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 infection
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 ResearchConceptsHuman 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 GroupVirologyNeuroHIVNeuropathology
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 viral transcription and immune perturbations in the CNS of people with HIV despite ART
Farhadian SF, Lindenbaum O, Zhao J, Corley MJ, Im Y, Walsh H, Vecchio A, Garcia-Milian R, Chiarella J, Chintanaphol M, Calvi R, Wang G, Ndhlovu LC, Yoon J, Trotta D, Ma S, Kluger Y, Spudich S. HIV viral transcription and immune perturbations in the CNS of people with HIV despite ART. JCI Insight 2022, 7: e160267. PMID: 35801589, PMCID: PMC9310520, DOI: 10.1172/jci.insight.160267.Peer-Reviewed Original ResearchConceptsCerebrospinal fluidHIV infectionHIV-1-infected cellsCNS viral persistenceCentral memory CD4T-cell abnormalitiesHIV-1 RNAMicroglia-like cellsT cell activationSystemic viral suppressionAbnormal CD8HIV neuropathogenesisViral suppressionMemory CD4CNS reservoirsImmune perturbationsExperience elevated ratesNeuroimmune effectsPeripheral bloodNeurological impairmentViral persistenceT cellsCell abnormalitiesUninfected controlsCell activationImmunological, 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 infectionSingle-cell multiomics reveals persistence of HIV-1 in expanded cytotoxic T cell clones
Collora JA, Liu R, Pinto-Santini D, Ravindra N, Ganoza C, Lama JR, Alfaro R, Chiarella J, Spudich S, Mounzer K, Tebas P, Montaner LJ, van Dijk D, Duerr A, Ho YC. Single-cell multiomics reveals persistence of HIV-1 in expanded cytotoxic T cell clones. Immunity 2022, 55: 1013-1031.e7. PMID: 35320704, PMCID: PMC9203927, DOI: 10.1016/j.immuni.2022.03.004.Peer-Reviewed Original ResearchConceptsHIV-1 eradicationHIV-1 RNAHIV-1Effector memory Th1 cellsHIV-1-infected individualsHIV-1-infected CD4Clonal expansionCell clonesMemory Th1 cellsCell clonal expansionPersistent antigenAntiretroviral therapyViral suppressionCytotoxic CD4Cytotoxic TTh1 cellsAntigen stimulationClonal expansion dynamicsUninfected individualsSurface protein expressionTNF responseUnstimulated conditionsTCR sequencesProtein expressionCD4
2021
Preliminary In Vivo Evidence of Reduced Synaptic Density in Human Immunodeficiency Virus (HIV) Despite Antiretroviral Therapy
Weiss JJ, Calvi R, Naganawa M, Toyonaga T, Farhadian SF, Chintanaphol M, Chiarella J, Zheng MQ, Ropchan J, Huang Y, Pietrzak RH, Carson RE, Spudich S. Preliminary In Vivo Evidence of Reduced Synaptic Density in Human Immunodeficiency Virus (HIV) Despite Antiretroviral Therapy. Clinical Infectious Diseases 2021, 73: 1404-1411. PMID: 34050746, PMCID: PMC8528400, DOI: 10.1093/cid/ciab484.Peer-Reviewed Original ResearchConceptsHuman immunodeficiency virusAntiretroviral therapySynaptic densityMagnetic resonance imagingMale PLWHImmunodeficiency virusUnderwent magnetic resonance imagingPositron emission tomographicCross-sectional pilotHIV neuropathogenesisViral suppressionCommon complicationSynaptic injuryNeurological impairmentDynamic biomarkersPLWHTherapeutic studiesCortical areasMotor coordinationPathological hallmarkPET scanningPromising biomarkerTherapeutic interventionsResonance imagingPegboard performanceCompartmentalization 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 responseCognitive 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
