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 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 initiationFramingham 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 outcome
2022
Individual 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 infection
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 provirusesInflammationTherapyProvirus
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 pathwaysDysfunctionTherapySwitch 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 symptoms
2018
Single-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 subsetsInfectionAnti-Human Immunodeficiency Virus Antibodies in the Cerebrospinal Fluid: Evidence of Early Treatment Impact on Central Nervous System Reservoir?
Burbelo PD, Price RW, Hagberg L, Hatano H, Spudich S, Deeks SG, Gisslén M. Anti-Human Immunodeficiency Virus Antibodies in the Cerebrospinal Fluid: Evidence of Early Treatment Impact on Central Nervous System Reservoir? The Journal Of Infectious Diseases 2018, 217: 1024-1032. PMID: 29401308, PMCID: PMC5939835, DOI: 10.1093/infdis/jix662.Peer-Reviewed Original ResearchConceptsCentral nervous systemHuman immunodeficiency virusAntiretroviral therapyLong-term treatmentCerebrospinal fluidHIV antibodiesCSF antibodiesEarly infectionBlood antibodyChronic infectionVirus antibodiesCentral nervous system reservoirAnti-human immunodeficiency virus antibodiesHuman immunodeficiency virus (HIV) antibodyEarly ART initiationMarkers of persistenceEffective antiretroviral therapySuppressive antiretroviral therapyPre-exposure prophylaxisART initiationHIV persistenceCNS infectionHIV reservoirImmunodeficiency virusBerlin patient
2016
Immune Activation and HIV-Specific CD8+ T Cells in Cerebrospinal Fluid of HIV Controllers and Noncontrollers
Ganesh A, Lemongello D, Lee E, Peterson J, McLaughlin BE, Ferre AL, Gillespie GM, Fuchs D, Deeks SG, Hunt PW, Price RW, Spudich SS, Shacklett BL. Immune Activation and HIV-Specific CD8+ T Cells in Cerebrospinal Fluid of HIV Controllers and Noncontrollers. AIDS Research And Human Retroviruses 2016, 32: 791-800. PMID: 27019338, PMCID: PMC4971411, DOI: 10.1089/aid.2015.0313.Peer-Reviewed Original ResearchMeSH KeywordsADP-ribosyl Cyclase 1Anti-HIV AgentsAntiretroviral Therapy, Highly ActiveCD4 Lymphocyte CountCD8-Positive T-LymphocytesDisease ResistanceGene ExpressionHIV InfectionsHIV-1HLA-DR AntigensHost-Pathogen InteractionsHumansLeukocyte Common AntigensLymphocyte ActivationReceptors, CCR5Receptors, CCR7RNA, ViralViral LoadViremiaConceptsCentral nervous systemHIV controllersAntiretroviral therapyT cellsCerebrospinal fluidViral loadCopies/HIV-specific T cellsMajor histocompatibility complex class IActivation markers CD38CSF viral loadHIV-specific CD8Undetectable plasma viremiaExpression of CCR5Majority of HIVPlasma viral loadEffector memory cellsHIV-negative controlsHistocompatibility complex class IAbsence of therapyComplex class ILong-term controlPlasma viremiaElite controllersHIV infection
2015
Neurological Response to cART vs. cART plus Integrase Inhibitor and CCR5 Antagonist Initiated during Acute HIV
Valcour VG, Spudich SS, Sailasuta N, Phanuphak N, Lerdlum S, Fletcher JL, Kroon ED, Jagodzinski LL, Allen IE, Adams CL, Prueksakaew P, Slike BM, Hellmuth JM, Kim JH, Ananworanich J, . Neurological Response to cART vs. cART plus Integrase Inhibitor and CCR5 Antagonist Initiated during Acute HIV. PLOS ONE 2015, 10: e0142600. PMID: 26555069, PMCID: PMC4640512, DOI: 10.1371/journal.pone.0142600.Peer-Reviewed Original ResearchConceptsCombination antiretroviral therapyStandard combination antiretroviral therapyLog10 HIV RNAAcute HIVCSF cytokinesHIV RNACentral nervous system outcomesIntegrase inhibitorsGamma-induced protein 10Duration of HIVFiebig stages IAcute HIV infectionHIV RNA levelsCNS outcomesAntiretroviral therapyInflammatory markersWeek 24Antiretroviral treatmentHIV infectionPlasma neopterinRandomized armProspective evaluationMean ageHealthy controlsCCR5 antagonistsCerebral 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
