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 infectionChanges in cerebrospinal fluid proteins across the spectrum of untreated and treated chronic HIV-1 infection
Hu Z, Cinque P, Dravid A, Hagberg L, Yilmaz A, Zetterberg H, Fuchs D, Gostner J, Blennow K, Spudich S, Kincer L, Zhou S, Joseph S, Swanstrom R, Price R, Gisslén M. Changes in cerebrospinal fluid proteins across the spectrum of untreated and treated chronic HIV-1 infection. PLOS Pathogens 2024, 20: e1012470. PMID: 39316609, PMCID: PMC11469498, DOI: 10.1371/journal.ppat.1012470.Peer-Reviewed Original ResearchConceptsHIV-1 infectionHIV-associated dementiaCerebrospinal fluidCerebrospinal fluid proteinCerebrospinal fluid HIV-1 RNAImpact of HIV-1 infectionTreating chronic HIV-1 infectionChronic HIV-1 infectionHIV-1 RNAHIV-1 progressionTreat chronic infectionsInflammatory cell lineagesNeurofilament light chain proteinCSF escapeChronic infectionHIV-1Light chain proteinProtein changesClinical centersCNS injuryCSF proteinClinical informationCell lineagesInfectionCerebrospinal fluid proteomeHIV-1–infected T cell clones are shared across cerebrospinal fluid and blood during ART
Wang M, Yoon J, Reisert H, Das B, Orlinick B, Chiarella J, Halvas E, Mellors J, Pang A, Barakat L, Fikrig M, Cyktor J, Kluger Y, Spudich S, Corley M, Farhadian S. HIV-1–infected T cell clones are shared across cerebrospinal fluid and blood during ART. JCI Insight 2024, 9: e176208. PMID: 38587074, PMCID: PMC11128194, DOI: 10.1172/jci.insight.176208.Peer-Reviewed Original ResearchConceptsT cell clonesT cell receptorCerebrospinal fluidT cellsHIV-1Infected T-cell clonesCentral memory T cellsCD4 T-cell clonesDetectable HIV RNAMemory T cellsHIV-1 RNAInfected T cellsCNS reservoirsHIV persistenceHIV reservoirHIV RNAHIV cureReservoir cellsPWHTissue compartmentsBloodCNSUninfected controlsCD4Infected cells
2023
Cerebrospinal fluid pleocytosis is associated with HIV-1 neuroinvasion during acute infection
Chan P, Moreland S, Sacdalan C, Kroon E, Colby D, Sriplienchan S, Pinyakorn S, Phanuphak N, Jagodzinski L, Valcour V, Vasan S, Paul R, Trautmann L, Spudich S, Team O. Cerebrospinal fluid pleocytosis is associated with HIV-1 neuroinvasion during acute infection. AIDS 2023, 38: 373-378. PMID: 37916464, PMCID: PMC10842649, DOI: 10.1097/qad.0000000000003777.Peer-Reviewed Original ResearchCSF HIV-1 RNAWhite blood cell countHIV-1 RNAAcute HIV infectionCp/mLCSF pleocytosisCSF samplesLower plasmaCerebrospinal fluid white blood cell countMedian CSF white blood cell countStage ICSF white blood cell countDetectable HIV-1 RNAFiebig stage IIIFiebig stages ICerebrospinal fluid pleocytosisT-cell countsAcute retroviral syndromeHigh viral loadBlood cell countCells/Blood CD4Acute infectionHIV infectionMedian age
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 activationSingle-cell multiomics reveals persistence of HIV-1 in expanded cytotoxic T cell clones
Collora JA, Liu R, Pinto-Santini D, Ravindra N, Ganoza C, Lama JR, Alfaro R, Chiarella J, Spudich S, Mounzer K, Tebas P, Montaner LJ, van Dijk D, Duerr A, Ho YC. Single-cell multiomics reveals persistence of HIV-1 in expanded cytotoxic T cell clones. Immunity 2022, 55: 1013-1031.e7. PMID: 35320704, PMCID: PMC9203927, DOI: 10.1016/j.immuni.2022.03.004.Peer-Reviewed Original ResearchConceptsHIV-1 eradicationHIV-1 RNAHIV-1Effector memory Th1 cellsHIV-1-infected individualsHIV-1-infected CD4Clonal expansionCell clonesMemory Th1 cellsCell clonal expansionPersistent antigenAntiretroviral therapyViral suppressionCytotoxic CD4Cytotoxic TTh1 cellsAntigen stimulationClonal expansion dynamicsUninfected individualsSurface protein expressionTNF responseUnstimulated conditionsTCR sequencesProtein expressionCD4
