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 initiationPrevalence of detectable HIV-DNA and HIV-RNA in cerebrospinal fluid of youth with perinatal HIV and impaired cognition on antiretroviral therapy
Wagner T, Tierney C, Huang S, Nichols S, Malee K, Montañez N, Coletti A, Spiegel H, Krotje C, Bone F, Wilkins M, Abuogi L, Purswani M, Bearden A, Wiznia A, Agwu A, Chadwick E, Richman D, Gandhi M, Mehta P, Macatangay B, Spector S, Spudich S, Persaud D, Chahroudi A, Team F. Prevalence of detectable HIV-DNA and HIV-RNA in cerebrospinal fluid of youth with perinatal HIV and impaired cognition on antiretroviral therapy. AIDS 2024, 38: 1494-1504. PMID: 38814693, PMCID: PMC11239098, DOI: 10.1097/qad.0000000000003937.Peer-Reviewed Original ResearchCell-free HIV RNAAntiretroviral therapyHIV DNACentral nervous systemDetect HIV DNACerebrospinal fluidHIV RNAPerinatal HIVLong-term virologic suppressionFluid cognition composite scoresSuppressive antiretroviral therapyCerebrospinal fluid cellsHair antiretroviral concentrationsHIV DNA detectionQuantify HIVVirologic suppressionAntiretroviral concentrationsCD4 countCerebrospinal fluid collectionHIV infectionHIV GagPol DNANeurocognitive impairmentCognitive impairmentHIVHIV-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
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
2021
Cerebrospinal Fluid Viral Load Across the Spectrum of Untreated Human Immunodeficiency Virus Type 1 (HIV-1) Infection: A Cross-Sectional Multicenter Study
Ulfhammer G, Edén A, Antinori A, Brew BJ, Calcagno A, Cinque P, De Zan V, Hagberg L, Lin A, Nilsson S, Oprea C, Pinnetti C, Spudich S, Trunfio M, Winston A, Price RW, Gisslén M. Cerebrospinal Fluid Viral Load Across the Spectrum of Untreated Human Immunodeficiency Virus Type 1 (HIV-1) Infection: A Cross-Sectional Multicenter Study. Clinical Infectious Diseases 2021, 75: 493-502. PMID: 34747481, PMCID: PMC9427147, DOI: 10.1093/cid/ciab943.Peer-Reviewed Original ResearchConceptsCSF HIV RNAWhite blood cell countPlasma HIV RNAUntreated human immunodeficiency virus type 1 (HIV-1) infectionHuman immunodeficiency virus type 1 (HIV-1) infectionCSF white blood cell countVirus type 1 infectionHIV RNACopies/mLType 1 infectionMulticenter studyOpportunistic central nervous system infectionsCerebrospinal fluid HIV RNACerebrospinal fluid viral loadHigher CSF HIV RNALog10 copies/mLCentral nervous system infectionCross-sectional multicenter studyHIV RNA quantificationNervous system infectionTreatment-naive adultsBlood cell countLarge multicenter studyCNS compartmentalizationCSF discordance
2020
A randomized trial of vorinostat with treatment interruption after initiating antiretroviral therapy during acute HIV-1 infection
Kroon EDMB, Ananworanich J, Pagliuzza A, Rhodes A, Phanuphak N, Trautmann L, Mitchell JL, Chintanaphol M, Intasan J, Pinyakorn S, Benjapornpong K, Chang JJ, Colby DJ, Chomchey N, Fletcher JLK, Eubanks K, Yang H, Kapson J, Dantanarayana A, Tennakoon S, Gorelick RJ, Maldarelli F, Robb ML, Kim JH, Spudich S, Chomont N, Phanuphak P, Lewin SR, de Souza MS, Teams F. A randomized trial of vorinostat with treatment interruption after initiating antiretroviral therapy during acute HIV-1 infection. Journal Of Virus Eradication 2020, 6: 100004. PMID: 33251022, PMCID: PMC7646672, DOI: 10.1016/j.jve.2020.100004.Peer-Reviewed Original ResearchAcute HIV infectionAntiretroviral therapyTreatment interruptionViral loadAcute HIV-1 infectionHIV RNA copies/Open-label pilot studyPeripheral blood mononuclear cellsControl HIV replicationSubsequent treatment interruptionTotal HIV DNASerious adverse eventsHIV viral loadPlasma viral loadRNA copies/HIV-1 infectionBlood mononuclear cellsCopies/mLProportion of participantsCell-associated RNAAlternative treatment strategiesHistone deacetylase inhibitorsVL reboundHIV RNAViral reboundResting-state neural signatures of depressive symptoms in acute HIV