Neuropsychiatric outcomes before and after switching to dolutegravir-based therapy in an acute HIV cohort
Chan P, Goh O, Kroon E, Colby D, Sacdalan C, Pinyakorn S, Prueksakaew P, Reiss P, Ananworanich J, Valcour V, Spudich S, Paul R. Neuropsychiatric outcomes before and after switching to dolutegravir-based therapy in an acute HIV cohort. AIDS Research And Therapy 2020, 17: 1. PMID: 31907064, PMCID: PMC6945418, DOI: 10.1186/s12981-019-0257-8.Peer-Reviewed Original ResearchConceptsPatient Health Questionnaire-9Acute HIV infectionWeeks of ARTAntiretroviral therapyPHQ-9 scoresDTG-based antiretroviral therapyLower PHQ-9 scoresDolutegravir-based therapyDTG-based regimenNeuropsychiatric adverse eventsPlasma viral suppressionFirst-line treatmentPre-existing depressionLeast moderate depressionModerate-severe depressionModerate depression symptomsPercentage of participantsDTG useViral suppressionHIV cohortMedian durationAdverse eventsHIV infectionHighest quartileMultivariable analysis
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 pathwaysDysfunctionTherapyRecommendations for analytical antiretroviral treatment interruptions in HIV research trials—report of a consensus meeting
Julg B, Dee L, Ananworanich J, Barouch DH, Bar K, Caskey M, Colby DJ, Dawson L, Dong KL, Dubé K, Eron J, Frater J, Gandhi RT, Geleziunas R, Goulder P, Hanna GJ, Jefferys R, Johnston R, Kuritzkes D, Li JZ, Likhitwonnawut U, van Lunzen J, Martinez-Picado J, Miller V, Montaner LJ, Nixon DF, Palm D, Pantaleo G, Peay H, Persaud D, Salzwedel J, Salzwedel K, Schacker T, Sheikh V, Søgaard OS, Spudich S, Stephenson K, Sugarman J, Taylor J, Tebas P, Tiemessen CT, Tressler R, Weiss CD, Zheng L, Robb ML, Michael NL, Mellors JW, Deeks SG, Walker BD. Recommendations for analytical antiretroviral treatment interruptions in HIV research trials—report of a consensus meeting. The Lancet HIV 2019, 6: e259-e268. PMID: 30885693, PMCID: PMC6688772, DOI: 10.1016/s2352-3018(19)30052-9.Peer-Reviewed Original ResearchConceptsAnalytical antiretroviral treatment interruptionsAntiretroviral treatment interruptionAntiretroviral therapyHIV researchTreatment interruptionSustained viral controlSafety of interventionsNovel therapeutic interventionsViral setpointViral suppressionViral loadImmunological markersViral controlConsensus meetingTrial designConcept trialTherapeutic interventionsTrialsInterventionRiskATI studiesMeeting of stakeholdersAdvocacy groupsHIVGroup
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 cells
2016
Neurocognitive Impairment of HIV Elite Controllers: Feature of Viral Suppression and Inflammation? (S53.004)
Bhatia N, Lee E, Fuchs D, Gisslen M, Zetterberg H, Russell A, Shacklett B, Price R, Spudich S. Neurocognitive Impairment of HIV Elite Controllers: Feature of Viral Suppression and Inflammation? (S53.004). Neurology 2016, 86 DOI: 10.1212/wnl.86.16_supplement.s53.004.Peer-Reviewed Original Research
2015
Plasma Concentration of the Neurofilament Light Protein (NFL) is a Biomarker of CNS Injury in HIV Infection: A Cross-Sectional Study
