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 ResearchMeSH KeywordsAdultCD4-Positive T-LymphocytesFemaleHIV InfectionsHIV-1HumansInflammationMaleMiddle AgedRNA, ViralVirus ReplicationConceptsHIV-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 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 StatementsConceptsEarly 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 cellsFramingham 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
CD4dimCD8bright T cells are inversely associated with neuro-inflammatory markers among people with HIV
Albalawi Y, Shull T, Virdi A, Subra C, Mitchell J, Slike B, Jian N, Krebs S, Sacdalan C, Ratnaratorn N, Hsu D, Phanuphak N, Spudich S, Trautmann L, Al-Harthi L. CD4dimCD8bright T cells are inversely associated with neuro-inflammatory markers among people with HIV. AIDS 2023, 38: 1-7. PMID: 37792358, PMCID: PMC10715695, DOI: 10.1097/qad.0000000000003743.Peer-Reviewed Original ResearchMeSH KeywordsCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesCognitionHIV InfectionsHumansNeuroinflammatory DiseasesConceptsCombination antiretroviral therapyT cellsWeeks 0CD4-CD8Cerebrospinal fluidImmune activationSoluble markersSuppressive combination antiretroviral therapyPeripheral blood T cellsNeuro-inflammatory markersSubset of CD8Anti-inflammatory propertiesBlood T cellsConfidence intervalsPlasma of peopleT-cell typeCART initiationCSF neopterinPlasma RANTESAntiretroviral therapyWeek 24IP-10IL-6Lumbar punctureIL-8Antiretroviral 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 outcomeBiotypes 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 influxVirusBrain 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 ResearchMeSH KeywordsAdolescentAdultBrainCross-Sectional StudiesHIVHIV InfectionsHumansMagnetic Resonance ImagingMaleMiddle AgedYoung AdultConceptsAcute 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
2022
Correlation between CD4/CD8 ratio and neurocognitive performance during early HIV infection
Le LT, Price RW, Gisslén M, Zetterberg H, Emu B, Fabre R, Christian P, Andersen S, Spudich S, Vassallo M. Correlation between CD4/CD8 ratio and neurocognitive performance during early HIV infection. HIV Medicine 2022, 24: 442-452. PMID: 36134890, DOI: 10.1111/hiv.13411.Peer-Reviewed Original ResearchMeSH KeywordsAnti-Retroviral AgentsCD4-CD8 RatioCD8-Positive T-LymphocytesHIV InfectionsHumansRetrospective StudiesConceptsCD4/CD8 ratioPrimary HIV infectionCD8 ratioImmune activationHIV infectionNeuronal injuryAntiretroviral treatmentNeurocognitive performanceMean CD4/CD8 ratioCSF neurofilament light chainART-naïve participantsEarly HIV infectionCerebrospinal fluid markersNeurofilament light chainNeuropsychological testing performancePsychomotor speed performancePHI participantsStudy cohortCSF markersChronic infectionBrain injuryRetrospective analysisFluid markersInfectionInjuryLong-term antiretroviral therapy initiated in acute HIV infection prevents residual dysfunction of HIV-specific CD8+ T cells
Takata H, Kakazu J, Mitchell J, Kroon E, Colby D, Sacdalan C, Bai H, Ehrenberg P, Geretz A, Buranapraditkun S, Pinyakorn S, Intasan J, Tipsuk S, Suttichom D, Prueksakaew P, Chalermchai T, Chomchey N, Phanuphak N, de Souza M, Michael N, Robb M, Haddad E, Crowell T, Vasan S, Valcour V, Douek D, Thomas R, Rolland M, Chomont N, Ananworanich J, Trautmann L, Teeratakulpisarn N, Pattanachaiwit S, Sriplienchan S, Tantivitayakul P, Kanaprach R, Ruxrungtham K, Dumrongpisutikul N, Rojnuckarin P, Chottanapund S, Poltavee K, Luekasemsuk T, Savadsuk H, Puttamsawin S, Benjapornpong K, Ratnaratorn N, Tangnaree K, Munkong C, Thaimanee R, Eamyoung P, Ubolyam S, Lerdlum S, Manasnayakorn S, Rerknimitr R, Sirivichayakul