2024
Central 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 Original ResearchMeSH 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 initiationHIV-1–infected T cell clones are shared across cerebrospinal fluid and blood during ART
Wang M, Yoon J, Reisert H, Das B, Orlinick B, Chiarella J, Halvas E, Mellors J, Pang A, Barakat L, Fikrig M, Cyktor J, Kluger Y, Spudich S, Corley M, Farhadian S. HIV-1–infected T cell clones are shared across cerebrospinal fluid and blood during ART. JCI Insight 2024, 9: e176208. PMID: 38587074, PMCID: PMC11128194, DOI: 10.1172/jci.insight.176208.Peer-Reviewed Original ResearchConceptsT cell clonesT cell receptorCerebrospinal fluidT cellsHIV-1Infected T-cell clonesCentral memory T cellsCD4 T-cell clonesDetectable HIV RNAMemory T cellsHIV-1 RNAInfected T cellsCNS reservoirsHIV persistenceHIV reservoirHIV RNAHIV cureReservoir cellsPWHTissue compartmentsBloodCNSUninfected controlsCD4Infected cells
2023
Biotypes of Central Nervous System Complications in People With Human Immunodeficiency Virus: Virology, Immunology, and Neuropathology
Joseph S, Gianella S, Burdo T, Cinque P, Gisslen M, Letendre S, Nath A, Morgello S, Ndhlovu L, Spudich S. Biotypes of Central Nervous System Complications in People With Human Immunodeficiency Virus: Virology, Immunology, and Neuropathology. The Journal Of Infectious Diseases 2023, 227: s3-s15. PMID: 36930640, PMCID: PMC10022721, DOI: 10.1093/infdis/jiac370.Peer-Reviewed Original ResearchMeSH KeywordsCentral Nervous SystemCentral Nervous System DiseasesCognitive DysfunctionHIV InfectionsHIV-1HumansConceptsHuman immunodeficiency virusCentral nervous system complicationsNervous system complicationsAntiretroviral therapySystem complicationsImmunodeficiency virusMental health disordersMild cognitive impairmentCNS complicationsMultifactorial pathogenesisViral suppressionHeterogeneity of mechanismsCNS diseaseNeuropathological dataEffective treatmentHealth disordersCognitive impairmentPreventive interventionsComplicationsImmunologyVirusWorking GroupVirologyNeuroHIVNeuropathologyRebound 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 influxVirus
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 consequencesBrainNeuropathogenesisHIV Compartmentalization in the CNS and Its Impact in Treatment Outcomes and Cure Strategies
Chan P, Spudich S. HIV Compartmentalization in the CNS and Its Impact in Treatment Outcomes and Cure Strategies. Current HIV/AIDS Reports 2022, 19: 207-216. PMID: 35536438, PMCID: PMC10590959, DOI: 10.1007/s11904-022-00605-1.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsMeSH KeywordsCentral Nervous SystemHIV InfectionsHIV SeropositivityHIV-1HumansRNA, ViralTreatment OutcomeViral LoadConceptsHIV-1 escapeAntiretroviral therapyCentral nervous system reservoirHIV-1 infection resultsStable antiretroviral therapyCerebrospinal fluid findingsWorse neurocognitive performanceTreatment interruption studiesHIV compartmentalizationCNS reservoirsCure strategiesChronic infectionTreatment outcomesCells persistRecent FindingsComparedInfection resultsReviewThis reviewViral variantsViral replicationSummaryFuture studiesNeurocognitive performanceInterruption studiesSystemic reservoirInfected cellsLongitudinal benefits
2021
Cerebrospinal fluid CD4+ T cell infection in humans and macaques during acute HIV-1 and SHIV infection
Sharma V, Creegan M, Tokarev A, Hsu D, Slike BM, Sacdalan C, Chan P, Spudich S, Ananworanich J, Eller MA, Krebs SJ, Vasan S, Bolton DL. Cerebrospinal fluid CD4+ T cell infection in humans and macaques during acute HIV-1 and SHIV infection. PLOS Pathogens 2021, 17: e1010105. PMID: 34874976, PMCID: PMC8683024, DOI: 10.1371/journal.ppat.1010105.Peer-Reviewed Original ResearchConceptsT-cell infectionCentral nervous systemAcute HIV-1HIV-1 replicationCerebrospinal fluidT cellsHIV-1Peripheral bloodViral reservoirCell infectionBroad immune activationCerebrospinal fluid CD4CNS viral reservoirCSF T cellsHIV-1 cureActive viral transcriptionLong-term inflammationViral RNACSF CD4Early neuroinflammationAntiretroviral therapyHuman cerebrospinal fluidAcute infectionImmune activationCNS compartmentCompartmentalization 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