2021
Clinical and laboratory impact of concomitant syphilis infection during acute HIV
Chan P, Colby D, Kroon E, Sacdalan C, Pinyakorn S, Paul R, Robb M, Valcour V, Ananworanich J, Marra C, Spudich S. Clinical and laboratory impact of concomitant syphilis infection during acute HIV. HIV Medicine 2021, 22: 502-511. PMID: 33728759, DOI: 10.1111/hiv.13079.Peer-Reviewed Original ResearchConceptsAcute HIV-1T lymphocyte levelsVenereal Disease Research LaboratoryUntreated syphilisHistory of syphilisHIV-1Higher plasma HIV-1 RNACD4 T-lymphocyte levelsPlasma HIV-1 RNAHIV-1 RNA levelsCognitive performanceCD4 T lymphocytesHIV-1 infectionHIV-1 RNAImpaired cognitive performanceAcute HIVAHI participantsFiebig stagesIncident syphilisPrior syphilisSerum TreponemaSyphilis infectionChronic infectionDisease measuresSyphilis status
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 treatmentCentral Nervous System Safety During Brief Analytic Treatment Interruption of Antiretroviral Therapy Within 4 Human Immunodeficiency Virus Remission Trials: An Observational Study in Acutely Treated People Living With Human Immunodeficiency Virus
Hellmuth J, Muccini C, Colby DJ, Kroon E, de Souza M, Crowell TA, Chan P, Sacdalan C, Intasan J, Benjapornpong K, Tipsuk S, Puttamaswin S, Chomchey N, Valcour V, Sarnecki M, Tomaka F, Krebs SJ, Slike BM, Jagodzinski LL, Dumrongpisutikul N, Sailasuta N, Samboju V, Michael NL, Robb ML, Vasan S, Ananworanich J, Phanuphak P, Phanuphak N, Paul R, Spudich S. Central Nervous System Safety During Brief Analytic Treatment Interruption of Antiretroviral Therapy Within 4 Human Immunodeficiency Virus Remission Trials: An Observational Study in Acutely Treated People Living With Human Immunodeficiency Virus. Clinical Infectious Diseases 2020, 73: e1885-e1892. PMID: 32916708, PMCID: PMC8492357, DOI: 10.1093/cid/ciaa1344.Peer-Reviewed Original ResearchConceptsAnalytic treatment interruptionHuman immunodeficiency virusAntiretroviral therapyCentral nervous systemRemission trialsDiffusion tensor imagingTreatment interruptionMedian timeImmunodeficiency virusCentral nervous system safetyCSF HIV-1 RNAAdverse CNS effectsAcute HIV infectionImmune activation markersPlasma viral loadHIV-1 RNAMedian participant ageCerebrospinal fluid samplingCognitive performanceHIV remission trialsBrain diffusion tensor imagingMagnetic resonance spectroscopyART resumptionCNS safetyMild worseningFeasibility and safety of research sigmoid colon biopsy in a cohort of Thai men who have sex with men with acute HIV-1
Chintanaphol M, Sacdalan C, Pinyakorn S, Rerknimitr R, Ridtitid W, Prueksapanich P, Sereti I, Schuetz A, Crowell TA, Colby DJ, Robb ML, Phanuphak N, Ananworanich J, Spudich SS, Kroon E. Feasibility and safety of research sigmoid colon biopsy in a cohort of Thai men who have sex with men with acute HIV-1. Journal Of Virus Eradication 2020, 6: 7-10. PMID: 32175085, PMCID: PMC7043900, DOI: 10.1016/s2055-6640(20)30011-x.Peer-Reviewed Original ResearchAcute HIV-1 infectionGut-associated lymphoid tissueHIV-1 reservoirSigmoid colon biopsiesAdverse eventsAE riskSigmoid colonColon biopsiesHIV-1CD4 T-cell depletionCD4 T-cell countAcute HIV-1Mild rectal bleedingAdverse event incidenceT-cell countsHigh viral replicationT-cell depletionHIV-1 infectionHIV-1 RNATime of biopsyIncidence rate ratiosRectal bleedingAbdominal discomfortEvent incidenceViral load