Philippi CL, Reyna L, Nedderman L, Chan P, Samboju V, Chang K, Phanuphak N, Ratnaratorn N, Hellmuth J, Benjapornpong K, Dumrongpisutikul N, Pothisri M, Robb ML, Ananworanich J, Spudich S, Valcour V, Paul R. Resting-state neural signatures of depressive symptoms in acute HIV. Journal Of NeuroVirology 2020, 26: 226-240. PMID: 31989446, PMCID: PMC7261250, DOI: 10.1007/s13365-020-00826-3.Peer-Reviewed Original ResearchConceptsResting-state functional connectivityAcute HIV infectionAnterior cingulate cortexDecreased resting-state functional connectivityDepressive symptomsAltered resting-state functional connectivityCombination antiretroviral therapyPersistent depressive symptomsUninfected control groupAmygdala seed regionPosterior cingulate/precuneusSymptoms of depressionVoxelwise regression analysesEmotion-related brain regionsAcute HIVChronic HIVThai HIVAntiretroviral therapyHIV RNASeed regionHIV infectionBlood biomarkersAHI groupLateral parietal regionsUninfected controls
2019
Defining cerebrospinal fluid HIV RNA escape: editorial review AIDS.
Winston A, Antinori A, Cinque P, Fox HS, Gisslen M, Henrich TJ, Letendre S, Persaud D, Price RW, Spudich S. Defining cerebrospinal fluid HIV RNA escape: editorial review AIDS. AIDS 2019, 33 Suppl 2: s107-s111. PMID: 31790376, DOI: 10.1097/qad.0000000000002252.Peer-Reviewed Original ResearchMarkers of CNS Injury in Adults Living With HIV With CSF HIV Not Detected vs Detected <20 Copies/mL
Farhadian SF, Mistry H, Kirchwey T, Chiarella J, Calvi R, Chintanaphol M, Patel P, Landry ML, Robertson K, Spudich SS. Markers of CNS Injury in Adults Living With HIV With CSF HIV Not Detected vs Detected <20 Copies/mL. Open Forum Infectious Diseases 2019, 6: ofz528. PMID: 31893212, PMCID: PMC6934883, DOI: 10.1093/ofid/ofz528.Peer-Reviewed Original ResearchAntiretroviral therapyHIV RNACerebrospinal fluidBlood-brain barrier integrityCentral nervous system pathologyCNS immune activationCSF HIV RNANervous system pathologyCSF HIVCSF RNAImmune activationCNS injuryCopies/Neuropsychological testingSystem pathologyBarrier integrityCNS parametersHIVStandard assayExecutive functionRNAInjuryTherapySignificance of RNAPathologyPersistent HIV-infected cells in cerebrospinal fluid are associated with poorer neurocognitive performance
Spudich S, Robertson KR, Bosch RJ, Gandhi RT, Cyktor JC, Mar H, Macatangay BJ, Lalama CM, Rinaldo C, Collier AC, Godfrey C, Eron JJ, McMahon D, Jacobs JL, Koontz D, Hogg E, Vecchio A, Mellors JW. Persistent HIV-infected cells in cerebrospinal fluid are associated with poorer neurocognitive performance. Journal Of Clinical Investigation 2019, 129: 3339-3346. PMID: 31305262, PMCID: PMC6668666, DOI: 10.1172/jci127413.Peer-Reviewed Original ResearchConceptsLong-term antiretroviral therapyPeripheral blood mononuclear cellsAntiretroviral therapyHIV RNACerebrospinal fluidPoorer neurocognitive performanceInflammatory biomarkersNeurocognitive performanceCell-associated HIV DNACell-free HIV RNAHigher plasma HIV RNAYears of ARTCSF HIV RNACSF inflammatory biomarkersWorse neurocognitive outcomesNadir CD4 countPlasma HIV RNABlood mononuclear cellsQuantitative PCRGlobal deficit scoreHalf of individualsCell-free RNACSF supernatantHIV persistenceCD4 count
