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
Antiretroviral Therapy Intensification for Neurocognitive Impairment in Human Immunodeficiency Virus
Letendre S, Chen H, McKhann A, Roa J, Vecchio A, Daar E, Berzins B, Hunt P, Marra C, Campbell T, Coombs R, Ma Q, Swaminathan S, Macatangay B, Morse G, Miller T, Rusin D, Greninger A, Ha B, Alston-Smith B, Robertson K, Paul R, Spudich S, Team T. Antiretroviral Therapy Intensification for Neurocognitive Impairment in Human Immunodeficiency Virus. Clinical Infectious Diseases 2023, 77: 866-874. PMID: 37183889, PMCID: PMC10506779, DOI: 10.1093/cid/ciad265.Peer-Reviewed Original ResearchConceptsAntiretroviral therapyART intensificationNeurocognitive impairmentWeek 48Z-scoreAntiretroviral therapy intensificationPersistent HIV replicationPlacebo-controlled trialPlasma HIV RNASuppressive antiretroviral therapyAge 52 yearsBody mass indexHuman immunodeficiency virusCopies/mLTotal Z-scoreBaseline z-scoresCentral nervous systemDual placeboEfavirenz useTherapy intensificationHIV RNAStudy drugAdverse eventsSymptomatic HIVPrimary outcomeRebound HIV-1 in cerebrospinal fluid after antiviral therapy interruption is mainly clonally amplified R5 T cell-tropic virus
Kincer L, Joseph S, Gilleece M, Hauser B, Sizemore S, Zhou S, Di Germanio C, Zetterberg H, Fuchs D, Deeks S, Spudich S, Gisslen M, Price R, Swanstrom R. Rebound HIV-1 in cerebrospinal fluid after antiviral therapy interruption is mainly clonally amplified R5 T cell-tropic virus. Nature Microbiology 2023, 8: 260-271. PMID: 36717718, PMCID: PMC10201410, DOI: 10.1038/s41564-022-01306-6.Peer-Reviewed Original ResearchConceptsCentral nervous systemT cell-tropic virusesInfected T cellsCerebrospinal fluidAntiretroviral therapyHIV-1Rebound virusViral loadT cellsMacrophage-tropic HIV-1CSF viral loadSuppressive antiretroviral therapyHIV-1 reservoirMacrophage-tropic virusesHigh viral loadWhite blood cellsTherapy interruptionLatent reservoirLymphoid systemNervous systemSystemic infectionVirus replicationBlood cellsTransient influxVirus
2021
Cognitive 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 outcomes
2020
Selective Decay of Intact HIV-1 Proviral DNA on Antiretroviral Therapy
Gandhi R, Cyktor J, Bosch R, Mar H, Laird G, Martin A, Collier A, Riddler S, Macatangay B, Rinaldo C, Eron J, Siliciano J, McMahon D, Mellors J, Hogg E, LeBlanc R, Scello C, Palm D, Gandhi M, Fletcher C, Podany A, Aweeka F, Halvas L, Dragavon J, Joseph J, Lagattuta R, Lin L, Pederson S, Robertson K, Rubin L, Smith D, Spudich S, Tsibris A. Selective Decay of Intact HIV-1 Proviral DNA on Antiretroviral Therapy. The Journal Of Infectious Diseases 2020, 223: 225-233. PMID: 32823274, PMCID: PMC7857155, DOI: 10.1093/infdis/jiaa532.Peer-Reviewed Original ResearchConceptsTotal HIV-1 DNAResidual plasma viremiaAntiretroviral therapyHIV-1 DNAProvirus levelsPlasma viremiaLong-term antiretroviral therapyDefective HIV-1 provirusesHIV-1 proviral DNAReplication-competent reservoirSuppressive antiretroviral therapyMarkers of inflammationReplication-competent provirusesHIV-1 provirusART initiationImmune activationHIV-1Proviral DNATime pointsInfected cellsViremiaDefective provirusesInflammationTherapyProvirus
2019
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
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 levels
2018
Human Immunodeficiency Virus Type 1 RNA Detected in the Central Nervous System (CNS) After Years of Suppressive Antiretroviral Therapy Can Originate from a Replicating CNS Reservoir or Clonally Expanded Cells
Joseph SB, Kincer LP, Bowman NM, Evans C, Vinikoor MJ, Lippincott CK, Gisslén M, Spudich S, Menezes P, Robertson K, Archin N, Kashuba A, Eron JJ, Price RW, Swanstrom R. Human Immunodeficiency Virus Type 1 RNA Detected in the Central Nervous System (CNS) After Years of Suppressive Antiretroviral Therapy Can Originate from a Replicating CNS Reservoir or Clonally Expanded Cells. Clinical Infectious Diseases 2018, 69: 1345-1352. PMID: 30561541, PMCID: PMC6938202, DOI: 10.1093/cid/ciy1066.Peer-Reviewed Original ResearchConceptsCentral nervous systemHIV-1 RNA concentrationsAntiretroviral therapySuppressive antiretroviral therapyCerebrospinal fluidCNS reservoirsCSF escapeCSF HIV-1 RNA concentrationsCentral nervous system reservoirYears of ARTHuman immunodeficiency virus type 1 (HIV-1) populationHuman immunodeficiency virus type 1 (HIV-1) RNAStable antiretroviral therapyHIV-1 RNAMacrophages/microgliaInfected T cellsRNA concentrationViral envelope sequencesType 1 populationViral populationsViral suppressionMacrophage-tropicAsymptomatic participantsMultiple time pointsT cellsSingle-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 subsetsInfectionAnti-Human Immunodeficiency Virus Antibodies in the Cerebrospinal Fluid: Evidence of Early Treatment Impact on Central Nervous System Reservoir?
