2024
Prevalence 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 impairmentHIV
2023
Cerebrospinal 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 ageBrain volumetrics differ by Fiebig stage in acute HIV infection
Bolzenius J, Sacdalan C, Ndhlovu L, Sailasuta N, Trautmann L, Tipsuk S, Crowell T, Suttichom D, Colby D, Phanuphak N, Chan P, Premeaux T, Kroon E, Vasan S, Hsu D, Valcour V, Ananworanich J, Robb M, Ake J, Pohl K, Sriplienchan S, Spudich S, Paul R. Brain volumetrics differ by Fiebig stage in acute HIV infection. AIDS 2023, 37: 861-869. PMID: 36723491, PMCID: PMC10079583, DOI: 10.1097/qad.0000000000003496.Peer-Reviewed Original ResearchConceptsAcute HIV infectionNucleus accumbensFiebig stagesAcute infectionHIV infectionCaudate nucleusBrain volumeLower regional brain volumesAntiretroviral therapy initiationMarkers of neuroinflammationBrain volume alterationsCross-sectional studyRegional brain volumesT1-weighted scansTherapy initiationChronic infectionBrain volumetricsBrain disruptionThai malesViral factorsPutamenVolume alterationsAccumbensInfectionStimulant use
2022
Correlation between CD4/CD8 ratio and neurocognitive performance during early HIV infection
Le LT, Price RW, Gisslén M, Zetterberg H, Emu B, Fabre R, Christian P, Andersen S, Spudich S, Vassallo M. Correlation between CD4/CD8 ratio and neurocognitive performance during early HIV infection. HIV Medicine 2022, 24: 442-452. PMID: 36134890, DOI: 10.1111/hiv.13411.Peer-Reviewed Original ResearchConceptsCD4/CD8 ratioPrimary HIV infectionCD8 ratioImmune activationHIV infectionNeuronal injuryAntiretroviral treatmentNeurocognitive performanceMean CD4/CD8 ratioCSF neurofilament light chainART-naïve participantsEarly HIV infectionCerebrospinal fluid markersNeurofilament light chainNeuropsychological testing performancePsychomotor speed performancePHI participantsStudy cohortCSF markersChronic infectionBrain injuryRetrospective analysisFluid markersInfectionInjuryLong-term antiretroviral therapy initiated in acute HIV infection prevents residual dysfunction of HIV-specific CD8+ T cells
Takata H, Kakazu J, Mitchell J, Kroon E, Colby D, Sacdalan C, Bai H, Ehrenberg P, Geretz A, Buranapraditkun S, Pinyakorn S, Intasan J, Tipsuk S, Suttichom D, Prueksakaew P, Chalermchai T, Chomchey N, Phanuphak N, de Souza M, Michael N, Robb M, Haddad E, Crowell T, Vasan S, Valcour V, Douek D, Thomas R, Rolland M, Chomont N, Ananworanich J, Trautmann L, Teeratakulpisarn N, Pattanachaiwit S, Sriplienchan S, Tantivitayakul P, Kanaprach R, Ruxrungtham K, Dumrongpisutikul N, Rojnuckarin P, Chottanapund S, Poltavee K, Luekasemsuk T, Savadsuk H, Puttamsawin S, Benjapornpong K, Ratnaratorn N, Tangnaree K, Munkong C, Thaimanee R, Eamyoung P, Ubolyam S, Lerdlum S, Manasnayakorn S, Rerknimitr R, Sirivichayakul S, Wattanaboonyongcharoen P, Cowden J, Schuetz A, Akapirat S, Churikanont N, Getchalarat S, Hsu D, Turk E, Butterworth O, Milazzo M, Eller L, Ake J, Eller L, Spudich S, Fox L, Ratto-Kim S, DeGruttola V, Chinvarun Y, Sithinamsuwan P, Fletcher J, Shiramizu B, Schuetz A. Long-term antiretroviral therapy initiated in acute HIV infection prevents residual dysfunction of HIV-specific CD8+ T cells. EBioMedicine 2022, 84: 104253. PMID: 36088683, PMCID: PMC9471490, DOI: 10.1016/j.ebiom.2022.104253.Peer-Reviewed Original ResearchConceptsHIV-specific CD8Long-term antiretroviral therapyFunctional HIV-specific CD8Acute HIV infectionAntiretroviral therapyT cellsART initiationHIV infectionResidual dysfunctionVitro recallTCF-1 expressionChronic HIV infectionHIV remission strategiesT cell numbersT cell responsesInfection ex vivoStem cell-like propertiesCell numberCell-like propertiesART interruptionSpontaneous controllersViral reboundAcute infectionHIV remissionRemission strategiesNeuropathogenesis of HIV-1: insights from across the spectrum of acute through long-term treated infection