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 ResearchMeSH KeywordsAIDS Dementia ComplexAnti-HIV AgentsDrug-Related Side Effects and Adverse ReactionsHIV InfectionsHumansConceptsCentral 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 mediatorsLongitudinal Characterization of Depression and Mood States Beginning in Primary HIV Infection
Gold JA, Grill M, Peterson J, Pilcher C, Lee E, Hecht FM, Fuchs D, Yiannoutsos CT, Price RW, Robertson K, Spudich S. Longitudinal Characterization of Depression and Mood States Beginning in Primary HIV Infection. AIDS And Behavior 2014, 18: 1124-1132. PMID: 24385231, DOI: 10.1007/s10461-013-0688-5.Peer-Reviewed Original ResearchConceptsBeck Depression InventoryPrimary HIV infectionAntiretroviral therapyCerebrospinal fluidHIV infectionInitiation of ARTPresence of ARTNeuropsychological performanceMood States (POMS) subscalesPlasma HIV RNAEvaluation of moodChronic HIVHIV durationPHI subjectsHIV RNATotal followProspective studyAlbumin ratioBDI criteriaBDI scoresEarly courseClinical depressionNeurological diseasesLongitudinal courseDepression history
2013
An Example of Genetically Distinct HIV Type 1 Variants in Cerebrospinal Fluid and Plasma During Suppressive Therapy
Dahl V, Gisslen M, Hagberg L, Peterson J, Shao W, Spudich S, Price RW, Palmer S. An Example of Genetically Distinct HIV Type 1 Variants in Cerebrospinal Fluid and Plasma During Suppressive Therapy. The Journal Of Infectious Diseases 2013, 209: 1618-1622. PMID: 24338353, PMCID: PMC3997583, DOI: 10.1093/infdis/jit805.Peer-Reviewed Original ResearchMeSH KeywordsAnti-HIV AgentsGenetic VariationGenome, ViralHIV InfectionsHIV-1HumansMaleRNA, ViralViral LoadConceptsCentral nervous systemSuppressive therapyTreatment initiationNervous systemPlasma sequencesHIV Type 1 VariantsHuman immunodeficiency virus type 1Immunodeficiency virus type 1Cerebrospinal fluid specimensType 1 variantsVirus type 1CSF sequencesViral persistenceHIV-1Cerebrospinal fluidFluid specimensTherapyType 1Virus replicationMajor causePlasma samplesCSFViral evolutionSubjectsLittle evidenceHIV and Neurocognitive Dysfunction
Spudich S. HIV and Neurocognitive Dysfunction. Current HIV/AIDS Reports 2013, 10: 235-243. PMID: 23860944, PMCID: PMC3732773, DOI: 10.1007/s11904-013-0171-y.Peer-Reviewed Original ResearchConceptsIrreversible CNS injuryEffective antiretroviral therapySpectrum of HIVQuality of lifeEffect of treatmentCommunity of patientsAntiretroviral therapyCNS infectionNeurologic injuryHIV infectionProgressive injuryImmune activationCNS injuryCognitive dysfunctionNeurocognitive disordersNeurocognitive dysfunctionHIVCognitive impairmentViral replicationInjuryBeneficial reductionDysfunctionInfectionDisordersPatients
2012
Change in Brain Magnetic Resonance Spectroscopy after Treatment during Acute HIV Infection
Sailasuta N, Ross W, Ananworanich J, Chalermchai T, DeGruttola V, Lerdlum S, Pothisri M, Busovaca E, Ratto-Kim S, Jagodzinski L, Spudich S, Michael N, Kim JH, Valcour V, Phanuphak N, Teeratakulpisarn N, Fletcher J, Suttichom D, Pinyakorn S, Rattanamanee S, Chomchey N, Mangum P, Ubolyam S, Suwanwela N, Chaisinanunkul N, Suthiponpaisan U, Sutthapas C, deSouza M, Ngauy V, Trichavaroj R, Akapirat S, Marovich M, Wendelken L, Busovaca E, Liu C, Mun E, Miller B. Change in Brain Magnetic Resonance Spectroscopy after Treatment during Acute HIV Infection. PLOS ONE 2012, 7: e49272. PMID: 23229129, PMCID: PMC3500278, DOI: 10.1371/journal.pone.0049272.Peer-Reviewed Original ResearchConceptsOccipital gray matterAntiretroviral therapyHIV infectionFrontal gray matterFrontal white matterN-acetyl aspartateBasal gangliaControl subjectsGray matterHIV-negative control subjectsInitiation of ARTSingle-voxel proton magnetic resonance spectroscopyBrain magnetic resonance spectroscopyAcute HIV infectionEarly antiretroviral therapyBrain metabolite levelsNegative control subjectsProton magnetic resonance spectroscopyMagnetic resonance spectroscopyHIV subjectsBrain inflammationNeuronal injuryHIV casesCNS injuryCellular inflammation