Burbelo PD, Price RW, Hagberg L, Hatano H, Spudich S, Deeks SG, Gisslén M. Anti-Human Immunodeficiency Virus Antibodies in the Cerebrospinal Fluid: Evidence of Early Treatment Impact on Central Nervous System Reservoir? The Journal Of Infectious Diseases 2018, 217: 1024-1032. PMID: 29401308, PMCID: PMC5939835, DOI: 10.1093/infdis/jix662.Peer-Reviewed Original ResearchConceptsCentral nervous systemHuman immunodeficiency virusAntiretroviral therapyLong-term treatmentCerebrospinal fluidHIV antibodiesCSF antibodiesEarly infectionBlood antibodyChronic infectionVirus antibodiesCentral nervous system reservoirAnti-human immunodeficiency virus antibodiesHuman immunodeficiency virus (HIV) antibodyEarly ART initiationMarkers of persistenceEffective antiretroviral therapySuppressive antiretroviral therapyPre-exposure prophylaxisART initiationHIV persistenceCNS infectionHIV reservoirImmunodeficiency virusBerlin patient
2017
Acute Retroviral Syndrome Is Associated With High Viral Burden, CD4 Depletion, and Immune Activation in Systemic and Tissue Compartments
Crowell TA, Colby DJ, Pinyakorn S, Fletcher JLK, Kroon E, Schuetz A, Krebs SJ, Slike BM, Leyre L, Chomont N, Jagodzinski LL, Sereti I, Utay NS, Dewar R, Rerknimitr R, Chomchey N, Trichavaroj R, Valcour VG, Spudich S, Michael NL, Robb ML, Phanuphak N, Ananworanich J, Teeratakulpisarn N, Sacdalan C, Sutthichom D, Rattanamanee S, Prueksakaew P, Ubolyam S, Eamyoung P, Puttamaswin S, Tipsuk S, Karnsomlap P, Ridtitid W, Connell R, Akapirat S, Phuang-Ngern Y, Sukhumvittaya S, Sajjaweerawan C, Jongrakthaitae S, Saetun P, Tragonlugsana N, Nuntapinit B, Tantibul N, Savadsuk H, Tovanabutr S. Acute Retroviral Syndrome Is Associated With High Viral Burden, CD4 Depletion, and Immune Activation in Systemic and Tissue Compartments. Clinical Infectious Diseases 2017, 66: 1540-1549. PMID: 29228130, PMCID: PMC5930255, DOI: 10.1093/cid/cix1063.Peer-Reviewed Original ResearchConceptsHigh viral burdenAcute retroviral syndromeAntiretroviral therapyCD4 depletionViral burdenImmune activationAdverse long-term clinical outcomesVoluntary human immunodeficiency virus (HIV) testingPlasma tumor necrosis factor alphaWeeks of ARTHuman immunodeficiency virus (HIV) testingLong-term clinical outcomesTumor necrosis factor alphaHigher HIV RNATotal HIV DNASuppressive antiretroviral therapyC-reactive proteinSigns/symptomsNecrosis factor alphaUnderwent lumbar punctureMultiple body compartmentsARS diagnosisFiebig stagesSigmoid biopsiesHIV RNA
2013
Cerebrospinal fluid neopterin decay characteristics after initiation of antiretroviral therapy
Yilmaz A, Yiannoutsos CT, Fuchs D, Price RW, Crozier K, Hagberg L, Spudich S, Gisslén M. Cerebrospinal fluid neopterin decay characteristics after initiation of antiretroviral therapy. Journal Of Neuroinflammation 2013, 10: 828. PMID: 23664008, PMCID: PMC3657550, DOI: 10.1186/1742-2094-10-62.Peer-Reviewed Original ResearchConceptsCSF neopterin levelsAntiretroviral therapyNeopterin levelsCerebrospinal fluidCSF neopterinHAD patientsMacrophage activationART-mediated viral suppressionCommencement of ARTHigher pre-ART levelsCSF neopterin concentrationsPre-ART levelsProlonged antiretroviral therapySuppressive antiretroviral therapySet-point levelsBlood neopterinHAD subjectsART initiationAsymptomatic HIVTreatment-naïveViral suppressionNeopterin concentrationsImmune activationMost HIVHIV
2008
Persistent Intrathecal Immune Activation in HIV-1-Infected Individuals on Antiretroviral Therapy
Yilmaz A, Price RW, Spudich S, Fuchs D, Hagberg L, Gisslén M. Persistent Intrathecal Immune Activation in HIV-1-Infected Individuals on Antiretroviral Therapy. JAIDS Journal Of Acquired Immune Deficiency Syndromes 2008, 47: 168-173. PMID: 17971711, PMCID: PMC2628632, DOI: 10.1097/qai.0b013e31815ace97.Peer-Reviewed Original ResearchConceptsCSF neopterin levelsHIV-1-infected patientsHIV-1-infected individualsCSF neopterin concentrationsCSF viral loadIntrathecal immune activationAntiretroviral therapyHIV-1 RNACopies/mLNeopterin levelsViral loadNeopterin concentrationsImmune activationCSF HIV-1 RNA loadMost HIV-1-infected individualsPlasma HIV-1 RNA levelsCerebrospinal fluid (CSF) neopterin levelsQuantitative HIV-1 RNAHIV-1 RNA levelsHIV-1 RNA loadCell-mediated immune responsesHIV-1 RNA quantificationHIV-1 concentrationsStable antiretroviral therapySuppressive antiretroviral therapy