Killingsworth L, Spudich S. Neuropathogenesis of HIV-1: insights from across the spectrum of acute through long-term treated infection. Seminars In Immunopathology 2022, 44: 709-724. PMID: 35882661, PMCID: PMC10126949, DOI: 10.1007/s00281-022-00953-5.Peer-Reviewed Original ResearchConceptsCentral nervous systemHIV infectionInflammatory responseHIV entryChronic HIV infectionAcute HIV infectionNeuropathogenesis of HIVEarly inflammatory responsePathological inflammatory responsesOngoing neuropathologyAntiretroviral therapyViral suppressionNeurologic healthViral reservoirChronic infectionImmune mechanismsT lymphocytesHIV-1Viral infectionNervous systemInfectionHIVPathological consequencesBrainNeuropathogenesisHIV 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 activationIndividual Differences in CD4/CD8 T-Cell Ratio Trajectories and Associated Risk Profiles Modeled From Acute HIV Infection
Paul R, Cho K, Bolzenius J, Sacdalan C, Ndhlovu LC, Trautmann L, Krebs S, Tipsuk S, Crowell TA, Suttichom D, Colby DJ, Premeaux TA, Phanuphak N, Chan P, Kroon E, Vasan S, Hsu D, Carrico A, Valcour V, Ananworanich J, Robb ML, Ake JA, Sriplienchan S, Spudich S, Team F. Individual Differences in CD4/CD8 T-Cell Ratio Trajectories and Associated Risk Profiles Modeled From Acute HIV Infection. Psychosomatic Medicine 2022, 84: 976-983. PMID: 36162059, PMCID: PMC9553252, DOI: 10.1097/psy.0000000000001129.Peer-Reviewed Original ResearchConceptsAcute HIV infectionCD4/CD8 T-cell ratioCD8 T-cell ratioAntiretroviral therapyT-cell countsT-cell recoveryT cell ratioHigh viral loadViral loadHigh CD8Slower CD4HIV infectionLower white blood cell countWeeks of ARTRisk profileWhite blood cell countT-cell trajectoriesMedian viral loadStandard antiretroviral therapyBlood cell countLower eosinophil countsWorse mental healthAHI participantsART onsetFiebig IImmunological, Cognitive, and Psychiatric Outcomes After Initiating Efavirenz- and Dolutegravir-based Antiretroviral Therapy During Acute Human Immunodeficiency Virus Infection
Chan P, Yoon B, Colby D, Kroon E, Sacdalan C, Sriplienchan S, Pinyakorn S, Ananworanich J, Valcour V, Vasan S, Hsu D, Phanuphak N, Paul R, Spudich S. Immunological, Cognitive, and Psychiatric Outcomes After Initiating Efavirenz- and Dolutegravir-based Antiretroviral Therapy During Acute Human Immunodeficiency Virus Infection. Clinical Infectious Diseases 2022, 76: e718-e726. PMID: 35687498, PMCID: PMC9907536, DOI: 10.1093/cid/ciac466.Peer-Reviewed Original ResearchConceptsAcute HIV-1 infectionT-cell countsDTG-based antiretroviral therapyAntiretroviral therapyDTG groupEFV groupWeek 96Week 24CD4/CD8 ratioNucleoside reverse transcriptase inhibitorHuman immunodeficiency virus type 1Immunodeficiency virus type 1Fiebig stages IPlasma viral suppressionAcute HIV infectionTreatment-naive individualsHIV-1 infectionPatient Health QuestionnaireReverse transcriptase inhibitorVirus type 1Greater incrementART regimensCD8 ratioViral suppressionHIV infectionHIV Disease Dynamics and Markers of Inflammation and CNS Injury During Primary HIV Infection and Their Relationship to Cognitive Performance
