Featured Publications
Patients with HIV-associated cancers have evidence of increased T cell dysfunction and exhaustion prior to cancer diagnosis
Chaudhary O, Trotta D, Wang K, Wang X, Chu X, Bradley C, Okulicz J, Maves RC, Kronmann K, Schofield CM, Blaylock JM, Deng Y, Schalper KA, Kaech SM, Agan B, Ganesan A, Emu B. Patients with HIV-associated cancers have evidence of increased T cell dysfunction and exhaustion prior to cancer diagnosis. Journal For ImmunoTherapy Of Cancer 2022, 10: e004564. PMID: 35470232, PMCID: PMC9039380, DOI: 10.1136/jitc-2022-004564.Peer-Reviewed Original ResearchMeSH KeywordsBiomarkersCase-Control StudiesHIV InfectionsHIV-1HumansNeoplasmsProgrammed Cell Death 1 ReceptorConceptsViral suppressionTraditional risk factorsCase-control study designMarker of riskControl study designHIV infectionStudy cohortInhibitory receptorsRisk factorsCancer casesT cellsStudy designCancer diagnosisPLWHHIVCancerRiskCD4CellsPatientsTranscription factorsClinical cancer diagnosisCohortSuppressionInfectionDecreased Overall Survival in HIV-associated Non–small-cell Lung Cancer
Hysell K, Yusuf R, Barakat L, Virata M, Gan G, Deng Y, Perez-Irizarry J, Vega T, Goldberg SB, Emu B. Decreased Overall Survival in HIV-associated Non–small-cell Lung Cancer. Clinical Lung Cancer 2020, 22: e498-e505. PMID: 33468393, PMCID: PMC8169710, DOI: 10.1016/j.cllc.2020.11.006.Peer-Reviewed Original ResearchConceptsCell lung cancerGeneral patientsNSCLC populationLung cancerCox proportional hazards modelYale-New Haven HospitalGeneral NSCLC populationOutcomes of patientsOverall median survivalRetrospective cohort studyPredictors of survivalKaplan-Meier curvesHIV-1 RNACopies/mLLog-rank testProportional hazards modelNew Haven HospitalCancer treatment regimensMedian CD4Antiretroviral therapyCohort studyMedian survivalOverall survivalHIV infectionMedian age
2023
Safety and Activity of Immune Checkpoint Inhibitors in People Living With HIV and Cancer: A Real-World Report From the Cancer Therapy Using Checkpoint Inhibitors in People Living With HIV-International (CATCH-IT) Consortium
El Zarif T, Nassar A, Adib E, Fitzgerald B, Huang J, Mouhieddine T, Rubinstein P, Nonato T, McKay R, Li M, Mittra A, Owen D, Baiocchi R, Lorentsen M, Dittus C, Dizman N, Falohun A, Abdel-Wahab N, Diab A, Bankapur A, Reed A, Kim C, Arora A, Shah N, El-Am E, Kozaily E, Abdallah W, Al-Hader A, Abu Ghazal B, Saeed A, Drolen C, Lechner M, Drakaki A, Baena J, Nebhan C, Haykal T, Morse M, Cortellini A, Pinato D, Dalla Pria A, Hall E, Bakalov V, Bahary N, Rajkumar A, Mangla A, Shah V, Singh P, Aboubakar Nana F, Lopetegui-Lia N, Dima D, Dobbs R, Funchain P, Saleem R, Woodford R, Long G, Menzies A, Genova C, Barletta G, Puri S, Florou V, Idossa D, Saponara M, Queirolo P, Lamberti G, Addeo A, Bersanelli M, Freeman D, Xie W, Reid E, Chiao E, Sharon E, Johnson D, Ramaswami R, Bower M, Emu B, Marron T, Choueiri T, Baden L, Lurain K, Sonpavde G, Naqash A. Safety and Activity of Immune Checkpoint Inhibitors in People Living With HIV and Cancer: A Real-World Report From the Cancer Therapy Using Checkpoint Inhibitors in People Living With HIV-International (CATCH-IT) Consortium. Journal Of Clinical Oncology 2023, 41: 3712-3723. PMID: 37192435, PMCID: PMC10351941, DOI: 10.1200/jco.22.02459.Peer-Reviewed Original ResearchConceptsImmune-related adverse eventsProgression-free survivalObjective response rateOverall survivalMetastatic NSCLCCheckpoint inhibitorsGrade immune-related adverse eventsImmune checkpoint inhibitor trialsNeck squamous cell carcinomaActivity of ICICheckpoint inhibitor trialsCohort of PWHImmune checkpoint inhibitorsHIV viral loadKaplan-Meier methodSquamous cell carcinomaUse of ICIMean survival timeMost common cancersL1 monotherapyRECIST 1.1Adverse eventsInhibitor trialsMedian ageAdvanced cancer
