2024
Medical comorbidities and lower myelin content are associated with poor cognition in young adults with perinatally acquired HIV.
Patel P, Prince D, Bolenzius J, Chen 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 PMID: 39110577, 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 scoresFocal 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 cells
2022
OP 4.5 – 00101 Comparative single-cell transcriptome and TCR profiling of HIV infected cells in the blood and cerebrospinal fluid of PLWH before and after ART
Wang M, Corley M, Yoon J, Chiarella J, Cyktor J, Spudich S, Kluger Y, Farhadian S. OP 4.5 – 00101 Comparative single-cell transcriptome and TCR profiling of HIV infected cells in the blood and cerebrospinal fluid of PLWH before and after ART. Journal Of Virus Eradication 2022, 8: 100205. DOI: 10.1016/j.jve.2022.100205.Peer-Reviewed Original ResearchHIV 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
Preliminary In Vivo Evidence of Reduced Synaptic Density in Human Immunodeficiency Virus (HIV) Despite Antiretroviral Therapy
Weiss JJ, Calvi R, Naganawa M, Toyonaga T, Farhadian SF, Chintanaphol M, Chiarella J, Zheng MQ, Ropchan J, Huang Y, Pietrzak RH, Carson RE, Spudich S. Preliminary In Vivo Evidence of Reduced Synaptic Density in Human Immunodeficiency Virus (HIV) Despite Antiretroviral Therapy. Clinical Infectious Diseases 2021, 73: 1404-1411. PMID: 34050746, PMCID: PMC8528400, DOI: 10.1093/cid/ciab484.Peer-Reviewed Original ResearchConceptsHuman immunodeficiency virusAntiretroviral therapySynaptic densityMagnetic resonance imagingMale PLWHImmunodeficiency virusUnderwent magnetic resonance imagingPositron emission tomographicCross-sectional pilotHIV neuropathogenesisViral suppressionCommon complicationSynaptic injuryNeurological impairmentDynamic biomarkersPLWHTherapeutic studiesCortical areasMotor coordinationPathological hallmarkPET scanningPromising biomarkerTherapeutic interventionsResonance imagingPegboard performanceDivergent and self-reactive immune responses in the CNS of COVID-19 patients with neurological symptoms
Song E, Bartley CM, Chow RD, Ngo TT, Jiang R, Zamecnik CR, Dandekar R, Loudermilk RP, Dai Y, Liu F, Sunshine S, Liu J, Wu W, Hawes IA, Alvarenga BD, Huynh T, McAlpine L, Rahman NT, Geng B, Chiarella J, Goldman-Israelow B, Vogels CBF, Grubaugh ND, Casanovas-Massana A, Phinney BS, Salemi M, Alexander JR, Gallego JA, Lencz T, Walsh H, Wapniarski AE, Mohanty S, Lucas C, Klein J, Mao T, Oh J, Ring A, Spudich S, Ko AI, Kleinstein SH, Pak J, DeRisi JL, Iwasaki A, Pleasure SJ, Wilson MR, Farhadian SF. Divergent and self-reactive immune responses in the CNS of COVID-19 patients with neurological symptoms. Cell Reports Medicine 2021, 2: 100288. PMID: 33969321, PMCID: PMC8091032, DOI: 10.1016/j.xcrm.2021.100288.Peer-Reviewed Original ResearchNeurological symptomsImmune responseCerebrospinal fluidAnti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodiesCOVID-19Self-reactive immune responsesSARS-CoV-2 antibodiesCompartmentalized immune responseCSF immunoglobulin GRole of autoimmunityCOVID-19 patientsB cell responsesCoronavirus disease 2019Immune surveyNeurologic sequelaePulmonary infectionBrain infectionSerum antibodiesDisease 2019Monoclonal antibody targetsAnimal modelsTarget epitopesCell activationCell responsesSingle-cell RNA sequencing
