2022
HIV viral transcription and immune perturbations in the CNS of people with HIV despite ART
Farhadian SF, Lindenbaum O, Zhao J, Corley MJ, Im Y, Walsh H, Vecchio A, Garcia-Milian R, Chiarella J, Chintanaphol M, Calvi R, Wang G, Ndhlovu LC, Yoon J, Trotta D, Ma S, Kluger Y, Spudich S. HIV viral transcription and immune perturbations in the CNS of people with HIV despite ART. JCI Insight 2022, 7: e160267. PMID: 35801589, PMCID: PMC9310520, DOI: 10.1172/jci.insight.160267.Peer-Reviewed Original ResearchConceptsCerebrospinal fluidHIV infectionHIV-1-infected cellsCNS viral persistenceCentral memory CD4T-cell abnormalitiesHIV-1 RNAMicroglia-like cellsT cell activationSystemic viral suppressionAbnormal CD8HIV neuropathogenesisViral suppressionMemory CD4CNS reservoirsImmune perturbationsExperience elevated ratesNeuroimmune effectsPeripheral bloodNeurological impairmentViral persistenceT cellsCell abnormalitiesUninfected controlsCell activation
2020
Neuropsychiatric outcomes before and after switching to dolutegravir-based therapy in an acute HIV cohort
Chan P, Goh O, Kroon E, Colby D, Sacdalan C, Pinyakorn S, Prueksakaew P, Reiss P, Ananworanich J, Valcour V, Spudich S, Paul R. Neuropsychiatric outcomes before and after switching to dolutegravir-based therapy in an acute HIV cohort. AIDS Research And Therapy 2020, 17: 1. PMID: 31907064, PMCID: PMC6945418, DOI: 10.1186/s12981-019-0257-8.Peer-Reviewed Original ResearchConceptsPatient Health Questionnaire-9Acute HIV infectionWeeks of ARTAntiretroviral therapyPHQ-9 scoresDTG-based antiretroviral therapyLower PHQ-9 scoresDolutegravir-based therapyDTG-based regimenNeuropsychiatric adverse eventsPlasma viral suppressionFirst-line treatmentPre-existing depressionLeast moderate depressionModerate-severe depressionModerate depression symptomsPercentage of participantsDTG useViral suppressionHIV cohortMedian durationAdverse eventsHIV infectionHighest quartileMultivariable analysis
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 cellsLongitudinal 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
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 Research
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 courseCerebral metabolite changes prior to and after antiretroviral therapy in primary HIV infection
Young AC, Yiannoutsos CT, Hegde M, Lee E, Peterson J, Walter R, Price RW, Meyerhoff DJ, Spudich S. Cerebral metabolite changes prior to and after antiretroviral therapy in primary HIV infection. Neurology 2014, 83: 1592-1600. PMID: 25261502, PMCID: PMC4223087, DOI: 10.1212/wnl.0000000000000932.Peer-Reviewed Original ResearchMeSH KeywordsAdultAnti-Retroviral AgentsCerebrumChronic DiseaseFemaleHIV InfectionsHumansLongitudinal StudiesMagnetic Resonance SpectroscopyMaleMiddle AgedConceptsPrimary HIV infectionParietal gray matterInitiation of ARTMI/CrFrontal white matterAntiretroviral therapyGlu/CrCho/CrHIV infectionBasal gangliaWhite matterGray matterN-acetylaspartateT proton magnetic resonance spectroscopyCerebral metabolite changesEarly ART initiationTreatment-naive participantsEarly antiretroviral therapyLevels of glutamateNAA/CrProton magnetic resonance spectroscopyCholine-containing metabolitesMagnetic resonance spectroscopyART initiationHigh-field magnetic resonance spectroscopyLongitudinal 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
2008
Enfuvirtide Cerebrospinal Fluid (CSF) Pharmacokinetics and Potential use in Defining CSF HIV-1 Origin
Price RW, Parham R, Kroll JL, Wring SA, Baker B, Sailstad J, Hoh R, Liegler T, Spudich S, Kuritzkes DR, Deeks SG. Enfuvirtide Cerebrospinal Fluid (CSF) Pharmacokinetics and Potential use in Defining CSF HIV-1 Origin. Antiviral Therapy 2008, 13: 369-374. PMID: 18572749, PMCID: PMC2699482, DOI: 10.1177/135965350801300312.Peer-Reviewed Original ResearchConceptsCentral nervous systemCerebrospinal fluidCSF samplesCSF HIV-1 RNAHIV-1-infected individualsHIV-negative individualsCerebrospinal fluid pharmacokineticsHIV-1 RNAHuman central nervous systemPlasma samplesHIV-1 replicationCNS drug exposureHIV-1 quasispeciesUse of enfuvirtideResistance-associated mutationsLocal therapeutic effectCNS virusV38A mutationGp41 coding regionCSF pharmacokineticsDrug exposurePlasma concentrationsTherapeutic effectNervous systemClinical setting
2005
HIV-1 Chemokine Coreceptor Utilization in Paired Cerebrospinal Fluid and Plasma Samples: A Survey of Subjects with Viremia
Spudich SS, Huang W, Nilsson AC, Petropoulos CJ, Liegler TJ, Whitcomb JM, Price RW. HIV-1 Chemokine Coreceptor Utilization in Paired Cerebrospinal Fluid and Plasma Samples: A Survey of Subjects with Viremia. The Journal Of Infectious Diseases 2005, 191: 890-898. PMID: 15717264, DOI: 10.1086/428095.Peer-Reviewed Original ResearchConceptsCerebrospinal fluidImmunodeficiency syndrome dementia complexCD4 T-cell countHuman immunodeficiency virus type 1 (HIV-1) entryMixture of R5Paired Cerebrospinal FluidT-cell countsPlasma samplesSurvey of subjectsHIV-1 populationsAdvanced immunodeficiencyCoreceptor utilizationInhibitor therapyPrincipal coreceptorR5 phenotypeX4 virusesDementia complexR5 virusesR5 tropismChemokine receptorsInfection pathogenesisCell countViral tropismDiscordant tropismCell tropism