2018
Structural and functional brain imaging in acute HIV
Samboju V, Philippi CL, Chan P, Cobigo Y, Fletcher JLK, Robb M, Hellmuth J, Benjapornpong K, Dumrongpisutikul N, Pothisri M, Paul R, Ananworanich J, Spudich S, Valcour V, 010/RV254 S, teams R. Structural and functional brain imaging in acute HIV. NeuroImage Clinical 2018, 20: 327-335. PMID: 30101063, PMCID: PMC6082997, DOI: 10.1016/j.nicl.2018.07.024.Peer-Reviewed Original ResearchConceptsResting-state functional connectivityAcute HIV infectionAntiretroviral treatmentDiffusion tensor imagingAHI groupNPZ-4HIV RNARadial diffusivityFractional anisotropyCerebrospinal fluidHigher CD4 cell countsParahippocampal cortexHigher resting-state functional connectivityCombination antiretroviral treatmentHIV disease variablesLeft parahippocampal cortexMean CD4 countPlasma HIV RNACD4 cell countCopies/mLNeuropsychological testing performanceMicrostructural white matterFunctional brain integrityMiddle frontal gyrusSuperior longitudinal fasciculusDistribution 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 ResearchConceptsCD4/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
Acute Retroviral Syndrome Is Associated With High Viral Burden, CD4 Depletion, and Immune Activation in Systemic and Tissue Compartments
Crowell TA, Colby DJ, Pinyakorn S, Fletcher JLK, Kroon E, Schuetz A, Krebs SJ, Slike BM, Leyre L, Chomont N, Jagodzinski LL, Sereti I, Utay NS, Dewar R, Rerknimitr R, Chomchey N, Trichavaroj R, Valcour VG, Spudich S, Michael NL, Robb ML, Phanuphak N, Ananworanich J, Teeratakulpisarn N, Sacdalan C, Sutthichom D, Rattanamanee S, Prueksakaew P, Ubolyam S, Eamyoung P, Puttamaswin S, Tipsuk S, Karnsomlap P, Ridtitid W, Connell R, Akapirat S, Phuang-Ngern Y, Sukhumvittaya S, Sajjaweerawan C, Jongrakthaitae S, Saetun P, Tragonlugsana N, Nuntapinit B, Tantibul N, Savadsuk H, Tovanabutr S. Acute Retroviral Syndrome Is Associated With High Viral Burden, CD4 Depletion, and Immune Activation in Systemic and Tissue Compartments. Clinical Infectious Diseases 2017, 66: 1540-1549. PMID: 29228130, PMCID: PMC5930255, DOI: 10.1093/cid/cix1063.Peer-Reviewed Original ResearchConceptsHigh viral burdenAcute retroviral syndromeAntiretroviral therapyCD4 depletionViral burdenImmune activationAdverse long-term clinical outcomesVoluntary human immunodeficiency virus (HIV) testingPlasma tumor necrosis factor alphaWeeks of ARTHuman immunodeficiency virus (HIV) testingLong-term clinical outcomesTumor necrosis factor alphaHigher HIV RNATotal HIV DNASuppressive antiretroviral therapyC-reactive proteinSigns/symptomsNecrosis factor alphaUnderwent lumbar punctureMultiple body compartmentsARS diagnosisFiebig stagesSigmoid biopsiesHIV RNADepression and Anxiety are Common in Acute HIV Infection and Associate with Plasma Immune Activation
Hellmuth J, Colby D, Valcour V, Suttichom D, Spudich S, Ananworanich J, Prueksakaew P, Sailasuta N, Allen I, Jagodzinski LL, Slike B, Ochi D, Paul R, on behalf of the RV254/SEARCH 010 Study Group. Depression and Anxiety are Common in Acute HIV Infection and Associate with Plasma Immune Activation. AIDS And Behavior 2017, 21: 3238-3246. PMID: 28484888, PMCID: PMC5830305, DOI: 10.1007/s10461-017-1788-4.Peer-Reviewed Original ResearchConceptsAcute HIV infectionCombination antiretroviral therapyPlasma HIV RNAHIV infectionImmune activationCD4 countHIV RNAPlasma neopterinStudy entryBaseline plasma HIV RNALow CD4 countRelevant depressive symptomsAnxiety symptomsCerebrospinal fluid measuresAssessment of depressionAHI participantsAntiretroviral therapyBlood markersObservational studyDepressive symptomsMacrophage activationAffective symptomsPossible associationSymptomsFluid measuresHigh Number of Activated CD8+ T Cells Targeting HIV Antigens Are Present in Cerebrospinal Fluid in Acute HIV Infection
