2024
HIV-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
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
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 performance
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 pathwaysDysfunctionTherapy
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
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 use
2012
Virologic Failures on Initial Boosted-PI Regimen Infrequently Possess Low-Level Variants with Major PI Resistance Mutations by Ultra-Deep Sequencing
Lataillade M, Chiarella J, Yang R, DeGrosky M, Uy J, Seekins D, Simen B, St. John E, Moreno E, Kozal M. Virologic Failures on Initial Boosted-PI Regimen Infrequently Possess Low-Level Variants with Major PI Resistance Mutations by Ultra-Deep Sequencing. PLOS ONE 2012, 7: e30118. PMID: 22355307, PMCID: PMC3280244, DOI: 10.1371/journal.pone.0030118.Peer-Reviewed Original ResearchConceptsPI/rDrug-resistant mutationsVirologic failureUltra-deep sequencingR regimenLow-level resistant variantsMajor PI resistance mutationsPI/r regimenResistant variantsARV-naïve subjectsPI-resistant variantsHIV-positive patientsAtazanavir/ritonavirLopinavir/ritonavirM184V/ILow-level variantsPI resistance mutationsMinority of casesTenofovir/RegimenStanford HIVdbResistance mutationsPhenotypic resistanceResistant mutationsStandard genotyping
2011
Prevalence of Low-Level HIV-1 Variants with Reverse Transcriptase Mutation K65R and the Effect of Antiretroviral Drug Exposure on Variant Levels
Kozal MJ, Chiarella J, St John EP, Moreno EA, Simen BB, Arnold TE, Lataillade M. Prevalence of Low-Level HIV-1 Variants with Reverse Transcriptase Mutation K65R and the Effect of Antiretroviral Drug Exposure on Variant Levels. Antiviral Therapy 2011, 16: 925-929. PMID: 21900725, DOI: 10.3851/imp1851.Peer-Reviewed Original ResearchConceptsTreatment-naive individualsDifferent HIV-1 subtypesARV-naive subjectsHIV-1 subtypesAntiretroviral exposureViral loadSubtype CUltra-deep sequencingReverse Transcriptase Mutation K65RRitonavir-boosted protease inhibitorHIV-1 subtype CResistant variantsAntiretroviral drug exposurePlasma viral loadTreatment-naive subjectsLow-level variantsPre-therapy levelsHIV-1 variantsDrug resistance mutationsMutation K65RVirological failureSubtype BDrug exposureMutational loadHigh mutation load
2010
Prevalence and Clinical Significance of HIV Drug Resistance Mutations by Ultra-Deep Sequencing in Antiretroviral-Naïve Subjects in the CASTLE Study
Lataillade M, Chiarella J, Yang R, Schnittman S, Wirtz V, Uy J, Seekins D, Krystal M, Mancini M, McGrath D, Simen B, Egholm M, Kozal M. Prevalence and Clinical Significance of HIV Drug Resistance Mutations by Ultra-Deep Sequencing in Antiretroviral-Naïve Subjects in the CASTLE Study. PLOS ONE 2010, 5: e10952. PMID: 20532178, PMCID: PMC2880604, DOI: 10.1371/journal.pone.0010952.Peer-Reviewed Original ResearchConceptsARV-naïve subjectsVirologic failureUltra-deep sequencingPI TDRsTDR mutationsVirologic successWeek 48Clinical significanceHIV drug resistance mutationsAntiretroviral-naïve subjectsRate of TDRLopinavir/ritonavirM184V/IAtazanavir/ritonavirCase-control studyDrug resistance mutationsSimilar ratesNNRTI TDRCD4 countVirologic responseViral loadControl studyBaseline samplesResistance mutationsBaseline rate
2009
Low-Abundance HIV Drug-Resistant Viral Variants in Treatment-Experienced Persons Correlate with Historical Antiretroviral Use
