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
2022
HIV 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 compartmentCerebrospinal 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 discordanceCompartmentalization 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
Minimal detection of cerebrospinal fluid escape after initiation of antiretroviral therapy in acute HIV-1 infection.
Handoko R, Chan P, Jagodzinski L, Pinyakorn S, Ubolyam S, Phanuphak N, Sacdalan C, Kroon E, Dumrongpisutikul N, Paul R, Valcour V, Ananworanich J, Vasan S, Spudich S. Minimal detection of cerebrospinal fluid escape after initiation of antiretroviral therapy in acute HIV-1 infection. AIDS 2020, 35: 777-782. PMID: 33306551, PMCID: PMC7969409, DOI: 10.1097/qad.0000000000002786.Peer-Reviewed Original ResearchConceptsAcute HIV-1 infectionHIV-1 RNACentral nervous systemCSF escapeAntiretroviral therapyHIV-1 infectionWeek 96Week 24HIV-1CSF HIV-1 RNAInitiation of ARTLong-term neurological outcomePlasma HIV-1 RNAWeeks of ARTProspective cohort studyPersistence of HIVHIV-1 persistenceLevels of CSFYears of treatmentHIV-1 replicationNeurological outcomeCohort studyVoluntary counselingChronic infectionEarly treatmentSelective 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
Potential 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 diseasesDefining 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 ResearchNeurosyphilis During Acute HIV Infection: A CNS Immunologic and Virologic Characterization.
Chan P, Dumrongpisutikul N, Subra C, Colby DJ, Kroon E, Fletcher J, Sacdalan C, Phanuphak N, Valcour V, Ananworanich J, Trautmann L, Spudich S. Neurosyphilis During Acute HIV Infection: A CNS Immunologic and Virologic Characterization. JAIDS Journal Of Acquired Immune Deficiency Syndromes 2019, 82: e34-e37. PMID: 31180994, PMCID: PMC10126948, DOI: 10.1097/qai.0000000000002114.Peer-Reviewed Original ResearchDeep Sequencing Reveals Central Nervous System Compartmentalization in Multiple Transmitted/Founder Virus Acute HIV-1 Infection
Tovanabutra S, Sirijatuphat R, Pham PT, Bonar L, Harbolick EA, Bose M, Song H, Chang D, Oropeza C, O’Sullivan A, Balinang J, Kroon E, Colby DJ, Sacdalan C, Hellmuth J, Chan P, Prueksakaew P, Pinyakorn S, Jagodzinski LL, Sutthichom D, Pattamaswin S, de Souza M, Gramzinski RA, Kim JH, Michael NL, Robb ML, Phanuphak N, Ananworanich J, Valcour V, Kijak GH, Sanders-Buell E, Spudich S, Core T, Team T. Deep Sequencing Reveals Central Nervous System Compartmentalization in Multiple Transmitted/Founder Virus Acute HIV-1 Infection. Cells 2019, 8: 902. PMID: 31443253, PMCID: PMC6721674, DOI: 10.3390/cells8080902.Peer-Reviewed Original ResearchConceptsAcute HIV-1 infectionCentral nervous systemHIV-1 infectionCerebrospinal fluidCNS compartmentalizationHIV-1HIV-1 compartmentalizationHIV-1 exposureHIV-1 neuropathogenesisHIV-1 reservoirSingle-genome sequencingHIV reservoirFounder virusesRemission strategiesNeurological impairmentNervous systemF infectionsViral replicationInfectionPotential long-term implicationsNext-generation sequencingEnvelope geneTissue compartmentsF variantLong-term implicationsPersistent 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 countVery Early Initiation of Antiretroviral Therapy During Acute HIV Infection Is Associated With Normalized Levels of Immune Activation Markers in Cerebrospinal Fluid but Not in Plasma
Hellmuth J, Slike BM, Sacdalan C, Best J, Kroon E, Phanuphak N, Fletcher JLK, Prueksakaew P, Jagodzinski LL, Valcour V, Robb M, Ananworanich J, Allen IE, Krebs SJ, Spudich S. Very Early Initiation of Antiretroviral Therapy During Acute HIV Infection Is Associated With Normalized Levels of Immune Activation Markers in Cerebrospinal Fluid but Not in Plasma. The Journal Of Infectious Diseases 2019, 220: 1885-1891. PMID: 30668739, PMCID: PMC6833977, DOI: 10.1093/infdis/jiz030.Peer-Reviewed Original ResearchConceptsAcute HIV infectionAntiretroviral therapyART initiationCerebrospinal fluidWeek 96Week 24HIV infectionImmune activationAHI groupHuman immunodeficiency virus (HIV) infectionEarly ART initiationPlasma CCL2 levelsTrajectory of HIVChronic immune activationImmune activation markersSuppressive antiretroviral therapyImmunodeficiency virus infectionInterleukin-6 levelsMarkers of inflammationPlasma neopterin levelsWeeks of treatmentCentral nervous systemART regimenCCL2 levelsNeopterin levels
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 cellsCentral Nervous System Inflammation and Infection during Early, Nonaccelerated Simian-Human Immunodeficiency Virus Infection in Rhesus Macaques
Hsu DC, Sunyakumthorn P, Wegner M, Schuetz A, Silsorn D, Estes JD, Deleage C, Tomusange K, Lakhashe SK, Ruprecht RM, Lombardini E, Im-Erbsin R, Kuncharin Y, Phuang-Ngern Y, Inthawong D, Chuenarom W, Burke R, Robb ML, Ndhlovu LC, Ananworanich J, Valcour V, O'Connell RJ, Spudich S, Michael NL, Vasan S. Central Nervous System Inflammation and Infection during Early, Nonaccelerated Simian-Human Immunodeficiency Virus Infection in Rhesus Macaques. Journal Of Virology 2018, 92: 10.1128/jvi.00222-18. PMID: 29563297, PMCID: PMC5952152, DOI: 10.1128/jvi.00222-18.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigens, CDAntigens, Differentiation, MyelomonocyticBrainCD4 Lymphocyte CountCD4-Positive T-LymphocytesCells, CulturedDisease Models, AnimalHIV-1HumansMacaca mulattaMacrophagesMeningesMicrogliaMonocytesParenchymal TissueReceptors, Cell SurfaceRNA, ViralSimian Acquired Immunodeficiency SyndromeSimian immunodeficiency virusViral LoadConceptsSimian-human immunodeficiency virusSimian immunodeficiency virusCD68/CD163Immunodeficiency virus infectionCentral nervous systemBrain parenchymaHIV envelopeImmunodeficiency virusVirus infectionEarly human immunodeficiency virus (HIV) infectionSimian-human immunodeficiency virus (SHIV) infectionCentral nervous system inflammationHuman immunodeficiency virus (HIV) infectionCentral nervous system involvementPathogenic simian immunodeficiency virusRhesus macaquesT-cell-mediated processEarly clinical courseSHIV-infected animalsNervous system inflammationT-cell countsCell-mediated inflammationNervous system involvementEnd-stage diseaseHIV cure strategiesDistribution 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 markersAnti-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
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 measures
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