2023
Rebound HIV-1 in cerebrospinal fluid after antiviral therapy interruption is mainly clonally amplified R5 T cell-tropic virus
Kincer L, Joseph S, Gilleece M, Hauser B, Sizemore S, Zhou S, Di Germanio C, Zetterberg H, Fuchs D, Deeks S, Spudich S, Gisslen M, Price R, Swanstrom R. Rebound HIV-1 in cerebrospinal fluid after antiviral therapy interruption is mainly clonally amplified R5 T cell-tropic virus. Nature Microbiology 2023, 8: 260-271. PMID: 36717718, PMCID: PMC10201410, DOI: 10.1038/s41564-022-01306-6.Peer-Reviewed Original ResearchConceptsCentral nervous systemT cell-tropic virusesInfected T cellsCerebrospinal fluidAntiretroviral therapyHIV-1Rebound virusViral loadT cellsMacrophage-tropic HIV-1CSF viral loadSuppressive antiretroviral therapyHIV-1 reservoirMacrophage-tropic virusesHigh viral loadWhite blood cellsTherapy interruptionLatent reservoirLymphoid systemNervous systemSystemic infectionVirus replicationBlood cellsTransient influxVirusHIV-1 is Transported into the Central Nervous System by Trafficking Infected Cells
Kincer L, Schnell G, Swanstrom R, Miller M, Spudich S, Eron J, Price R, Joseph S. HIV-1 is Transported into the Central Nervous System by Trafficking Infected Cells. Pathogens And Immunity 2023, 7: 131-142. PMID: 36865569, PMCID: PMC9973728, DOI: 10.20411/pai.v7i2.524.Peer-Reviewed Original ResearchBlood-cerebrospinal fluid barrierBlood-brain barrierCentral nervous systemHIV-1Cerebrospinal fluidInfected cellsCSF samplesNervous systemCo-infected participantsHCV viral loadHIV-1 replicationCross-sectional studyMigration of HIVHIV-1 particlesHIV-1 populationsBlood plasmaHCV concentrationAntiviral regimensViral loadHCV entryInflammatory responseFluid barrierHCVVirus entryNormal surveillance
2022
Neuropathogenesis 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 consequencesBrainNeuropathogenesis
2021
Chapter 43 HIV and Other Retroviral Infections of the Nervous System
Peluso M, Spudich S. Chapter 43 HIV and Other Retroviral Infections of the Nervous System. 2021, 765-784. DOI: 10.1016/b978-0-12-819306-8.00043-5.Peer-Reviewed Original ResearchAntiretroviral therapyHIV infectionNeurologic manifestationsHuman immunodeficiency virus (HIV) infectionEra of ARTSuccessful systemic treatmentImmunodeficiency virus infectionEarly HIV infectionSystemic immune systemQuality of lifeAdvanced immunosuppressionAntiretroviral statusNeurologic complicationsNeurologic presentationSystemic treatmentVirus infectionCNS effectsCognitive disordersNervous systemImmune systemInfectionRetroviral infectionComplicationsHIVTherapy
2020
Neuropathogenesis and Neurologic Manifestations of the Coronaviruses in the Age of Coronavirus Disease 2019
Zubair AS, McAlpine LS, Gardin T, Farhadian S, Kuruvilla DE, Spudich S. Neuropathogenesis and Neurologic Manifestations of the Coronaviruses in the Age of Coronavirus Disease 2019. JAMA Neurology 2020, 77: 1018-1027. PMID: 32469387, PMCID: PMC7484225, DOI: 10.1001/jamaneurol.2020.2065.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsCentral nervous systemCoronavirus disease 2019Nervous systemDisease 2019Respiratory syndromeCOVID-19Severe acute respiratory syndrome coronavirus 2Acute respiratory syndrome coronavirus 2Long-term neurologic sequelaeRespiratory syndrome coronavirus 2Middle East respiratory syndromeSevere acute respiratory syndromeClinical neurological complicationsFurther neuropathological studiesBest treatment algorithmImproved clinical outcomesBlood-brain barrierImpairment of consciousnessSyndrome coronavirus 2Peripheral nervous systemAcute respiratory syndromeHuman coronavirus disease 2019Common neurologic complaintsSARS-CoV-2Neurologic sequelae
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 pathwaysDysfunctionTherapyHIV 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 ResearchPotential 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
2017
HIV-Associated Neurocognitive Disorders
Letendre S, Iudicello J, Ances B, Marcotte T, Spudich S, Cohen M. HIV-Associated Neurocognitive Disorders. 2017, 175-203. DOI: 10.1093/med/9780199392742.003.0016.Peer-Reviewed Original ResearchHIV-associated neurocognitive disordersHuman immunodeficiency virusDifferential diagnosis of cognitive impairmentNeurocognitive disordersDifferential diagnosisDiagnosis of cognitive impairmentHuman immunodeficiency virus patientsCognitive impairmentInitiation of ARTLoss of dendritesCentral nervous systemSubstance use disordersInfected gliaImmunodeficiency virusMedication toxicityInjured neuronsMetabolic syndromeTissue macrophagesTreatment recommendationsInfluence neurocognitive performanceQuality of lifeNeurocognitive performanceVascular diseaseNervous systemMultimorbid conditionsCROI 2017: Neurologic Complications of HIV Infection.
