolerated in Thais with HIV infection
Goh OQ, Colby DJ, Pinyakorn S, Sacdalan C, Kroon E, Chan P, Chomchey N, Kanaprach R, Prueksakaew P, Suttichom D, Trichavaroj R, Spudich S, Robb ML, Phanuphak P, Phanuphak N, Ananworanich J, Group O. Switch to dolutegravir is well tolerated in Thais with HIV infection. Journal Of The International AIDS Society 2019, 22: e25324. PMID: 31294931, PMCID: PMC6621926, DOI: 10.1002/jia2.25324.Peer-Reviewed Original ResearchConceptsAcute HIV infectionBody mass indexIncident hepatitis C virus infectionHepatitis C virus infectionC virus infectionAdverse eventsAntiretroviral therapyHIV infectionVirus infectionFirst-line antiretroviral therapyHepatitis C virus coinfectionLiver-related adverse eventsLower body mass indexC virus coinfectionDTG-based regimensOnly risk factorMedian body weightPossible adverse eventsHepatitis C virusAbacavir therapyLaboratory abnormalitiesMedian ageVirus coinfectionMass indexNeuropsychiatric symptomsPredicting Efavirenz Concentrations in the Brain Tissue of HIV‐Infected Individuals and Exploring their Relationship to Neurocognitive Impairment
Srinivas N, Joseph SB, Robertson K, Kincer LP, Menezes P, Adamson L, Schauer AP, Blake KH, White N, Sykes C, Luciw P, Eron JJ, Forrest A, Price R, Spudich S, Swanstrom R, Kashuba A. Predicting Efavirenz Concentrations in the Brain Tissue of HIV‐Infected Individuals and Exploring their Relationship to Neurocognitive Impairment. Clinical And Translational Science 2019, 12: 302-311. PMID: 30675981, PMCID: PMC6510381, DOI: 10.1111/cts.12620.Peer-Reviewed Original ResearchConceptsBrain tissue concentrationsCerebrospinal fluidBrain tissueRhesus macaquesNeurocognitive scoresPK/pharmacodynamic analysesPenetration of antiretroviralsTissue concentrationsExposure-response analysisConcentration-time curveAdult rhesus macaquesCSF AUCEfavirenz concentrationsPlasma AUCPharmacodynamic analysisClinical studiesTissue AUCNeurocognitive impairmentCSF samplesPharmacokinetic dataPK modelingHIVTime pointsAUCNecropsyCerebrospinal 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
Human Immunodeficiency Virus Type 1 RNA Detected in the Central Nervous System (CNS) After Years of Suppressive Antiretroviral Therapy Can Originate from a Replicating CNS Reservoir or Clonally Expanded Cells
Joseph SB, Kincer LP, Bowman NM, Evans C, Vinikoor MJ, Lippincott CK, Gisslén M, Spudich S, Menezes P, Robertson K, Archin N, Kashuba A, Eron JJ, Price RW, Swanstrom R. Human Immunodeficiency Virus Type 1 RNA Detected in the Central Nervous System (CNS) After Years of Suppressive Antiretroviral Therapy Can Originate from a Replicating CNS Reservoir or Clonally Expanded Cells. Clinical Infectious Diseases 2018, 69: 1345-1352. PMID: 30561541, PMCID: PMC6938202, DOI: 10.1093/cid/ciy1066.Peer-Reviewed Original ResearchConceptsCentral nervous systemHIV-1 RNA concentrationsAntiretroviral therapySuppressive antiretroviral therapyCerebrospinal fluidCNS reservoirsCSF escapeCSF HIV-1 RNA concentrationsCentral nervous system reservoirYears of ARTHuman immunodeficiency virus type 1 (HIV-1) populationHuman immunodeficiency virus type 1 (HIV-1) RNAStable antiretroviral therapyHIV-1 RNAMacrophages/microgliaInfected T cellsRNA concentrationViral envelope sequencesType 1 populationViral populationsViral suppressionMacrophage-tropicAsymptomatic participantsMultiple time pointsT cellsCSF 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