Gisslén M, Price RW, Andreasson U, Norgren N, Nilsson S, Hagberg L, Fuchs D, Spudich S, Blennow K, Zetterberg H. Plasma Concentration of the Neurofilament Light Protein (NFL) is a Biomarker of CNS Injury in HIV Infection: A Cross-Sectional Study. EBioMedicine 2015, 3: 135-140. PMID: 26870824, PMCID: PMC4739412, DOI: 10.1016/j.ebiom.2015.11.036.Peer-Reviewed Original ResearchConceptsNeurofilament light proteinHIV-associated dementiaCSF NFL concentrationsCNS injuryHIV infectionNfL concentrationsPlasma concentrationsCSF neurofilament light proteinNeurofilament light chain proteinSingle molecule array immunoassayHIV-negative controlsUntreated HIV infectionReliable blood biomarkersCross-sectional studySimilar age-related increasesAge-related increaseResearch settingsNFL changesHIV-negativeViral suppressionNeuronal injuryAntiretroviral treatmentHIV-positiveCross-sectional designSystemic disease
2014
Cerebrospinal Fluid (CSF) Neuronal Biomarkers across the Spectrum of HIV Infection: Hierarchy of Injury and Detection
Peterson J, Gisslen M, Zetterberg H, Fuchs D, Shacklett BL, Hagberg L, Yiannoutsos CT, Spudich SS, Price RW. Cerebrospinal Fluid (CSF) Neuronal Biomarkers across the Spectrum of HIV Infection: Hierarchy of Injury and Detection. PLOS ONE 2014, 9: e116081. PMID: 25541953, PMCID: PMC4277428, DOI: 10.1371/journal.pone.0116081.Peer-Reviewed Original ResearchConceptsNeurofilament light chain proteinT-tau levelsNeuronal biomarkersViral suppressionHIV infectionPrimary infectionCentral nervous system HIV infectionCSF t-tau levelsCSF Aβ peptidesHIV disease progressionAge-adjusted normsSoluble amyloid precursorHierarchy of sensitivityBlood CD4CD4 50HAD patientsHAD subjectsCD4 declineNeuronal injuryCross-sectional designProgressive injuryHIV progressionCSF biomarkersCSF concentrationsDisease progressionTreatment 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 impairmentTherapyDiseasePatientsDysfunctionPathophysiology
2013
Cerebrospinal fluid neopterin decay characteristics after initiation of antiretroviral therapy
Yilmaz A, Yiannoutsos CT, Fuchs D, Price RW, Crozier K, Hagberg L, Spudich S, Gisslén M. Cerebrospinal fluid neopterin decay characteristics after initiation of antiretroviral therapy. Journal Of Neuroinflammation 2013, 10: 828. PMID: 23664008, PMCID: PMC3657550, DOI: 10.1186/1742-2094-10-62.Peer-Reviewed Original ResearchConceptsCSF neopterin levelsAntiretroviral therapyNeopterin levelsCerebrospinal fluidCSF neopterinHAD patientsMacrophage activationART-mediated viral suppressionCommencement of ARTHigher pre-ART levelsCSF neopterin concentrationsPre-ART levelsProlonged antiretroviral therapySuppressive antiretroviral therapySet-point levelsBlood neopterinHAD subjectsART initiationAsymptomatic HIVTreatment-naïveViral suppressionNeopterin concentrationsImmune activationMost HIVHIV
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 suppression
2010
Cerebrospinal fluid in HIV-1 systemic viral controllers: absence of HIV-1 RNA and intrathecal inflammation
Probasco JC, Deeks SG, Lee E, Hoh R, Hunt PW, Liegler T, Price RW, Spudich SS. Cerebrospinal fluid in HIV-1 systemic viral controllers: absence of HIV-1 RNA and intrathecal inflammation. AIDS 2010, 24: 1001-1005. PMID: 20299968, DOI: 10.1097/qad.0b013e328331e15b.Peer-Reviewed Original ResearchConceptsHIV RNA levelsViral controllersIntrathecal inflammationCSF white blood cell countUndetectable plasma HIV RNA levelsCerebrospinal fluid HIV RNACSF HIV RNA levelsPlasma HIV RNA levelsTreatment-mediated viral suppressionWhite blood cell countCSF HIV infectionIP-10 concentrationsRNA levelsChronic systemic inflammationSubset of HIVHIV-1 RNAPlasma albumin ratioAbsence of therapyBlood cell countCentral nervous systemCross-sectional analysisCSF neopterinViremic HIVHIV RNAViral suppression