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 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
Compartmentalization 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 responseIschemic Stroke, Inflammation, and Endotheliopathy in COVID-19 Patients
McAlpine LS, Zubair AS, Maran I, Chojecka P, Lleva P, Jasne AS, Navaratnam D, Matouk C, Schindler J, Sheth KN, Chun H, Lee AI, Spudich S, Sharma R, Sansing LH. Ischemic Stroke, Inflammation, and Endotheliopathy in COVID-19 Patients. Stroke 2021, 52: e233-e238. PMID: 33966492, PMCID: PMC8140646, DOI: 10.1161/strokeaha.120.031971.Peer-Reviewed Original Research
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 subsetsInfection
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 RNA
2015
Cerebral 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
Progressive increase in central nervous system immune activation in untreated primary HIV-1 infection
Suh J, Sinclair E, Peterson J, Lee E, Kyriakides TC, Li FY, Hagberg L, Fuchs D, Price RW, Gisslen M, Spudich S. Progressive increase in central nervous system immune activation in untreated primary HIV-1 infection. Journal Of Neuroinflammation 2014, 11: 199. PMID: 25465205, PMCID: PMC4263211, DOI: 10.1186/s12974-014-0199-y.Peer-Reviewed Original ResearchConceptsPrimary HIV-1 infectionHIV-1 infectionCSF neopterinCerebrospinal fluidT cellsHIV infectionCentral nervous system immune activationUntreated primary HIV-1 infectionBaseline levelsEarly HIV-1 infectionCSF neopterin concentrationsNervous system inflammationMixed effects modelsCluster of differentiationMajority of subjectsCNS inflammationSystem inflammationAverage followNeopterin concentrationsHIV transmissionImmune activationLumbar punctureResultsA totalIntrathecal inflammationNatural courseTreatment 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
2012
Central Nervous System Viral Invasion and Inflammation During Acute HIV Infection
Valcour V, Chalermchai T, Sailasuta N, Marovich M, Lerdlum S, Suttichom D, Suwanwela NC, Jagodzinski L, Michael N, Spudich S, van Griensven F, de Souza M, Kim J, Ananworanich J. Central Nervous System Viral Invasion and Inflammation During Acute HIV Infection. The Journal Of Infectious Diseases 2012, 206: 275-282. PMID: 22551810, PMCID: PMC3490695, DOI: 10.1093/infdis/jis326.Peer-Reviewed Original ResearchConceptsHIV RNA levelsAcute HIV infectionCSF HIV RNA levelsCopies/mLHIV infectionCerebrospinal fluidHIV RNARNA levelsPlasma HIV RNA levelsCentral nervous system eventsHuman immunodeficiency virus (HIV) infectionCSF HIV RNAFiebig stages IIntrathecal immune activationAcute retroviral syndromeImmunodeficiency virus infectionNervous system eventsMagnetic resonance imagingMagnetic resonance spectroscopy characterizationCSF neopterinBrain inflammationCNS inflammationCSF levelsHIV transmissionImmune activation
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
2006
Treatment Benefit on Cerebrospinal Fluid HIV‐1 Levels in the Setting of Systemic Virological Suppression and Failure
Spudich S, Lollo N, Liegler T, Deeks SG, Price RW. Treatment Benefit on Cerebrospinal Fluid HIV‐1 Levels in the Setting of Systemic Virological Suppression and Failure. The Journal Of Infectious Diseases 2006, 194: 1686-1696. PMID: 17109340, DOI: 10.1086/508750.Peer-Reviewed Original ResearchConceptsHIV-1 RNA levelsCSF HIV-1 RNA levelsPlasma HIV-1 RNA levelsRNA levelsAntiretroviral therapyCSF inflammationCopies/Successful therapyPlasma HIV-1 RNA assaysHIV-1 RNA assaysHIV-1-infected subjectsSuppressive combination antiretroviral therapyDrug resistanceHIV-1 levelsCombination antiretroviral therapyHIV-negative subjectsGenotypic resistance testingFailure of therapyHuman immunodeficiency virusCopies/mLSubset of subjectsActive neurological diseaseCross-sectional analysisVirological suppressionImmunodeficiency virus