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 cells
2013
Single-copy assay quantification of HIV-1 RNA in paired cerebrospinal fluid and plasma samples from elite controllers
Dahl V, Peterson J, Spudich S, Lee E, Shacklett BL, Price RW, Palmer S. Single-copy assay quantification of HIV-1 RNA in paired cerebrospinal fluid and plasma samples from elite controllers. AIDS 2013, 27: 1145-1149. PMID: 23211774, PMCID: PMC4004626, DOI: 10.1097/qad.0b013e32835cf235.Peer-Reviewed Original ResearchConceptsHIV-1 RNACentral nervous systemHIV-1 RNA quantificationElite controllersCerebrospinal fluidPlasma samplesCSF samplesHIV-1 RNA concentrationsHIV-1-infected individualsConcurrent plasma samplesSingle-copy assayRNA quantificationAntiretroviral therapyCopies/HIV-1Rare subsetNervous systemRNA concentrationClinical assaysSensitive assayAssaysRNATherapyInfectionBlood
2011
Raltegravir Treatment Intensification Does Not Alter Cerebrospinal Fluid HIV-1 Infection or Immunoactivation in Subjects on Suppressive Therapy
Dahl V, Lee E, Peterson J, Spudich SS, Leppla I, Sinclair E, Fuchs D, Palmer S, Price RW. Raltegravir Treatment Intensification Does Not Alter Cerebrospinal Fluid HIV-1 Infection or Immunoactivation in Subjects on Suppressive Therapy. The Journal Of Infectious Diseases 2011, 204: 1936-1945. PMID: 22021620, PMCID: PMC3209817, DOI: 10.1093/infdis/jir667.Peer-Reviewed Original ResearchConceptsHIV-1 RNA levelsHIV-1 RNAImmune activationRaltegravir intensificationRNA levelsPlasma human immunodeficiency virus type 1 (HIV-1) RNACSF HIV-1 RNA levelsMedian HIV-1 RNA levelT-cell surface antigen expressionHuman immunodeficiency virus type 1 (HIV-1) RNAOpen-label pilot studySingle-copy assayHIV RNA levelsCerebrospinal fluid infectionHIV-1 infectionCentral nervous systemBaseline viral suppressionSurface antigen expressionT cell activationCSF neopterinIntrathecal immunoactivationSuppressive therapyAntiretroviral therapyTreatment intensificationViral suppressionMinocycline fails to modulate cerebrospinal fluid HIV infection or immune activation in chronic untreated HIV-1 infection: results of a pilot study
Ho EL, Spudich SS, Lee E, Fuchs D, Sinclair E, Price RW. Minocycline fails to modulate cerebrospinal fluid HIV infection or immune activation in chronic untreated HIV-1 infection: results of a pilot study. AIDS Research And Therapy 2011, 8: 17. PMID: 21569420, PMCID: PMC3117676, DOI: 10.1186/1742-6405-8-17.Peer-Reviewed Original ResearchCerebrospinal fluidHIV infectionImmune activationPilot studyCSF white blood cell countBlood HIV-1 RNAChronic untreated HIV infectionUntreated HIV-1 infectionWhite blood cell countCell surface activation markersCNS HIV infectionUntreated HIV infectionHIV-1 infectionHIV-1 RNABlood cell countBlood T lymphocytesConclusionsThis pilot studyBlood neopterinCSF CCL2Adjuvant therapyAntiretroviral therapyViremic subjectsActivation markersBlood biomarkersBrain injury
2010
HIV-1 Viral Escape in Cerebrospinal Fluid of Subjects on Suppressive Antiretroviral Treatment