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
Phase 3 Study of Ibalizumab for Multidrug-Resistant HIV-1
Emu B, Fessel J, Schrader S, Kumar P, Richmond G, Win S, Weinheimer S, Marsolais C, Lewis S. Phase 3 Study of Ibalizumab for Multidrug-Resistant HIV-1. New England Journal Of Medicine 2018, 379: 645-654. PMID: 30110589, DOI: 10.1056/nejmoa1711460.Peer-Reviewed Original ResearchConceptsPhase 3 studyHIV-1 infectionViral loadBackground regimenVirologic failureAdverse eventsWeek 25Multidrug-resistant HIV-1 infectionMDR HIV-1 infectionMean baseline viral loadMultidrug-resistant HIV-1Human immunodeficiency virus type 1Immunodeficiency virus type 1Control periodMultiple antiretroviral therapiesViral load decreaseCommon adverse eventsMean CD4 countPrimary end pointSerious adverse eventsBaseline viral loadProportion of patientsHIV-1 RNALimited treatment optionsVirus type 1HIV and Age Do Not Synergistically Affect Age-Related T-Cell Markers
Farhadian S, Jalbert E, Deng Y, Goetz MB, Park LS, Justice A, Dubrow R, Emu B. HIV and Age Do Not Synergistically Affect Age-Related T-Cell Markers. JAIDS Journal Of Acquired Immune Deficiency Syndromes 2018, 77: 337-344. PMID: 29140874, PMCID: PMC5807137, DOI: 10.1097/qai.0000000000001595.Peer-Reviewed Original ResearchConceptsCD8 T cellsT-cell markersCD4 T cellsHIV infectionT cellsAntiretroviral therapyEffector memory CD4 T cellsImmune systemVeterans Aging Cohort StudyMemory CD4 T cellsNaive CD4 T cellsAging Cohort StudyT cell subsetsT-cell phenotypeCopies/mLCross-sectional studyRace/ethnicityChronic HIVUninfected subjectsUninfected menCohort studyHIV diseaseHigher proportionHIV serostatusHIV status
2017
Clinically significant mutations in HIV-infected patients with lung adenocarcinoma
Thaler J, Sigel C, Beasley MB, Wisnivesky J, Crothers K, Bauml J, Hysell K, Emu B, Borsu L, Sigel K. Clinically significant mutations in HIV-infected patients with lung adenocarcinoma. British Journal Of Cancer 2017, 117: 1392-1395. PMID: 28934759, PMCID: PMC5672933, DOI: 10.1038/bjc.2017.333.Peer-Reviewed Original ResearchConceptsPrevalence of eGFRHIV statusKRAS mutationsLung adenocarcinomaMutation statusLung adenocarcinoma patientsPresence of KRASUninfected comparatorsOverall survivalAdenocarcinoma patientsTumor EGFRLung cancerMutational testingPatientsMajor causeEGFRPrevalenceGenetic alterationsHIVAdenocarcinomaSignificant mutationsStatusSurvivalMutationsSubjects
2014
Composition and Function of T Cell Subpopulations Are Slow to Change Despite Effective Antiretroviral Treatment of HIV Disease
Emu B, Moretto WJ, Hoh R, Krone M, Martin JN, Nixon DF, Deeks SG, McCune JM. Composition and Function of T Cell Subpopulations Are Slow to Change Despite Effective Antiretroviral Treatment of HIV Disease. PLOS ONE 2014, 9: e85613. PMID: 24465619, PMCID: PMC3897457, DOI: 10.1371/journal.pone.0085613.Peer-Reviewed Original ResearchConceptsT cell subpopulationsT cellsCell subpopulationsViral loadCMV-specific T-cell responsesNaïve T cell numbersLong-term viral suppressionIncrease of CD4Effective antiretroviral treatmentT cell frequenciesUndetectable viral loadT cell numbersT-cell depletionT cell responsesT-cell phenotypeNormal immune systemT cell populationsLow Ki67 expressionT cell functionIndependent homeostatic regulationDifferent proliferative responsesAntiretroviral therapyViral suppressionHIV diseaseAntiretroviral treatment