Kessing CF, Spudich S, Valcour V, Cartwright P, Chalermchai T, Fletcher JL, Takata H, Nichols C, Josey B, Slike B, Krebs S, Sailsuta N, Lerdlum S, Jagodzinski L, Tipsuk S, Suttichom D, Rattanamanee S, Zetterberg H, Hellmuth J, Phanuphak N, Robb M, Michael N, Ananworanich J, Trautmann L. High Number of Activated CD8+ T Cells Targeting HIV Antigens Are Present in Cerebrospinal Fluid in Acute HIV Infection. JAIDS Journal Of Acquired Immune Deficiency Syndromes 2017, 75: 108-117. PMID: 28177966, PMCID: PMC5388590, DOI: 10.1097/qai.0000000000001301.Peer-Reviewed Original ResearchConceptsAcute HIV infectionCD8 T cellsChronic HIV infectionHIV infectionT cellsCerebrospinal fluidCD8 T cell effector functionsHIV-specific CD8 T cellsCentral nervous system infiltrationT cell effector functionT cell receptor repertoireCSF HIV RNACombination antiretroviral therapyTCR Vbeta repertoireCell effector functionsCell receptor repertoireHIV specificitiesAntiretroviral therapyCNS inflammationHIV RNAVbeta repertoireMicroglial activationActivated CD8HIV antigenHIV epitopes
2016
Neurologic signs and symptoms frequently manifest in acute HIV infection
Hellmuth J, Fletcher JL, Valcour V, Kroon E, Ananworanich J, Intasan J, Lerdlum S, Narvid J, Pothisri M, Allen I, Krebs SJ, Slike B, Prueksakaew P, Jagodzinski LL, Puttamaswin S, Phanuphak N, Spudich S, Phanuphak P, Phanuphak N, Colby D, Chalermchai T, Chomchey N, Suttichom D, Rattanamanee S, Sangtawan P, Rattanamanee S, Nuntapinit B, Rakyat P, Inprakong S, Lucksanawong S, Ruangjan P, Nuchwong A, Kruacharoen P, O’Connell R, Adams C, Clifford K, Wendelken L, Le L, Mistry H, Tovanabutra S, Pinyakorn S, Robb M, Paul R. Neurologic signs and symptoms frequently manifest in acute HIV infection. Neurology 2016, 87: 148-154. PMID: 27287217, PMCID: PMC4940060, DOI: 10.1212/wnl.0000000000002837.Peer-Reviewed Original ResearchConceptsCombination antiretroviral therapyAcute HIV infectionNeurologic findingsHIV infectionAcute HIVNeurologic manifestationsNeurologic evaluationHIV infection durationLog10 HIV RNASevere neurologic manifestationsStructural neuroimaging abnormalitiesCART initiationAntiretroviral therapyHIV RNAInflammatory markersMotor findingsNeuroimaging abnormalitiesStudy entryNeurologic signsBrain MRIInfection durationCognitive symptomsViral factorsInfectionDiagnosisCognitive 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
Neuropsychological Impairment in Acute HIV and the Effect of Immediate Antiretroviral Therapy
Kore I, Ananworanich J, Valcour V, Fletcher JL, Chalermchai T, Paul R, Reynolds J, Tipsuk S, Ubolyam S, Rattanamanee S, Jagodzinski L, Kim J, Spudich S. Neuropsychological Impairment in Acute HIV and the Effect of Immediate Antiretroviral Therapy. JAIDS Journal Of Acquired Immune Deficiency Syndromes 2015, 70: 393-399. PMID: 26509933, PMCID: PMC4625393, DOI: 10.1097/qai.0000000000000746.Peer-Reviewed Original ResearchNeurological 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 antagonists
2014
Longitudinal 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