Longino AA, Paul R, Wang Y, Lama JR, Brandes P, Ruiz E, Correa C, Keating S, Spudich SS, Pilcher C, Vecchio A, Pasalar S, Ignacio R, Valdez R, Dasgupta S, Robertson K, Duerr A. HIV Disease Dynamics and Markers of Inflammation and CNS Injury During Primary HIV Infection and Their Relationship to Cognitive Performance. JAIDS Journal Of Acquired Immune Deficiency Syndromes 2022, 89: 183-190. PMID: 34629415, PMCID: PMC8752485, DOI: 10.1097/qai.0000000000002832.Peer-Reviewed Original ResearchConceptsAcute HIV infectionAntiretroviral therapyHIV infectionWeek 192CNS injuryCSF biomarkersNP scoresHigher pre-ART VLCognitive performanceChronic cognitive symptomsSustained antiretroviral therapyPrimary HIV infectionMarkers of inflammationCerebrospinal fluid biomarkersPsychosocial risk factorsART initiationCNS inflammationNeuronal injuryAcute infectionImmune activationFluid biomarkersRisk factorsHIV disease dynamicsInjury peaksCognitive symptoms
2021
Abrupt and altered cell-type specific DNA methylation profiles in blood during acute HIV infection persists despite prompt initiation of ART
Corley MJ, Sacdalan C, Pang APS, Chomchey N, Ratnaratorn N, Valcour V, Kroon E, Cho KS, Belden AC, Colby D, Robb M, Hsu D, Spudich S, Paul R, Vasan S, Ndhlovu LC, . Abrupt and altered cell-type specific DNA methylation profiles in blood during acute HIV infection persists despite prompt initiation of ART. PLOS Pathogens 2021, 17: e1009785. PMID: 34388205, PMCID: PMC8386872, DOI: 10.1371/journal.ppat.1009785.Peer-Reviewed Original ResearchConceptsAntiretroviral therapyT lymphocytesCD4/CD8 ratioHIV infection cohortHost epigenetic landscapeAcute HIV infectionSpecific DNA methylation profileInfection cohortInfection HIVCD4 countCD8 ratioHIV infectionPrompt initiationViral loadHIV medicineViral persistenceEarly initiationT cellsHIV-1Disease pathogenesisClinical phenotypeMonocytesCD4HIVLymphocytesCognitive trajectories after treatment in acute HIV infection
Chan P, Kerr SJ, Kroon E, Colby D, Sacdalan C, Hellmuth J, Reiss P, Vasan S, Ananworanich J, Valcour V, Spudich S, Paul R. Cognitive trajectories after treatment in acute HIV infection. AIDS 2021, 35: 883-888. PMID: 33534200, DOI: 10.1097/qad.0000000000002831.Peer-Reviewed Original ResearchConceptsAcute HIV-1 infectionAntiretroviral therapyWeek 288Week 96Cognitive performanceAcute HIV infectionSuppressive antiretroviral therapyHIV-1 infectionTrajectory subgroupsWorse depressive symptomsWorse baseline cognitive performanceImpaired cognitive performanceFine motor speedAHI diagnosisViral suppressionHIV infectionWeek 12Baseline cognitive performanceLower baseline performanceHIV-1Depressive symptomsCognitive symptomsPosthoc analysisPsychomotor speedCognitive outcomesChapter 43 HIV and Other Retroviral Infections of the Nervous System
Peluso M, Spudich S. Chapter 43 HIV and Other Retroviral Infections of the Nervous System. 2021, 765-784. DOI: 10.1016/b978-0-12-819306-8.00043-5.Peer-Reviewed Original ResearchAntiretroviral therapyHIV infectionNeurologic manifestationsHuman immunodeficiency virus (HIV) infectionEra of ARTSuccessful systemic treatmentImmunodeficiency virus infectionEarly HIV infectionSystemic immune systemQuality of lifeAdvanced immunosuppressionAntiretroviral statusNeurologic complicationsNeurologic presentationSystemic treatmentVirus infectionCNS effectsCognitive disordersNervous systemImmune systemInfectionRetroviral infectionComplicationsHIVTherapy