Central Nervous System Safety During Brief Analytic Treatment Interruption of Antiretroviral Therapy Within 4 Human Immunodeficiency Virus Remission Trials: An Observational Study in Acutely Treated People Living With Human Immunodeficiency Virus
Hellmuth J, Muccini C, Colby DJ, Kroon E, de Souza M, Crowell TA, Chan P, Sacdalan C, Intasan J, Benjapornpong K, Tipsuk S, Puttamaswin S, Chomchey N, Valcour V, Sarnecki M, Tomaka F, Krebs SJ, Slike BM, Jagodzinski LL, Dumrongpisutikul N, Sailasuta N, Samboju V, Michael NL, Robb ML, Vasan S, Ananworanich J, Phanuphak P, Phanuphak N, Paul R, Spudich S. Central Nervous System Safety During Brief Analytic Treatment Interruption of Antiretroviral Therapy Within 4 Human Immunodeficiency Virus Remission Trials: An Observational Study in Acutely Treated People Living With Human Immunodeficiency Virus. Clinical Infectious Diseases 2020, 73: e1885-e1892. PMID: 32916708, PMCID: PMC8492357, DOI: 10.1093/cid/ciaa1344.Peer-Reviewed Original ResearchMeSH KeywordsAdultAnti-Retroviral AgentsCentral Nervous SystemDiffusion Tensor ImagingHIVHIV InfectionsHumansMaleViral LoadConceptsAnalytic treatment interruptionHuman immunodeficiency virusAntiretroviral therapyCentral nervous systemRemission trialsDiffusion tensor imagingTreatment interruptionMedian timeImmunodeficiency virusCentral nervous system safetyCSF HIV-1 RNAAdverse CNS effectsAcute HIV infectionImmune activation markersPlasma viral loadHIV-1 RNAMedian participant ageCerebrospinal fluid samplingCognitive performanceHIV remission trialsBrain diffusion tensor imagingMagnetic resonance spectroscopyART resumptionCNS safetyMild worsening
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 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 diseases
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 cellsSingle-cell RNA sequencing reveals microglia-like cells in cerebrospinal fluid during virologically suppressed HIV
Farhadian SF, Mehta SS, Zografou C, Robertson K, Price RW, Pappalardo J, Chiarella J, Hafler DA, Spudich SS. Single-cell RNA sequencing reveals microglia-like cells in cerebrospinal fluid during virologically suppressed HIV. JCI Insight 2018, 3: e121718. PMID: 30232286, PMCID: PMC6237230, DOI: 10.1172/jci.insight.121718.Peer-Reviewed Original ResearchConceptsCerebrospinal fluidHIV infectionImmune activationAntiretroviral therapyNeuronal injuryCentral nervous system immune activationLong-term suppressive antiretroviral therapySingle-cell RNA sequencingCNS immune activationDisease-associated microgliaSuppressive antiretroviral therapyImmune cell subsetsMicroglia-like cellsGene expression signaturesNeuronal damageNeuroinflammatory diseasesRNA sequencingCell subsetsCNS cellsNeurological conditionsRare subsetNeurocognitive impairmentMyeloid cellsCellular subsetsInfectionNormalization of Soluble CD163 Levels After Institution of Antiretroviral Therapy During Acute HIV Infection Tracks with Fewer Neurological Abnormalities
D’Antoni M, Byron MM, Chan P, Sailasuta N, Sacdalan C, Sithinamsuwan P, Tipsuk S, Pinyakorn S, Kroon E, Slike BM, Krebs SJ, Khadka VS, Chalermchai T, Kallianpur KJ, Robb M, Spudich S, Valcour V, Ananworanich J, Ndhlovu LC, Teeratakulpisarn N, Fletcher J, Sacdalan C, Chomchey N, Sutthichom D, Rattanamanee S, Prueksakaew P, Ubolyam S, Eamyoung P, Puttamaswin S, Karnsomlap P, Luekasemsuk T, Intasan J, Benjapornpong K, Ratnaratorn N, O’Connell R, Trichavaroj R, Akapirat S, Phuang-Ngern Y, Sukhumvittaya S, Sajjaweerawan C, Jongrakthaitae S, Saetun P, Tragonlugsana N, Nuntapinit B, Tantibul N, Savadsuk H, Michael N, Trautmann L, Tovanabutra S, Ouellette M, Butterworth O, Crowell T, Turk E, Eller L, Milazzo M, Bandar I, Shiramizu B, Shikuma C. Normalization of Soluble CD163 Levels After Institution of Antiretroviral Therapy During Acute HIV Infection Tracks with Fewer Neurological Abnormalities. The Journal Of Infectious Diseases 2018, 218: 1453-1463. PMID: 29868826, PMCID: PMC6151077, DOI: 