2022
Single-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 candidates
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
2014
Prevalence 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
2004
Antiretroviral resistance and high-risk transmission behavior among HIV-positive patients in clinical care
Kozal MJ, Amico KR, Chiarella J, Schreibman T, Cornman D, Fisher W, Fisher J, Friedland G. Antiretroviral resistance and high-risk transmission behavior among HIV-positive patients in clinical care. AIDS 2004, 18: 2185-2189. PMID: 15577652, DOI: 10.1097/00002030-200411050-00011.Peer-Reviewed Original ResearchConceptsHIV-positive patientsTransmission risk behaviorsHIV transmission risk behaviorsViral loadUnprotected sexual eventsRisk behaviorsAntiretroviral therapyCopies/Clinical careHIV sexual transmission risk behaviorsUnprotected sexHigh-risk transmission behaviorsSexual transmission risk behaviorLower mental health scoresHIV transmission eventsUndetectable viral loadProportion of patientsHIV drug resistanceDrug-resistant HIVMental health scoresCross-sectional studyHIV transmission behaviorsDrug resistance dataAntiretroviral resistanceResistant HIV