2020
Determinants of suboptimal CD4+ T cell recovery after antiretroviral therapy initiation in a prospective cohort of acute HIV‐1 infection
Handoko R, Colby DJ, Kroon E, Sacdalan C, de Souza M, Pinyakorn S, Prueksakaew P, Munkong C, Ubolyam S, Akapirat S, Chiarella J, Krebs S, Sereti I, Valcour V, Paul R, Michael NL, Phanuphak N, Ananworanich J, Spudich S, Team T. Determinants of suboptimal CD4+ T cell recovery after antiretroviral therapy initiation in a prospective cohort of acute HIV‐1 infection. Journal Of The International AIDS Society 2020, 23: e25585. PMID: 32949118, PMCID: PMC7507109, DOI: 10.1002/jia2.25585.Peer-Reviewed Original ResearchConceptsAcute HIV infectionCD4/CD8 ratioSuboptimal CD4 recoveryAntiretroviral therapyCD4 countImmune recoveryCD4 recoveryCD8 ratioStudy visitAcute HIV-1 infectionPre-ART CD4 countLower CD8 countsPlasma viral suppressionSuboptimal immune recoveryAntiretroviral therapy initiationT-cell countsT-cell recoveryHIV-1 infectionCopies/mLLower IL-6Cells/ART initiationCD4 rateCD8 countsChronic HIVFilgotinib suppresses HIV-1-driven gene transcription by inhibiting HIV-1 splicing and T cell activation
Yeh YJ, Jenike KM, Calvi RM, Chiarella J, Hoh R, Deeks SG, Ho YC. Filgotinib suppresses HIV-1-driven gene transcription by inhibiting HIV-1 splicing and T cell activation. Journal Of Clinical Investigation 2020, 130: 4969-4984. PMID: 32573496, PMCID: PMC7456222, DOI: 10.1172/jci137371.Peer-Reviewed Original ResearchConceptsHIV-1 reactivationHIV-1-infected cellsT cell activationImmune activationHIV-1-induced immune activationCell activationHIV-1 RNA transcriptionHIV-1-infected individualsDrug screensEffective antiretroviral therapyHIV-1 transcriptionFilgotinib treatmentImmune exhaustionAntiretroviral therapyCell line modelsCancer-related gene expressionHIV-1 splicingViral antigensT cellsDrug treatmentHigh-throughput drug screensJAK inhibitorsFilgotinibDruggable targetsDrug candidatesAcute 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 findingsInflammationSingle-cell transcriptional landscapes reveal HIV-1–driven aberrant host gene transcription as a potential therapeutic target
Liu R, Yeh YJ, Varabyou A, Collora JA, Sherrill-Mix S, Talbot CC, Mehta S, Albrecht K, Hao H, Zhang H, Pollack RA, Beg SA, Calvi RM, Hu J, Durand CM, Ambinder RF, Hoh R, Deeks SG, Chiarella J, Spudich S, Douek DC, Bushman FD, Pertea M, Ho YC. Single-cell transcriptional landscapes reveal HIV-1–driven aberrant host gene transcription as a potential therapeutic target. Science Translational Medicine 2020, 12 PMID: 32404504, PMCID: PMC7453882, DOI: 10.1126/scitranslmed.aaz0802.Peer-Reviewed Original ResearchConceptsHost gene transcriptionGene transcriptionLong terminal repeatHIV-1 reactivationCellular factorsIntegration sitesNonsense-mediated RNA decaySingle-cell transcriptional landscapePotential therapeutic targetSingle-cell transcriptome analysisHIV-1-host interactionsHIV-1HIV-1 promoterTherapeutic targetHIV-1 5' long terminal repeatRNA decayTranscriptional landscapeHIV-1-infected individualsHIV-1-infected cellsTranscriptome analysisAberrant transcriptionRNA transcriptionHost RNACellular survivalTranscription pathway
2019
Exosomal MicroRNAs Associate With Neuropsychological Performance in Individuals With HIV Infection on Antiretroviral Therapy.
