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 proteomeMedical comorbidities and lower myelin content are associated with poor cognition in young adults with perinatally acquired HIV
Patel P, Prince D, Bolenzius J, Ch’en P, Chiarella J, Kolind S, Vavasour I, Pedersen T, Levendovszky S, Spudich S, Marra C, Paul R. Medical comorbidities and lower myelin content are associated with poor cognition in young adults with perinatally acquired HIV. AIDS 2024, 38: 1932-1939. PMID: 39110577, PMCID: PMC11524773, DOI: 10.1097/qad.0000000000003989.Peer-Reviewed Original ResearchPoor cognitionCognitive impairmentHorizontally acquired HIVMarkers of cognitive reserveAssociated with poorer cognitionRisk factorsCross-sectional studyYoung adultsLower cognitive scoresYears of educationMultiple cognitive domainsExperience cognitive deficitsCognitive domain scoresHIV-uninfected controlsOlder adultsCorticospinal tractCognitive batteryDomain scoresMedical comorbidityCognitive deficitsCognitive domainsMyelin contentCognitive reserveNeuroimaging dataCognitive scoresCentral Nervous System Effects of Early HIV Infection and Consequences of Antiretroviral Therapy Initiation during Acute HIV
Chan P, Spudich S. Central Nervous System Effects of Early HIV Infection and Consequences of Antiretroviral Therapy Initiation during Acute HIV. Viruses 2024, 16: 1082. PMID: 39066244, PMCID: PMC11281648, DOI: 10.3390/v16071082.Peer-Reviewed Original ResearchConceptsEarly HIV infectionCentral nervous systemHIV infectionEffects of early HIV infectionIncrease awareness of HIV infectionCentral nervous system opportunistic infectionsImmediate initiation of antiretroviral therapyInitiation of antiretroviral therapyAwareness of HIV infectionCentral nervous system complicationsCentral nervous system involvementAntiretroviral therapy initiationCentral nervous system effectsLong-term neuroprotectionHIV-associated dementiaOvert clinical manifestationsYears of infectionMulti-organ diseaseNucleic acid testingAcute HIVHIV neuroinvasionHIV RNAAntiretroviral therapyOpportunistic infectionsTherapy initiationTranscobalamin receptor antibodies in autoimmune vitamin B12 central deficiency
Pluvinage J, Ngo T, Fouassier C, McDonagh M, Holmes B, Bartley C, Kondapavulur S, Hurabielle C, Bodansky A, Pai V, Hinman S, Aslanpour A, Alvarenga B, Zorn K, Zamecnik C, McCann A, Asencor A, Huynh T, Browne W, Tubati A, Haney M, Douglas V, Louine M, Cree B, Hauser S, Seeley W, Baranzini S, Wells J, Spudich S, Farhadian S, Ramachandran P, Gillum L, Hales C, Zikherman J, Anderson M, Yazdany J, Smith B, Nath A, Suh G, Flanagan E, Green A, Green R, Gelfand J, DeRisi J, Pleasure S, Wilson M. Transcobalamin receptor antibodies in autoimmune vitamin B12 central deficiency. Science Translational Medicine 2024, 16: eadl3758. PMID: 38924428, PMCID: PMC11520464, DOI: 10.1126/scitranslmed.adl3758.Peer-Reviewed Original ResearchConceptsBlood-brain barrierCerebrospinal fluidNeurological deficitsAutoimmune neurological conditionsCohort of patientsCellular uptake of cobalaminVitamin B12B12 transportCerebrospinal fluid samplesMeasurement of vitamin B12Low-density lipoprotein receptorProgrammable phage displayImmunosuppressive treatmentIn vitro modelNeuropsychiatric lupusImmunomodulatory treatmentReceptor antibodiesClinical improvementUptake of cobalaminB12 deficiencyUnknown etiologyHematopoietic cellsTranscobalamin receptorCentral deficiencyB12 supplementationThe single-cell opioid responses in the context of HIV (SCORCH) consortium
