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 response
2020
Acute encephalopathy with elevated CSF inflammatory markers as the initial presentation of COVID-19
Farhadian S, Glick LR, Vogels CBF, Thomas J, Chiarella J, Casanovas-Massana A, Zhou J, Odio C, Vijayakumar P, Geng B, Fournier J, Bermejo S, Fauver JR, Alpert T, Wyllie AL, Turcotte C, Steinle M, Paczkowski P, Dela Cruz C, Wilen C, Ko AI, MacKay S, Grubaugh ND, Spudich S, Barakat LA. Acute encephalopathy with elevated CSF inflammatory markers as the initial presentation of COVID-19. BMC Neurology 2020, 20: 248. PMID: 32552792, PMCID: PMC7301053, DOI: 10.1186/s12883-020-01812-2.Peer-Reviewed Original ResearchConceptsInitial presentationCentral nervous system inflammationSARS-CoV-2 infectionCSF inflammatory markersNervous system inflammationCerebrospinal fluid (CSF) cytokinesSeizure-like activityCOVID-19 infectionVirus SARS-CoV-2COVID-19SARS-CoV-2BackgroundCOVID-19Inflammatory markersNeurologic complicationsSystem inflammationImmunocompromised womanNeurologic manifestationsNeurologic symptomsViral neuroinvasionCase presentationWeInfected patientsMental statusRespiratory pathogensConclusionOur findingsInflammation
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 diseasesPersistent 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
Longitudinal Trajectories of Brain Volume and Cortical Thickness in Treated and Untreated Primary Human Immunodeficiency Virus Infection
Sanford R, Ances BM, Meyerhoff DJ, Price RW, Fuchs D, Zetterberg H, Spudich S, Collins DL. Longitudinal Trajectories of Brain Volume and Cortical Thickness in Treated and Untreated Primary Human Immunodeficiency Virus Infection. Clinical Infectious Diseases 2018, 67: 1697-1704. PMID: 29697762, PMCID: PMC6233681, DOI: 10.1093/cid/ciy362.Peer-Reviewed Original ResearchConceptsCombination antiretroviral therapyHuman immunodeficiency virusPrimary HIV infectionChronic HIV infectionCortical thicknessHIV infectionCortical thinningUntreated infectionTemporal lobeBrain volumeImpact of HIVPrimary human immunodeficiency virus (HIV) infectionEarly combination antiretroviral therapyUntreated human immunodeficiency virusHuman immunodeficiency virus (HIV) infectionLongitudinal magnetic resonance imagingImmunodeficiency virus infectionCerebrospinal fluid biomarkersStructural brain changesCortical gray matterMagnetic resonance imagingBrain morphometric measuresCART durationAntiretroviral therapySubcortical atrophy
2017
Blood-Brain Barrier Disruption Is Initiated During Primary HIV Infection and Not Rapidly Altered by Antiretroviral Therapy
Rahimy E, Li FY, Hagberg L, Fuchs D, Robertson K, Meyerhoff DJ, Zetterberg H, Price RW, Gisslén M, Spudich S. Blood-Brain Barrier Disruption Is Initiated During Primary HIV Infection and Not Rapidly Altered by Antiretroviral Therapy. The Journal Of Infectious Diseases 2017, 215: 1132-1140. PMID: 28368497, PMCID: PMC5426376, DOI: 10.1093/infdis/jix013.Peer-Reviewed Original ResearchConceptsPrimary HIV infectionCombination antiretroviral therapyHIV infectionNeurofilament light chainAntiretroviral therapyCreatinine levelsCerebrospinal fluidN-acetylaspartateAbnormal blood-brain barrier (BBB) permeabilityPrimary human immunodeficiency virus (HIV) infectionBlood-brain barrier disruptionHuman immunodeficiency virus (HIV) infectionBlood-brain barrier permeabilityNeuropsychological performanceImmunodeficiency virus infectionParietal gray matterYears of treatmentLongitudinal observational studyCART durationCART initiationMedian intervalNeuronal injuryAlbumin quotientNfL levelsCSF levels
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 factorsInfectionDiagnosis