2020
Resting-state neural signatures of depressive symptoms in acute HIV
Philippi CL, Reyna L, Nedderman L, Chan P, Samboju V, Chang K, Phanuphak N, Ratnaratorn N, Hellmuth J, Benjapornpong K, Dumrongpisutikul N, Pothisri M, Robb ML, Ananworanich J, Spudich S, Valcour V, Paul R. Resting-state neural signatures of depressive symptoms in acute HIV. Journal Of NeuroVirology 2020, 26: 226-240. PMID: 31989446, PMCID: PMC7261250, DOI: 10.1007/s13365-020-00826-3.Peer-Reviewed Original ResearchConceptsResting-state functional connectivityAcute HIV infectionAnterior cingulate cortexDecreased resting-state functional connectivityDepressive symptomsAltered resting-state functional connectivityCombination antiretroviral therapyPersistent depressive symptomsUninfected control groupAmygdala seed regionPosterior cingulate/precuneusSymptoms of depressionVoxelwise regression analysesEmotion-related brain regionsAcute HIVChronic HIVThai HIVAntiretroviral therapyHIV RNASeed regionHIV infectionBlood biomarkersAHI groupLateral parietal regionsUninfected controlsLiver function test abnormalities in a longitudinal cohort of Thai individuals treated since acute HIV infection
Peluso MJ, Colby DJ, Pinyakorn S, Ubolyam S, Intasan J, Trichavaroj R, Chomchey N, Prueksakaew P, Slike BM, Krebs SJ, Jian N, Robb ML, Phanuphak P, Phanuphak N, Spudich S, Ananworanich J, Kroon E, , Teeratakulpisarn N, Pattanachaiwit S, Sacdalan C, Sriplienchan S, de Souza M, Tantivitayakul P, Poltavee K, Luekasemsuk T, Savadsuk H, Tipsuk S, Puttamsawin S, Benjapornpong K, Ratnaratorn N, Tangnaree K, Munkong C, Thaimanee R, Eamyoung P, Buranapraditkun S, Lerdlum S, Manasnayakorn S, Rerknimitr R, Sirivichayakul S, Wattanaboonyongcharoen P, Suttichom D, O'Connell R, Schuetz A, Hsu D, Akapirat S, Nuntapinit B, Tantibul N, Churikanont N, Getchalarat S, Michael N, Vasan S, Crowell T, Turk E, McCullough C, Butterworth O, Milazzo M, Anne Eller L. Liver function test abnormalities in a longitudinal cohort of Thai individuals treated since acute HIV infection. Journal Of The International AIDS Society 2020, 23: e25444. PMID: 31953919, PMCID: PMC6968973, DOI: 10.1002/jia2.25444.Peer-Reviewed Original ResearchConceptsAcute HIV infectionLiver function test abnormalitiesBaseline alanine aminotransferaseAntiretroviral therapyHIV infectionAlanine aminotransferaseALT elevationALT levelsTest abnormalitiesCopies/Baseline plasma HIV RNA levelElevated baseline alanine aminotransferasePlasma HIV RNA levelsBaseline ALT levelsBaseline HIV RNAConcomitant viral hepatitisEfavirenz-based regimensFiebig stage IIIFiebig stages IGrade 1 elevationImmediate antiretroviral therapyHIV RNA levelsEarly HIV infectionCombination of HIVThai individualsNeuropsychiatric outcomes before and after switching to dolutegravir-based therapy in an acute HIV cohort
Chan P, Goh O, Kroon E, Colby D, Sacdalan C, Pinyakorn S, Prueksakaew P, Reiss P, Ananworanich J, Valcour V, Spudich S, Paul R. Neuropsychiatric outcomes before and after switching to dolutegravir-based therapy in an acute HIV cohort. AIDS Research And Therapy 2020, 17: 1. PMID: 31907064, PMCID: PMC6945418, DOI: 10.1186/s12981-019-0257-8.Peer-Reviewed Original ResearchConceptsPatient Health Questionnaire-9Acute HIV infectionWeeks of ARTAntiretroviral therapyPHQ-9 scoresDTG-based antiretroviral therapyLower PHQ-9 scoresDolutegravir-based therapyDTG-based regimenNeuropsychiatric adverse eventsPlasma viral suppressionFirst-line treatmentPre-existing depressionLeast moderate depressionModerate-severe depressionModerate depression symptomsPercentage of participantsDTG useViral suppressionHIV cohortMedian durationAdverse eventsHIV infectionHighest quartileMultivariable analysis
