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
Predicting Efavirenz Concentrations in the Brain Tissue of HIV‐Infected Individuals and Exploring their Relationship to Neurocognitive Impairment
Srinivas N, Joseph SB, Robertson K, Kincer LP, Menezes P, Adamson L, Schauer AP, Blake KH, White N, Sykes C, Luciw P, Eron JJ, Forrest A, Price R, Spudich S, Swanstrom R, Kashuba A. Predicting Efavirenz Concentrations in the Brain Tissue of HIV‐Infected Individuals and Exploring their Relationship to Neurocognitive Impairment. Clinical And Translational Science 2019, 12: 302-311. PMID: 30675981, PMCID: PMC6510381, DOI: 10.1111/cts.12620.Peer-Reviewed Original ResearchConceptsBrain tissue concentrationsCerebrospinal fluidBrain tissueRhesus macaquesNeurocognitive scoresPK/pharmacodynamic analysesPenetration of antiretroviralsTissue concentrationsExposure-response analysisConcentration-time curveAdult rhesus macaquesCSF AUCEfavirenz concentrationsPlasma AUCPharmacodynamic analysisClinical studiesTissue AUCNeurocognitive impairmentCSF samplesPharmacokinetic dataPK modelingHIVTime pointsAUCNecropsy
2015
Compartmentalized Replication of R5 T Cell-Tropic HIV-1 in the Central Nervous System Early in the Course of Infection
Sturdevant CB, Joseph SB, Schnell G, Price RW, Swanstrom R, Spudich S. Compartmentalized Replication of R5 T Cell-Tropic HIV-1 in the Central Nervous System Early in the Course of Infection. PLOS Pathogens 2015, 11: e1004720. PMID: 25811757, PMCID: PMC4374811, DOI: 10.1371/journal.ppat.1004720.Peer-Reviewed Original ResearchConceptsCentral nervous systemSingle genome amplificationHIV-1 RNA concentrationsHIV-1 replicationInflammatory responseViral replicationHIV-1Nervous systemCSF HIV-1 RNA concentrationsIndependent HIV-1 replicationT-cell-tropic HIV-1Full-length env sequencesART-naïve subjectsCNS viral replicationCSF inflammatory responseTime pointsLocal viral replicationYears of infectionMonths of infectionRNA concentrationViral populationsCellular inflammatory responseCourse of infectionTransmitted variantsPopulation of subjects