Ament S, Campbell R, Lobo M, Receveur J, Agrawal K, Borjabad A, Byrareddy S, Chang L, Clarke D, Emani P, Gabuzda D, Gaulton K, Giglio M, Giorgi F, Gok B, Guda C, Hadas E, Herb B, Hu W, Huttner A, Ishmam M, Jacobs M, Kelschenbach J, Kim D, Lee C, Liu S, Liu X, Madras B, Mahurkar A, Mash D, Mukamel E, Niu M, O’Connor R, Pagan C, Pang A, Pillai P, Repunte-Canonigo V, Ruzicka W, Stanley J, Tickle T, Tsai S, Wang A, Wills L, Wilson A, Wright S, Xu S, Yang J, Zand M, Zhang L, Zhang J, Akbarian S, Buch S, Cheng C, Corley M, Fox H, Gerstein M, Gummuluru S, Heiman M, Ho Y, Kellis M, Kenny P, Kluger Y, Milner T, Moore D, Morgello S, Ndhlovu L, Rana T, Sanna P, Satterlee J, Sestan N, Spector S, Spudich S, Tilgner H, Volsky D, White O, Williams D, Zeng H. The single-cell opioid responses in the context of HIV (SCORCH) consortium. Molecular Psychiatry 2024, 1-12. PMID: 38879719, DOI: 10.1038/s41380-024-02620-7.Peer-Reviewed Original ResearchContext of human immunodeficiency virusHuman immunodeficiency virusSubstance use disordersOpioid responseAnimal modelsEffects of substance use disordersOpioid pain medicationsPrevalence of co-morbid conditionsChronic pain syndromesStage of diseaseCell typesAffected cell typesCo-morbid conditionsPain syndromeImmunodeficiency virusPain medicationOpioid addictionIncreased riskRisk factorsHuman cohortsDrug addictionBrain tissue collectionBrain cell typesTissue collectionSingle-cell levelPrevalence of detectable HIV-DNA and HIV-RNA in cerebrospinal fluid of youth with perinatal HIV and impaired cognition on antiretroviral therapy
Wagner T, Tierney C, Huang S, Nichols S, Malee K, Montañez N, Coletti A, Spiegel H, Krotje C, Bone F, Wilkins M, Abuogi L, Purswani M, Bearden A, Wiznia A, Agwu A, Chadwick E, Richman D, Gandhi M, Mehta P, Macatangay B, Spector S, Spudich S, Persaud D, Chahroudi A, Team F. Prevalence of detectable HIV-DNA and HIV-RNA in cerebrospinal fluid of youth with perinatal HIV and impaired cognition on antiretroviral therapy. AIDS 2024, 38: 1494-1504. PMID: 38814693, PMCID: PMC11239098, DOI: 10.1097/qad.0000000000003937.Peer-Reviewed Original ResearchCell-free HIV RNAAntiretroviral therapyHIV DNACentral nervous systemDetect HIV DNACerebrospinal fluidHIV RNAPerinatal HIVLong-term virologic suppressionFluid cognition composite scoresSuppressive antiretroviral therapyCerebrospinal fluid cellsHair antiretroviral concentrationsHIV DNA detectionQuantify HIVVirologic suppressionAntiretroviral concentrationsCD4 countCerebrospinal fluid collectionHIV infectionHIV GagPol DNANeurocognitive impairmentCognitive impairmentHIVCase-Control Study of Individuals With Small Fiber Neuropathy After COVID-19
McAlpine L, Zubair A, Joseph P, Spudich S. Case-Control Study of Individuals With Small Fiber Neuropathy After COVID-19. Neurology Neuroimmunology & Neuroinflammation 2024, 11: e200244. PMID: 38630952, PMCID: PMC11087026, DOI: 10.1212/nxi.0000000000200244.Peer-Reviewed Original ResearchConceptsInvasive cardiopulmonary exercise testingSmall fiber neuropathyCase-control studyFiber neuropathySkin biopsiesClinical response to treatmentNeurovascular dysregulationTreated with IVIGRetrospective chart reviewCase-control study of individualsRetrospective cohort studyResponse to treatmentCardiopulmonary exercise testingClass III evidenceMyalgic encephalomyelitis/chronic fatigue syndromeIVIG groupClinical responseNeuropathic symptomsChart reviewIVIGStudy of individualsCohort studyIII evidenceClinical trialsCOVID-19 illnessFocal White Matter Damage in Individuals with Cognitive Impairment After COVID-19 (P11-13.004)
