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
2020
Neuropathogenesis and Neurologic Manifestations of the Coronaviruses in the Age of Coronavirus Disease 2019
Zubair AS, McAlpine LS, Gardin T, Farhadian S, Kuruvilla DE, Spudich S. Neuropathogenesis and Neurologic Manifestations of the Coronaviruses in the Age of Coronavirus Disease 2019. JAMA Neurology 2020, 77: 1018-1027. PMID: 32469387, PMCID: PMC7484225, DOI: 10.1001/jamaneurol.2020.2065.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsCentral nervous systemCoronavirus disease 2019Nervous systemDisease 2019Respiratory syndromeCOVID-19Severe acute respiratory syndrome coronavirus 2Acute respiratory syndrome coronavirus 2Long-term neurologic sequelaeRespiratory syndrome coronavirus 2Middle East respiratory syndromeSevere acute respiratory syndromeClinical neurological complicationsFurther neuropathological studiesBest treatment algorithmImproved clinical outcomesBlood-brain barrierImpairment of consciousnessSyndrome coronavirus 2Peripheral nervous systemAcute respiratory syndromeHuman coronavirus disease 2019Common neurologic complaintsSARS-CoV-2Neurologic sequelae
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 diseasesPredicting Efavirenz Concentrations in the Brain Tissue of HIV‐Infected Individuals and Exploring their Relationship to Neurocognitive Impairment
Srinivas N, Joseph SB, Robertson K, Kincer LP, Menezes P, Adamson L, Schauer AP, Blake KH, White N, Sykes C, Luciw P, Eron JJ, Forrest A, Price R, Spudich S, Swanstrom R, Kashuba A. Predicting Efavirenz Concentrations in the Brain Tissue of HIV‐Infected Individuals and Exploring their Relationship to Neurocognitive Impairment. Clinical And Translational Science 2019, 12: 302-311. PMID: 30675981, PMCID: PMC6510381, DOI: 10.1111/cts.12620.Peer-Reviewed Original ResearchConceptsBrain tissue concentrationsCerebrospinal fluidBrain tissueRhesus macaquesNeurocognitive scoresPK/pharmacodynamic analysesPenetration of antiretroviralsTissue concentrationsExposure-response analysisConcentration-time curveAdult rhesus macaquesCSF AUCEfavirenz concentrationsPlasma AUCPharmacodynamic analysisClinical studiesTissue AUCNeurocognitive impairmentCSF samplesPharmacokinetic dataPK modelingHIVTime pointsAUCNecropsy
2018
Central 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 strategies
2006
Defining and Evaluating HIV-Related Neurodegenerative Disease and Its Treatment Targets: A Combinatorial Approach to Use of Cerebrospinal Fluid Molecular Biomarkers
Gisslen M, Hagberg L, Rosengren L, Brew BJ, Cinque P, Spudich S, Price RW. Defining and Evaluating HIV-Related Neurodegenerative Disease and Its Treatment Targets: A Combinatorial Approach to Use of Cerebrospinal Fluid Molecular Biomarkers. Journal Of Neuroimmune Pharmacology 2006, 2: 112-119. PMID: 18040834, DOI: 10.1007/s11481-006-9035-1.Peer-Reviewed Original ResearchConceptsCNS HIV infectionAIDS dementia complexHIV infectionBrain injuryTreatment targetsCentral nervous system infectionNeurodegenerative diseasesSystemic HIV infectionComorbidities of patientsNervous system infectionAdjuvant treatment approachesCerebrospinal fluid markersRational trial designIntrathecal immunoactivationSystem infectionDementia complexAvailable treatmentsClinical trialsFluid markersTrial designTreatment approachesClinical practiceExperimental therapeuticsPatientsInfection