2011
A Low T Regulatory Cell Response May Contribute to Both Viral Control and Generalized Immune Activation in HIV Controllers
Hunt PW, Landay AL, Sinclair E, Martinson JA, Hatano H, Emu B, Norris PJ, Busch MP, Martin JN, Brooks C, McCune JM, Deeks SG. A Low T Regulatory Cell Response May Contribute to Both Viral Control and Generalized Immune Activation in HIV Controllers. PLOS ONE 2011, 6: e15924. PMID: 21305005, PMCID: PMC3031543, DOI: 10.1371/journal.pone.0015924.Peer-Reviewed Original ResearchConceptsT cell activation levelsT cell responsesHigh T-cell activation levelsHIV-specific T-cell responsesRegulatory cell responsesHIV controllersImmune activationCell responsesCMV-specific T cellsT regulatory (Treg) cell responsesTreatment-mediated viral suppressionEffective adaptive immune responseCMV-specific CD4Generalized immune activationHIV-specific CD4Lower Treg frequenciesNon-AIDS morbiditiesT cell frequenciesT cell lossT-cell depletionT cell dysfunctionAbsence of therapyActivation levelsAdaptive immune responsesDevelopment of vaccinesHIV disease progression correlates with the generation of dysfunctional naive CD8low T cells
Favre D, Stoddart CA, Emu B, Hoh R, Martin JN, Hecht FM, Deeks SG, McCune JM. HIV disease progression correlates with the generation of dysfunctional naive CD8low T cells. Blood 2011, 117: 2189-2199. PMID: 21200021, PMCID: PMC3062328, DOI: 10.1182/blood-2010-06-288035.Peer-Reviewed Original ResearchMeSH KeywordsAdultAnimalsCalcium SignalingCD8-Positive T-LymphocytesDisease ProgressionHIV InfectionsHumansIn Vitro TechniquesInterferon alpha-2Interferon-alphaInterleukin-2Major Histocompatibility ComplexMART-1 AntigenMiceMice, SCIDMice, TransgenicMiddle AgedP38 Mitogen-Activated Protein KinasesPhosphorylationReceptors, Antigen, T-CellRecombinant ProteinsSignal TransductionThymus GlandUp-RegulationViral LoadConceptsPeripheral blood mononuclear cellsT cellsHIV diseaseHIV infectionSCID-hu Thy/Liv mouse modelMajor histocompatibility complex class ICD8low T cellsProgressive HIV diseaseHIV disease progressionHistocompatibility complex class IBlood mononuclear cellsInterferon-α treatmentAntigen-presenting cellsComplex class IT cell receptor complexCD8β chainNaive compartmentΑ treatmentMononuclear cellsDisease progressionMouse modelStromal cellsLow expressionClass IMHC
2008
HLA Class I-Restricted T-Cell Responses May Contribute to the Control of Human Immunodeficiency Virus Infection, but Such Responses Are Not Always Necessary for Long-Term Virus Control
Emu B, Sinclair E, Hatano H, Ferre A, Shacklett B, Martin JN, McCune JM, Deeks SG. HLA Class I-Restricted T-Cell Responses May Contribute to the Control of Human Immunodeficiency Virus Infection, but Such Responses Are Not Always Necessary for Long-Term Virus Control. Journal Of Virology 2008, 82: 5398-5407. PMID: 18353945, PMCID: PMC2395228, DOI: 10.1128/jvi.02176-07.Peer-Reviewed Original ResearchConceptsT cell responsesHLA class IElite controllersT cellsViremic controllersVirus controlClass IInterleukin-2HIV-specific T-cell responsesT cell-mediated controlUndetectable HIV RNA levelsHuman immunodeficiency virus (HIV) infectionHLA class I allelesProtective class IHIV RNA levelsHLA class I polymorphismImmunodeficiency virus infectionLong-term virus controlCell-mediated controlHuman immunodeficiency virusClass I allelesClass I polymorphismAntiretroviral therapyHIV controllersHIV transmissionRelationship between T Cell Activation and CD4+ T Cell Count in HIV-Seropositive Individuals with Undetectable Plasma HIV RNA Levels in the Absence of Therapy