OʼMeara T, Kong Y, Chiarella J, Price RW, Chaudhury R, Liu X, Spudich S, Robertson K, Emu B, Lu L. Exosomal MicroRNAs Associate With Neuropsychological Performance in Individuals With HIV Infection on Antiretroviral Therapy. JAIDS Journal Of Acquired Immune Deficiency Syndromes 2019, 82: 514-522. PMID: 31714431, PMCID: PMC6857839, DOI: 10.1097/qai.0000000000002187.Peer-Reviewed Original ResearchConceptsCombination antiretroviral therapyNeuropsychological performanceAntiretroviral therapyViral suppressionHIV infectionNeurocognitive dysfunctionExo-miRNAsEarly infection groupCentral nervous systemSystemic viral suppressionTyrosine receptor kinaseInfection groupChronic infectionPLWHCross-sectional examinationNervous systemEarly infectionNeuropsychological scoresInfectionConsistent findingNeuropsychological batteryHIVNeurodegeneration pathwaysDysfunctionTherapyMarkers of CNS Injury in Adults Living With HIV With CSF HIV Not Detected vs Detected <20 Copies/mL
Farhadian SF, Mistry H, Kirchwey T, Chiarella J, Calvi R, Chintanaphol M, Patel P, Landry ML, Robertson K, Spudich SS. Markers of CNS Injury in Adults Living With HIV With CSF HIV Not Detected vs Detected <20 Copies/mL. Open Forum Infectious Diseases 2019, 6: ofz528. PMID: 31893212, PMCID: PMC6934883, DOI: 10.1093/ofid/ofz528.Peer-Reviewed Original ResearchAntiretroviral therapyHIV RNACerebrospinal fluidBlood-brain barrier integrityCentral nervous system pathologyCNS immune activationCSF HIV RNANervous system pathologyCSF HIVCSF RNAImmune activationCNS injuryCopies/Neuropsychological testingSystem pathologyBarrier integrityCNS parametersHIVStandard assayExecutive functionRNAInjuryTherapySignificance of RNAPathology
2018
Single-cell RNA sequencing reveals microglia-like cells in cerebrospinal fluid during virologically suppressed HIV
Farhadian SF, Mehta SS, Zografou C, Robertson K, Price RW, Pappalardo J, Chiarella J, Hafler DA, Spudich SS. Single-cell RNA sequencing reveals microglia-like cells in cerebrospinal fluid during virologically suppressed HIV. JCI Insight 2018, 3: e121718. PMID: 30232286, PMCID: PMC6237230, DOI: 10.1172/jci.insight.121718.Peer-Reviewed Original ResearchConceptsCerebrospinal fluidHIV infectionImmune activationAntiretroviral therapyNeuronal injuryCentral nervous system immune activationLong-term suppressive antiretroviral therapySingle-cell RNA sequencingCNS immune activationDisease-associated microgliaSuppressive antiretroviral therapyImmune cell subsetsMicroglia-like cellsGene expression signaturesNeuronal damageNeuroinflammatory diseasesRNA sequencingCell subsetsCNS cellsNeurological conditionsRare subsetNeurocognitive impairmentMyeloid cellsCellular subsetsInfection
2016
HIV Drug Resistance Mutations (DRMs) Detected by Deep Sequencing in Virologic Failure Subjects on Therapy from Hunan Province, China
Chen X, Zou X, He J, Zheng J, Chiarella J, Kozal MJ. HIV Drug Resistance Mutations (DRMs) Detected by Deep Sequencing in Virologic Failure Subjects on Therapy from Hunan Province, China. PLOS ONE 2016, 11: e0149215. PMID: 26895182, PMCID: PMC4760947, DOI: 10.1371/journal.pone.0149215.Peer-Reviewed Original ResearchConceptsDrug resistance mutationsVirologic failureDetection of DRMsPrevalence of DRMsSanger sequencingHIV drug resistance mutationsResistance mutationsART-experienced patientsART-experienced subjectsTreatment-experienced subjectsMedian viral loadNNRTI resistance mutationsStandard genotypingART adherenceViral loadAE subtypeMutation prevalenceDeep sequencingFailure subjectsExperienced subjectsResistant variantsOnly variablePatientsPrevalenceSubtypes