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 pathwaysDysfunctionTherapySwitch to dolutegravir is well tolerated in Thais with HIV infection
Goh OQ, Colby DJ, Pinyakorn S, Sacdalan C, Kroon E, Chan P, Chomchey N, Kanaprach R, Prueksakaew P, Suttichom D, Trichavaroj R, Spudich S, Robb ML, Phanuphak P, Phanuphak N, Ananworanich J, Group O. Switch to dolutegravir is well tolerated in Thais with HIV infection. Journal Of The International AIDS Society 2019, 22: e25324. PMID: 31294931, PMCID: PMC6621926, DOI: 10.1002/jia2.25324.Peer-Reviewed Original ResearchConceptsAcute HIV infectionBody mass indexIncident hepatitis C virus infectionHepatitis C virus infectionC virus infectionAdverse eventsAntiretroviral therapyHIV infectionVirus infectionFirst-line antiretroviral therapyHepatitis C virus coinfectionLiver-related adverse eventsLower body mass indexC virus coinfectionDTG-based regimensOnly risk factorMedian body weightPossible adverse eventsHepatitis C virusAbacavir therapyLaboratory abnormalitiesMedian ageVirus coinfectionMass indexNeuropsychiatric symptomsVery Early Initiation of Antiretroviral Therapy During Acute HIV Infection Is Associated With Normalized Levels of Immune Activation Markers in Cerebrospinal Fluid but Not in Plasma
Hellmuth J, Slike BM, Sacdalan C, Best J, Kroon E, Phanuphak N, Fletcher JLK, Prueksakaew P, Jagodzinski LL, Valcour V, Robb M, Ananworanich J, Allen IE, Krebs SJ, Spudich S. Very Early Initiation of Antiretroviral Therapy During Acute HIV Infection Is Associated With Normalized Levels of Immune Activation Markers in Cerebrospinal Fluid but Not in Plasma. The Journal Of Infectious Diseases 2019, 220: 1885-1891. PMID: 30668739, PMCID: PMC6833977, DOI: 10.1093/infdis/jiz030.Peer-Reviewed Original ResearchConceptsAcute HIV infectionAntiretroviral therapyART initiationCerebrospinal fluidWeek 96Week 24HIV infectionImmune activationAHI groupHuman immunodeficiency virus (HIV) infectionEarly ART initiationPlasma CCL2 levelsTrajectory of HIVChronic immune activationImmune activation markersSuppressive antiretroviral therapyImmunodeficiency virus infectionInterleukin-6 levelsMarkers of inflammationPlasma neopterin levelsWeeks of treatmentCentral nervous systemART regimenCCL2 levelsNeopterin levelsCerebrospinal Fluid Concentrations of the Synaptic Marker Neurogranin in Neuro-HIV and Other Neurological Disorders
Yilmaz A, Fuchs D, Price RW, Spudich S, Blennow K, Zetterberg H, Gisslén M. Cerebrospinal Fluid Concentrations of the Synaptic Marker Neurogranin in Neuro-HIV and Other Neurological Disorders. Current HIV/AIDS Reports 2019, 16: 76-81. PMID: 30649659, PMCID: PMC6420419, DOI: 10.1007/s11904-019-00420-1.Peer-Reviewed Original ResearchConceptsCSF neurograninCerebrospinal fluidProinflammatory cytokines IL-1βGroup of HIVLewy body dementiaCerebrospinal fluid concentrationsCytokines IL-1βLevels of neurograninNeurogranin concentrationsNeuro-HIVHIV neuropathogenesisSynaptic injuryHIV infectionIL-1βNeurocognitive disordersFrontal cortexParkinson's diseaseUninfected controlsReviewThe aimAlzheimer's diseaseNeurological disordersFrontotemporal dementiaNeurodegenerative disordersFluid concentrationsHIV