Edén A, Fuchs D, Hagberg L, Nilsson S, Spudich S, Svennerholm B, Price RW, Gisslén M. HIV-1 Viral Escape in Cerebrospinal Fluid of Subjects on Suppressive Antiretroviral Treatment. The Journal Of Infectious Diseases 2010, 202: 1819-1825. PMID: 21050119, PMCID: PMC3052942, DOI: 10.1086/657342.Peer-Reviewed Original ResearchConceptsHIV-1 RNAAntiretroviral therapy regimensCerebrospinal fluidViral escapeTherapy regimensPlasma human immunodeficiency virus type 1 (HIV-1) RNACSF HIV-1 RNAHuman immunodeficiency virus type 1 (HIV-1) RNACentral nervous system infectionCSF neopterin levelsCSF viral escapeHigher CSF neopterinIntrathecal immune activationPrevious treatment interruptionsSuppressive antiretroviral treatmentAtazanavir/ritonavirLopinavir/ritonavirNervous system infectionCSF virusNew treatment combinationsCopies/mLEnzyme-linked immunosorbentPolymerase chain reaction assaysCSF escapeCSF neopterinCerebrospinal 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
2008
Failure of atorvastatin to modulate CSF HIV-1 infection
Probasco JC, Spudich SS, Critchfield J, Lee E, Lollo N, Deeks SG, Price RW. Failure of atorvastatin to modulate CSF HIV-1 infection. Neurology 2008, 71: 521-524. PMID: 18695163, PMCID: PMC2676982, DOI: 10.1212/01.wnl.0000325006.84658.e7.Peer-Reviewed Original ResearchConceptsHIV-1 infectionHIV-1 RNA levelsT-cell countsCell countIntrathecal immunoactivationNeopterin concentrationsBlood lipidsBlood HIV-1 RNA levelCSF HIV-1 RNA levelsCSF white blood cell countCNS HIV-1 infectionSystemic HIV-1 infectionSingle-arm pilot studyWhite blood cell countPilot studyAntiretroviral-naïve subjectsCells/mulRNA levelsUntreated systemic infectionT-lymphocyte countsSmall uncontrolled studiesEffect of atorvastatinHMG-CoA reductase inhibitorsWeeks of treatmentHIV-1 RNAAntiretroviral Treatment Effect on Immune Activation Reduces Cerebrospinal Fluid HIV-1 Infection
Sinclair E, Ronquillo R, Lollo N, Deeks SG, Hunt P, Yiannoutsos CT, Spudich S, Price RW. Antiretroviral Treatment Effect on Immune Activation Reduces Cerebrospinal Fluid HIV-1 Infection. JAIDS Journal Of Acquired Immune Deficiency Syndromes 2008, 47: 544-552. PMID: 18362693, PMCID: PMC3480328, DOI: 10.1097/qai.0b013e318162754f.Peer-Reviewed Original ResearchConceptsPlasma HIV-1 RNACD8 T cell activationHIV-1 RNACSF HIV-1 RNA levelsHIV-1 RNA levelsT cell activationWhite blood cellsHIV-1 concentrationsAntiretroviral therapyHIV-1 infectionCerebrospinal fluidCD8 activationCSF neopterinViremic groupImmune activationCopies/HIV-1CD38/HLA-DR expressionCSF HIV-1 RNA concentrationsHIV-1-infected subjectsSystemic HIV-1 infectionHIV-1 RNA concentrationsHuman leukocyte antigen-DRCSF white blood cellsCoexpression of CD38Enfuvirtide 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 settingPersistent Intrathecal Immune Activation in HIV-1-Infected Individuals on Antiretroviral Therapy
Yilmaz A, Price RW, Spudich S, Fuchs D, Hagberg L, Gisslén M. Persistent Intrathecal Immune Activation in HIV-1-Infected Individuals on Antiretroviral Therapy. JAIDS Journal Of Acquired Immune Deficiency Syndromes 2008, 47: 168-173. PMID: 17971711, PMCID: PMC2628632, DOI: 10.1097/qai.0b013e31815ace97.Peer-Reviewed Original ResearchConceptsCSF neopterin levelsHIV-1-infected patientsHIV-1-infected individualsCSF neopterin concentrationsCSF viral loadIntrathecal immune activationAntiretroviral therapyHIV-1 RNACopies/mLNeopterin levelsViral loadNeopterin concentrationsImmune activationCSF HIV-1 RNA loadMost HIV-1-infected individualsPlasma HIV-1 RNA levelsCerebrospinal fluid (CSF) neopterin levelsQuantitative HIV-1 RNAHIV-1 RNA levelsHIV-1 RNA loadCell-mediated immune responsesHIV-1 RNA quantificationHIV-1 concentrationsStable antiretroviral therapySuppressive antiretroviral therapy