Hunt PW, Brenchley J, Sinclair E, McCune JM, Roland M, Shafer K, Hsue P, Emu B, Krone M, Lampiris H, Douek D, Martin JN, Deeks SG. Relationship between T Cell Activation and CD4+ T Cell Count in HIV-Seropositive Individuals with Undetectable Plasma HIV RNA Levels in the Absence of Therapy. The Journal Of Infectious Diseases 2008, 197: 126-133. PMID: 18171295, PMCID: PMC3466592, DOI: 10.1086/524143.Peer-Reviewed Original ResearchConceptsUndetectable plasma HIV RNA levelsT cell activationPlasma HIV RNA levelsHIV RNA levelsHIV-negative subjectsHigh LPS levelsCell activationCell countAntiretroviral therapyLPS levelsHigh T-cell activation levelsHIV-specific immune responsesT cell activation levelsUntreated human immunodeficiency virusPlasma lipopolysaccharide levelsRNA levelsHIV-seropositive individualsT-cell countsT cell lossHuman immunodeficiency virusAbsence of therapyActivation levelsCells/Measurable viremiaMucosal translocation
2007
Loss of T cell responses following long-term cryopreservation
Owen RE, Sinclair E, Emu B, Heitman JW, Hirschkorn DF, Epling CL, Tan QX, Custer B, Harris JM, Jacobson MA, McCune JM, Martin JN, Hecht FM, Deeks SG, Norris PJ. Loss of T cell responses following long-term cryopreservation. Journal Of Immunological Methods 2007, 326: 93-115. PMID: 17707394, PMCID: PMC2065759, DOI: 10.1016/j.jim.2007.07.012.Peer-Reviewed Original ResearchConceptsT cell IFN-gamma responsesT cell responsesHuman immunodeficiency virusIFN-gamma responsesPeripheral blood mononuclear cellsCell responsesLong-term cryopreservationPeptide poolsHIV-negative individualsBlood mononuclear cellsLoss of responseT cell apoptosisPhenotypic marker expressionDecrement of responseOvernight restingEffector cellsImmunodeficiency virusExogenous antigensMononuclear cellsShort-term cryopreservationHIV peptidesFuture vaccinesImpact of cryopreservationPathogenesis studiesMarker expression
2005
Phenotypic, Functional, and Kinetic Parameters Associated with Apparent T-Cell Control of Human Immunodeficiency Virus Replication in Individuals with and without Antiretroviral Treatment
Emu B, Sinclair E, Favre D, Moretto WJ, Hsue P, Hoh R, Martin JN, Nixon DF, McCune JM, Deeks SG. Phenotypic, Functional, and Kinetic Parameters Associated with Apparent T-Cell Control of Human Immunodeficiency Virus Replication in Individuals with and without Antiretroviral Treatment. Journal Of Virology 2005, 79: 14169-14178. PMID: 16254352, PMCID: PMC1280210, DOI: 10.1128/jvi.79.22.14169-14178.2005.Peer-Reviewed Original ResearchConceptsHIV-specific T cellsT cellsT cell activationHIV diseaseImmune activationHuman immunodeficiency virus (HIV) replicationAdvanced HIV diseaseDrug-resistant viremiaGeneralized immune activationHIV-specific ILMultidrug-resistant HIVQuiescent immune systemActive antiretroviral therapyCytokine flow cytometryT cell controlHigh-level viremiaLow-level viremiaPresence of HIVT cell subsetsHuman immunodeficiency virusImmunodeficiency virus replicationT cell subpopulationsAbsence of therapyPresence of therapyAntiretroviral therapy