McAlpine L, Nelson A, Chiarella J, Lacadie C, Farhadian S, Constable T, Spudich S. Focal White Matter Damage in Individuals with Cognitive Impairment After COVID-19 (P11-13.004). Neurology 2024, 102 DOI: 10.1212/wnl.0000000000204666.Peer-Reviewed Original ResearchHIV-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 cellsFramingham risk score based vascular outcomes in acute versus chronic HIV cohorts after 6 years of ART
Holroyd K, Han W, Apornpong T, Trautmann L, Gatechompol S, Hiransuthikul A, Ubolyam S, Sacdalan C, Sriplienchan S, Kanaprach R, Kerr S, Avihingsanon A, Spudich S, Chan P. Framingham risk score based vascular outcomes in acute versus chronic HIV cohorts after 6 years of ART. HIV Medicine 2024, 25: 725-736. PMID: 38383057, PMCID: PMC11153003, DOI: 10.1111/hiv.13621.Peer-Reviewed Original ResearchConceptsFramingham risk scoreYears of antiretroviral therapyAcute HIVHigher CD4 countsAntiretroviral therapyChronic HIVCD4 countFollow-upAtherosclerotic cardiovascular diseaseVascular outcomesAssociated with higher body mass indexCardiovascular diseaseRisk scoreHigher body mass indexRisk factorsPrevalence of syphilisVascular agingCD8 T-cell countsMetabolic risk factorsCohort of participantsBody mass indexMultivariate linear regression analysisCardiovascular risk factorsEffect of ART initiationStarted antiretroviral therapyNew approaches for understanding the potential role of microbes in Alzheimer's disease
Whitson H, Banks W, Diaz M, Frost B, Kellis M, Lathe R, Schmader K, Spudich S, Tanzi R, Garden G. New approaches for understanding the potential role of microbes in Alzheimer's disease. Brain Behavior & Immunity - Health 2024, 36: 100743. PMID: 38435720, PMCID: PMC10906156, DOI: 10.1016/j.bbih.2024.100743.Peer-Reviewed Original ResearchAlzheimer's diseaseAD pathologyAntimicrobial protection hypothesisInfluence AD pathologyGene-environment interactionsModel organismsMicrobial organismsMicrobesPotential roleAmyloid accumulationProtection hypothesisAlzheimerImmune cell activationReview new evidencePathological processesCell activationComplex pathological processAmyloidGermOrganizationAlzheimer's Disease Research Center
2023
Characteristics and outcomes of COVID-19 in an early-treated HIV cohort in Thailand
Ocampo F, Paudel M, Sacdalan C, Pinyakorn S, Puttamaswin S, Srieplenchan S, Paul R, Phanuphak N, Chan P, Hsu D, Spudich S. Characteristics and outcomes of COVID-19 in an early-treated HIV cohort in Thailand. Journal Of The Neurological Sciences 2023, 455: 122565. DOI: 10.1016/j.jns.2023.122565.Peer-Reviewed Original ResearchCerebrospinal 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 ageSelf-Reported Neuropsychiatric Post–COVID-19 Condition and CSF Markers of Neuroinflammation
Farhadian S, Reisert H, McAlpine L, Chiarella J, Kosana P, Yoon J, Spudich S. Self-Reported Neuropsychiatric Post–COVID-19 Condition and CSF Markers of Neuroinflammation. JAMA Network Open 2023, 6: e2342741. PMID: 37948085, PMCID: PMC10638645, DOI: 10.1001/jamanetworkopen.2023.42741.Peer-Reviewed Original ResearchCD4dimCD8bright T cells are inversely associated with neuro-inflammatory markers among people with HIV
Albalawi Y, Shull T, Virdi A, Subra C, Mitchell J, Slike B, Jian N, Krebs S, Sacdalan C, Ratnaratorn N, Hsu D, Phanuphak N, Spudich S, Trautmann L, Al-Harthi L. CD4dimCD8bright T cells are inversely associated with neuro-inflammatory markers among people with HIV. AIDS 2023, 38: 1-7. PMID: 37792358, PMCID: PMC10715695, DOI: 10.1097/qad.0000000000003743.Peer-Reviewed Original ResearchConceptsCombination antiretroviral therapyT cellsWeeks 0CD4-CD8Cerebrospinal fluidImmune activationSoluble markersSuppressive combination antiretroviral therapyPeripheral blood T cellsNeuro-inflammatory markersSubset of CD8Anti-inflammatory propertiesBlood T cellsConfidence intervalsPlasma of peopleT-cell typeCART initiationCSF neopterinPlasma RANTESAntiretroviral therapyWeek 24IP-10IL-6Lumbar punctureIL-8Antiretroviral Therapy Intensification for Neurocognitive Impairment in Human Immunodeficiency Virus