2015
Deep sequencing of HIV-1 variants from paired plasma and cerebrospinal fluid during primary HIV infection
Gega A, Kozal MJ, Chiarella J, Lee E, Peterson J, Hecht FM, Liegler T, St John EP, Simen BB, Price RW, Spudich SS. Deep sequencing of HIV-1 variants from paired plasma and cerebrospinal fluid during primary HIV infection. Journal Of Virus Eradication 2015, 1: 264-268. PMID: 26855971, PMCID: PMC4743659, DOI: 10.1016/s2055-6640(20)30926-2.Peer-Reviewed Original ResearchPrimary HIV infectionHIV RNA levelsCopies/mLHIV infectionCerebrospinal fluidCSF samplesAge 32 yearsDrug resistance patternsHIV-1 variantsCSF HIVHIV plasmaHigh mutational loadMutational loadDays postDeep sequencingInfectionPilot studyLow-abundance variantsResistance variantsCells/Plasma samplesViral quasispeciesLimited dataMale participantsQuasispecies
2014
Low-Frequency NNRTI-Resistant HIV-1 Variants and Relationship to Mutational Load in Antiretroviral-Naïve Subjects
Gupta S, Lataillade M, Kyriakides TC, Chiarella J, St. John EP, Webb S, Moreno EA, Simen BB, Kozal MJ. Low-Frequency NNRTI-Resistant HIV-1 Variants and Relationship to Mutational Load in Antiretroviral-Naïve Subjects. Viruses 2014, 6: 3428-3437. PMID: 25256391, PMCID: PMC4189030, DOI: 10.3390/v6093428.Peer-Reviewed Original ResearchConceptsNNRTI resistance mutationsMajor NNRTI-resistance mutationsResistance mutationsAntiretroviral-naïve subjectsARV-naïve HIVMajor NNRTI mutationsNNRTI-resistant variantsTreatment-naïve HIVHIV-1 variantsNon-nucleoside reverseMutational loadNaïve HIVNNRTI mutationsNNRTI resistanceVariant frequencyTrue burdenTherapeutic failureTreatment outcomesTreatment responseAa positionsHIVViral variantsFurther evaluationResistant variantsDeep sequencingPrevalence of WHO Transmitted Drug Resistance Mutations by Deep Sequencing in Antiretroviral-Naïve Subjects in Hunan Province, China
Xiaobai Z, Xi C, Tian H, Williams AB, Wang H, He J, Zhen J, Chiarella J, Blake LA, Turenchalk G, Kozal MJ. Prevalence of WHO Transmitted Drug Resistance Mutations by Deep Sequencing in Antiretroviral-Naïve Subjects in Hunan Province, China. PLOS ONE 2014, 9: e98740. PMID: 24896087, PMCID: PMC4045886, DOI: 10.1371/journal.pone.0098740.Peer-Reviewed Original ResearchConceptsART-naïve subjectsFirst-line antiretroviral therapyLine Antiretroviral TherapyPI TDRsDrug resistance mutationsNNRTI TDRAntiretroviral therapyPI mutationsPI/r useTransmitted Drug Resistance MutationsResistance mutationsAntiretroviral-naïve subjectsAdvanced chronic diseaseHigh-level resistanceAdvanced diseaseNNRTI mutationsNevirapine resistanceNRTI resistanceHIV variantsTime of testingChronic diseasesAE subtypeTreatment responseSubtype AER useO64 EFFECT OF BASELINE NS5A POLYMORPHISMS ON VIROLOGIC RESPONSE TO THE ALL-ORAL COMBINATION OF DACLATASVIR + SOFOSBUVIR ± RIBAVIRIN IN PATIENTS WITH CHRONIC HCV INFECTION
McPhee F, Zhou N, Yang X, Hernandez D, Chiarella J, Kozal M. O64 EFFECT OF BASELINE NS5A POLYMORPHISMS ON VIROLOGIC RESPONSE TO THE ALL-ORAL COMBINATION OF DACLATASVIR + SOFOSBUVIR ± RIBAVIRIN IN PATIENTS WITH CHRONIC HCV INFECTION. Journal Of Hepatology 2014, 60: s26-s27. DOI: 10.1016/s0168-8278(14)60066-0.Peer-Reviewed Original Research