Spudich SS, Ances BM. CROI 2017: Neurologic Complications of HIV Infection. Topics In Antiviral Medicine 2017, 25: 69-76. PMID: 28598791, PMCID: PMC5677044.Peer-Reviewed Original ResearchConceptsEarly HIV infectionHIV infectionCentral nervous systemAntiretroviral therapyCNS HIV infectionPotential viral reservoirAntiretroviral regimensSuppressive therapyVirologic controlNeurologic complicationsBrain macrophagesOpportunistic infectionsViral reservoirCognitive screening testsMicroglial cellsChronic infectionRisk factorsNeurocognitive disordersT cellsChoroid plexusNervous systemCognitive impairmentNumerous cohortsScreening testLongitudinal evaluation
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 changesInfectionImpairment
2015
Phenotypic Correlates of HIV-1 Macrophage Tropism
Arrildt KT, LaBranche CC, Joseph SB, Dukhovlinova EN, Graham WD, Ping LH, Schnell G, Sturdevant CB, Kincer LP, Mallewa M, Heyderman RS, Van Rie A, Cohen MS, Spudich S, Price RW, Montefiori DC, Swanstrom R. Phenotypic Correlates of HIV-1 Macrophage Tropism. Journal Of Virology 2015, 89: 11294-11311. PMID: 26339058, PMCID: PMC4645658, DOI: 10.1128/jvi.00946-15.Peer-Reviewed Original ResearchMeSH KeywordsAntibodies, MonoclonalAntibodies, NeutralizingAntibodies, ViralCD4 AntigensCD4-Positive T-LymphocytesCell Line, TumorHEK293 CellsHIV Envelope Protein gp120HIV Envelope Protein gp160HIV Envelope Protein gp41HIV InfectionsHIV-1HumansMacrophagesReceptors, CCR5Recombinant ProteinsViral TropismVirus InternalizationConceptsT cell-tropic virusesT-tropic virusesMonocyte-derived macrophagesM-tropic virusesMacrophage-tropic virusesV1/V2 regionSoluble CD4Central nervous systemHIV-1Chronic infectionT cellsMacrophage-tropic HIV-1 variantsNervous systemM-tropic HIV-1HIV-1 env geneEnv proteinV2 regionT-cell tropicHIV-1 variantsCD4-bound conformationMacrophage-tropicMacrophage tropismM-tropicSurface CD4CD4CNS reservoirs for HIV: implications for eradication
Hellmuth J, Valcour V, Spudich S. CNS reservoirs for HIV: implications for eradication. Journal Of Virus Eradication 2015, 1: 67-71. PMID: 26430703, PMCID: PMC4586130, DOI: 10.1016/s2055-6640(20)30489-1.Peer-Reviewed Original ResearchCompartmentalized 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 ResearchConceptsCentral 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 stageHIVCROI 2015: Neurologic Complications of HIV Infection.
Spudich SS, Ances BM. CROI 2015: Neurologic Complications of HIV Infection. Topics In Antiviral Medicine 2015, 23: 47-55. PMID: 25965311, PMCID: PMC6148901.Peer-Reviewed Original ResearchConceptsCentral nervous systemModifiable risk factorsPathogenesis of HIVQuality of lifeBiomarkers of HANDResource-limited settingsNeurologic complicationsNeurologic presentationHIV infectionCNS reservoirsOpportunistic infectionsRisk factorsHIV epidemicCNS disordersCognitive dysfunctionNeurocognitive disordersHIVNervous systemInfectionDisordersCollaborative studyComplicationsDysfunctionPathogenesisDiagnosis
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 ResearchConceptsCentral 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 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 mediatorsEvolving Character of Chronic Central Nervous System HIV Infection
Price RW, Spudich SS, Peterson J, Joseph S, Fuchs D, Zetterberg H, Gisslén M, Swanstrom R. Evolving Character of Chronic Central Nervous System HIV Infection. Seminars In Neurology 2014, 34: 007-013. PMID: 24715483, PMCID: PMC4120280, DOI: 10.1055/s-0034-1372337.Peer-Reviewed Original ResearchConceptsAntiretroviral therapyCentral nervous systemHuman immunodeficiency virus type 1 (HIV-1) infectionCentral nervous system HIV infectionSystemic infectionVirus type 1 infectionCombination antiretroviral therapyType 1 infectionResource-poor settingsUntreated courseCNS infectionsHIV infectionClinical presentationMotor dysfunctionCNS injuryInflammatory responseNervous systemViral pathogenesisInfectionCharacteristic cognitiveDysfunctionBroad prevalenceHADMarked declineSevere consequences