10.1093/infdis/jiy337.Peer-Reviewed Original ResearchConceptsAcute HIV infectionFiebig stage IIIStage I/IISoluble CD163 levelsHIV infectionCentral nervous systemStage IIICD163 levelsCerebrospinal fluidUninfected controlsChronic human immunodeficiency virus (HIV) infectionCombination antiretroviral therapy (cART) initiationHuman immunodeficiency virus (HIV) infectionInitiation of cARTAntiretroviral therapy initiationImmunodeficiency virus infectionEnzyme-linked immunosorbentCART initiationMyeloid activationAntiretroviral therapyChronic HIVCNS involvementSCD163 levelsTherapy initiationActivation markersDistribution of Human Immunodeficiency Virus (HIV) Ribonucleic Acid in Cerebrospinal Fluid and Blood Is Linked to CD4/CD8 Ratio During Acute HIV
Chan P, Patel P, Hellmuth J, Colby DJ, Kroon E, Sacdalan C, Pinyakorn S, Jagodzinski L, Krebs S, Ananworanich J, Valcour V, Spudich S, Team R. Distribution of Human Immunodeficiency Virus (HIV) Ribonucleic Acid in Cerebrospinal Fluid and Blood Is Linked to CD4/CD8 Ratio During Acute HIV. The Journal Of Infectious Diseases 2018, 218: 937-945. PMID: 29741638, PMCID: PMC6093332, DOI: 10.1093/infdis/jiy260.Peer-Reviewed Original ResearchMeSH KeywordsAcute DiseaseAdultCD4-CD8 RatioCentral Nervous SystemFemaleHIVHIV InfectionsHumansMaleRNA, ViralThailandVirus InternalizationYoung AdultConceptsCD4/CD8 ratioCSF HIV RNAHIV RNACD8 ratioCerebrospinal fluidHIV infectionHuman immunodeficiency virus ribonucleic acidCerebrospinal fluid (CSF) immune markersLog10 copies/mLStage I/IIHuman immunodeficiency virus (HIV) RNAChronic HIV infectionHigher CSF neopterinAcute HIV infectionPlasma HIV RNACopies/mLHuman immunodeficiency virus ribonucleic acid levelsRibonucleic acid levelsVirus ribonucleic acidAcute HIVCSF neopterinSCD14 levelsAcute infectionMedian ageImmune markers
2017
CROI 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 changesInfectionImpairmentImmune activation in the central nervous system throughout the course of HIV infection
Spudich SS. Immune activation in the central nervous system throughout the course of HIV infection. Current Opinion In HIV And AIDS 2016, 11: 226-233. PMID: 26760827, PMCID: PMC4773903, DOI: 10.1097/coh.0000000000000243.Peer-Reviewed Original ResearchConceptsCombination antiretroviral therapyImmune activationAntiretroviral therapySuppressive combination antiretroviral therapyLong-term neurologic sequelaeCentral nervous system responseCNS immune activationFeatures of homeostasisPersistent immune activationBrain microglial cellsCervical lymph nodesCentral nervous systemSustained immune responseNervous system responsesImmune surveillance networkNeurologic sequelaeAcute infectionHIV infectionLymph nodesActivation associatesMicroglial cellsChronic infectionCNS cellsImmune responseCerebrospinal fluid
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 subjectsCerebral white matter integrity during primary HIV infection
Wright PW, Vaida FF, Fernández R, Rutlin J, Price RW, Lee E, Peterson J, Fuchs D, Shimony JS, Robertson KR, Walter R, Meyerhoff DJ, Spudich S, Ances BM. Cerebral white matter integrity during primary HIV infection. AIDS 2015, 29: 433-442. PMID: 25513818, PMCID: PMC4916955, DOI: 10.1097/qad.0000000000000560.Peer-Reviewed Original ResearchMeSH KeywordsAdultAnti-HIV AgentsBiomarkersBlood-Brain BarrierCD4 Lymphocyte CountCD4-Positive T-LymphocytesCentral Nervous SystemCorpus CallosumCross-Sectional StudiesDiffusion Tensor ImagingHIV InfectionsHIV-1HumansInflammationMaleNeuropsychological TestsProspective StudiesRNA, ViralViral LoadWhite MatterConceptsPrimary HIV infectionLog10 copies/Diffusion tensor imagingBlood-brain barrierHIV infectionWhite matter integrityCopies/Cerebrospinal fluidHIV-1 RNA viral loadMedian CD4 cell countCross-sectional neuroimaging studiesDTI metricsChronic HIV infectionHIV-uninfected (HIV−) participantsDTI measuresCD4 cell countRNA viral loadWhole-brain voxelwise analysisEarly HIV infectionWhite matter involvementBiomarkers of infectionDuration of infectionCentral nervous systemWhite matter microstructural integrityCerebral white matter integrity