S, Wattanaboonyongcharoen P, Cowden J, Schuetz A, Akapirat S, Churikanont N, Getchalarat S, Hsu D, Turk E, Butterworth O, Milazzo M, Eller L, Ake J, Eller L, Spudich S, Fox L, Ratto-Kim S, DeGruttola V, Chinvarun Y, Sithinamsuwan P, Fletcher J, Shiramizu B, Schuetz A. Long-term antiretroviral therapy initiated in acute HIV infection prevents residual dysfunction of HIV-specific CD8+ T cells. EBioMedicine 2022, 84: 104253. PMID: 36088683, PMCID: PMC9471490, DOI: 10.1016/j.ebiom.2022.104253.Peer-Reviewed Original ResearchConceptsHIV-specific CD8Long-term antiretroviral therapyFunctional HIV-specific CD8Acute HIV infectionAntiretroviral therapyT cellsART initiationHIV infectionResidual dysfunctionVitro recallTCF-1 expressionChronic HIV infectionHIV remission strategiesT cell numbersT cell responsesInfection ex vivoStem cell-like propertiesCell numberCell-like propertiesART interruptionSpontaneous controllersViral reboundAcute infectionHIV remissionRemission strategiesNeuropathogenesis 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 activationIndividual Differences in CD4/CD8 T-Cell Ratio Trajectories and Associated Risk Profiles Modeled From Acute HIV Infection
Paul R, Cho K, Bolzenius J, Sacdalan C, Ndhlovu LC, Trautmann L, Krebs S, Tipsuk S, Crowell TA, Suttichom D, Colby DJ, Premeaux TA, Phanuphak N, Chan P, Kroon E, Vasan S, Hsu D, Carrico A, Valcour V, Ananworanich J, Robb ML, Ake JA, Sriplienchan S, Spudich S, Team F. Individual Differences in CD4/CD8 T-Cell Ratio Trajectories and Associated Risk Profiles Modeled From Acute HIV Infection. Psychosomatic Medicine 2022, 84: 976-983. PMID: 36162059, PMCID: PMC9553252, DOI: 10.1097/psy.0000000000001129.Peer-Reviewed Original ResearchConceptsAcute HIV infectionCD4/CD8 T-cell ratioCD8 T-cell ratioAntiretroviral therapyT-cell countsT-cell recoveryT cell ratioHigh viral loadViral loadHigh CD8Slower CD4HIV infectionLower white blood cell countWeeks of ARTRisk profileWhite blood cell countT-cell trajectoriesMedian viral loadStandard antiretroviral therapyBlood cell countLower eosinophil countsWorse mental healthAHI participantsART onsetFiebig IImmunological, 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 ResearchMeSH KeywordsAdultAnti-HIV AgentsBenzoxazinesCognitionFemaleHeterocyclic Compounds, 3-RingHIV InfectionsHumansMaleRetrospective StudiesConceptsAcute 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 infectionHIV 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 benefitsSingle-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 expressionCD4HIV Disease Dynamics and Markers of Inflammation and CNS Injury During Primary HIV Infection and Their Relationship to Cognitive Performance
Longino AA, Paul R, Wang Y, Lama JR, Brandes P, Ruiz E, Correa C, Keating S, Spudich SS, Pilcher C, Vecchio A, Pasalar S, Ignacio R, Valdez R, Dasgupta S, Robertson K, Duerr A. HIV Disease Dynamics and Markers of Inflammation and CNS Injury During Primary HIV Infection and Their Relationship to Cognitive Performance. JAIDS Journal Of Acquired Immune Deficiency Syndromes 2022, 89: 183-190. PMID: 34629415, PMCID: PMC8752485, DOI: 10.1097/qai.0000000000002832.Peer-Reviewed Original ResearchConceptsAcute HIV infectionAntiretroviral therapyHIV infectionWeek 192CNS injuryCSF biomarkersNP scoresHigher pre-ART VLCognitive performanceChronic cognitive symptomsSustained antiretroviral therapyPrimary HIV infectionMarkers of inflammationCerebrospinal fluid biomarkersPsychosocial risk factorsART initiationCNS inflammationNeuronal injuryAcute infectionImmune activationFluid biomarkersRisk factorsHIV disease dynamicsInjury peaksCognitive symptoms
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 compartment