Letendre S, Chen H, McKhann A, Roa J, Vecchio A, Daar E, Berzins B, Hunt P, Marra C, Campbell T, Coombs R, Ma Q, Swaminathan S, Macatangay B, Morse G, Miller T, Rusin D, Greninger A, Ha B, Alston-Smith B, Robertson K, Paul R, Spudich S, Team T. Antiretroviral Therapy Intensification for Neurocognitive Impairment in Human Immunodeficiency Virus. Clinical Infectious Diseases 2023, 77: 866-874. PMID: 37183889, PMCID: PMC10506779, DOI: 10.1093/cid/ciad265.Peer-Reviewed Original ResearchConceptsAntiretroviral therapyART intensificationNeurocognitive impairmentWeek 48Z-scoreAntiretroviral therapy intensificationPersistent HIV replicationPlacebo-controlled trialPlasma HIV RNASuppressive antiretroviral therapyAge 52 yearsBody mass indexHuman immunodeficiency virusCopies/mLTotal Z-scoreBaseline z-scoresCentral nervous systemDual placeboEfavirenz useTherapy intensificationHIV RNAStudy drugAdverse eventsSymptomatic HIVPrimary outcomeVascular Age and Cognitive Outcomes in an Acute HIV Cohort After Six Years of ART (P13-10.001)
Holroyd K, Sacdalan C, Pinyakorn S, Unsombut V, Sriplienchan S, Paul R, Panauphak N, Hsu D, Vasan S, Spudich S, Chan P. Vascular Age and Cognitive Outcomes in an Acute HIV Cohort After Six Years of ART (P13-10.001). Neurology 2023, 100 DOI: 10.1212/wnl.0000000000201802.Peer-Reviewed Original ResearchBiotypes of Central Nervous System Complications in People With Human Immunodeficiency Virus: Virology, Immunology, and Neuropathology
Joseph S, Gianella S, Burdo T, Cinque P, Gisslen M, Letendre S, Nath A, Morgello S, Ndhlovu L, Spudich S. Biotypes of Central Nervous System Complications in People With Human Immunodeficiency Virus: Virology, Immunology, and Neuropathology. The Journal Of Infectious Diseases 2023, 227: s3-s15. PMID: 36930640, PMCID: PMC10022721, DOI: 10.1093/infdis/jiac370.Peer-Reviewed Original ResearchConceptsHuman immunodeficiency virusCentral nervous system complicationsNervous system complicationsAntiretroviral therapySystem complicationsImmunodeficiency virusMental health disordersMild cognitive impairmentCNS complicationsMultifactorial pathogenesisViral suppressionHeterogeneity of mechanismsCNS diseaseNeuropathological dataEffective treatmentHealth disordersCognitive impairmentPreventive interventionsComplicationsImmunologyVirusWorking GroupVirologyNeuroHIVNeuropathologyRebound HIV-1 in cerebrospinal fluid after antiviral therapy interruption is mainly clonally amplified R5 T cell-tropic virus
Kincer L, Joseph S, Gilleece M, Hauser B, Sizemore S, Zhou S, Di Germanio C, Zetterberg H, Fuchs D, Deeks S, Spudich S, Gisslen M, Price R, Swanstrom R. Rebound HIV-1 in cerebrospinal fluid after antiviral therapy interruption is mainly clonally amplified R5 T cell-tropic virus. Nature Microbiology 2023, 8: 260-271. PMID: 36717718, PMCID: PMC10201410, DOI: 10.1038/s41564-022-01306-6.Peer-Reviewed Original ResearchConceptsCentral nervous systemT cell-tropic virusesInfected T cellsCerebrospinal fluidAntiretroviral therapyHIV-1Rebound virusViral loadT cellsMacrophage-tropic HIV-1CSF viral loadSuppressive antiretroviral therapyHIV-1 reservoirMacrophage-tropic virusesHigh viral loadWhite blood cellsTherapy interruptionLatent reservoirLymphoid systemNervous systemSystemic infectionVirus replicationBlood cellsTransient influxVirus