Le T, Chiarella J, Simen BB, Hanczaruk B, Egholm M, Landry ML, Dieckhaus K, Rosen MI, Kozal MJ. Low-Abundance HIV Drug-Resistant Viral Variants in Treatment-Experienced Persons Correlate with Historical Antiretroviral Use. PLOS ONE 2009, 4: e6079. PMID: 19562031, PMCID: PMC2698118, DOI: 10.1371/journal.pone.0006079.Peer-Reviewed Original ResearchConceptsAntiretroviral treatment historyDrug-resistant mutationsVirologic failureAntiretroviral useDrug-resistant variantsTreatment historyOverall burdenGenotypic resistanceHIV drug-resistant mutationsHIV drug-resistant variantsStanford HIV database algorithmDrug-resistant viral variantsSubsequent antiretroviral regimensTreatment-experienced patientsConventional genotypingPrior treatment historyUltra-deep pyrosequencingSanger sequencingAntiretroviral regimensMore antiretroviralsChart reviewAntiretroviral drugsUltra-deep sequencingClinical implicationsViral variants
2007
Natural Polymorphism of the HIV-1 Integrase Gene and Mutations associated with Integrase Inhibitor Resistance
Lataillade M, Chiarella J, Kozal MJ. Natural Polymorphism of the HIV-1 Integrase Gene and Mutations associated with Integrase Inhibitor Resistance. Antiviral Therapy 2007, 12: 563-570. PMID: 17668566, DOI: 10.1177/135965350701200411.Peer-Reviewed Original ResearchConceptsHIV-1 clade BHIV-1 integrase geneINI-naive patientsStrand transfer inhibitorsHIV-1 integrationGene polymorphismsINI resistanceExcellent virological responseClinical HIV-1Late-stage clinical developmentLos Alamos databaseIntegrase inhibitor resistanceNatural polymorphismsHigh-level resistanceI203MVirological responseClade BClinical trialsHIV-1Aa positionsE138KLate-stage developmentClinical developmentA128TDrug resistance
2006
A population-based and longitudinal study of sexual behavior and multidrug-resistant HIV among patients in clinical care.
Kozal MJ, Amico KR, Chiarella J, Cornman D, Fisher W, Fisher J, Friedland G. A population-based and longitudinal study of sexual behavior and multidrug-resistant HIV among patients in clinical care. Medscape Journal Of Medicine 2006, 8: 72. PMID: 16926811, PMCID: PMC1785162.Peer-Reviewed Original ResearchConceptsSexual risk behaviorsUnprotected sexual eventsRisk behaviorsSelf-reported sexual risk behaviorDrug resistanceSerial cross-sectional analysisClasses of ARVsMultidrug-resistant HIVHIV-positive patientsAntiretroviral drug classesGenotypic drug resistanceHIV viral loadHIV sexual risk behaviorsHIV drug resistanceDrug-resistant HIVUnprotected sexual behaviorSame time pointsSexual eventsCross-sectional analysisGreat public healthVirologic resultsResistant HIVViral loadActive patientsARV resistance
2005
HIV Drug Resistance and HIV Transmission Risk Behaviors Among Active Injection Drug Users
Kozal MJ, Amico KR, Chiarella J, Cornman D, Fisher W, Fisher J, Friedland G. HIV Drug Resistance and HIV Transmission Risk Behaviors Among Active Injection Drug Users. JAIDS Journal Of Acquired Immune Deficiency Syndromes 2005, 40: 106-109. PMID: 16123691, DOI: 10.1097/01.qai.0000159666.95455.d2.Peer-Reviewed Original ResearchConceptsInjection drug usersDrug-resistant HIVHIV drug resistanceResistant HIVDrug usersRisk behaviorsClinical careActive injection drug usersDrug resistanceHIV transmission risk behaviorsTransmission risk behaviorsInjection risk behaviorsRetrospective studyInjection drugsHIVPrevious monthCareSubstantial numberMultiple partnersDrugsSmall proportionPatientsProportionNeedleMonths