2016
HIV Drug Resistance Mutations (DRMs) Detected by Deep Sequencing in Virologic Failure Subjects on Therapy from Hunan Province, China
Chen X, Zou X, He J, Zheng J, Chiarella J, Kozal MJ. HIV Drug Resistance Mutations (DRMs) Detected by Deep Sequencing in Virologic Failure Subjects on Therapy from Hunan Province, China. PLOS ONE 2016, 11: e0149215. PMID: 26895182, PMCID: PMC4760947, DOI: 10.1371/journal.pone.0149215.Peer-Reviewed Original ResearchConceptsDrug resistance mutationsVirologic failureDetection of DRMsPrevalence of DRMsSanger sequencingHIV drug resistance mutationsResistance mutationsART-experienced patientsART-experienced subjectsTreatment-experienced subjectsMedian viral loadNNRTI resistance mutationsStandard genotypingART adherenceViral loadAE subtypeMutation prevalenceDeep sequencingFailure subjectsExperienced subjectsResistant variantsOnly variablePatientsPrevalenceSubtypes
2014
Low-Frequency NNRTI-Resistant HIV-1 Variants and Relationship to Mutational Load in Antiretroviral-Naïve Subjects
Gupta S, Lataillade M, Kyriakides TC, Chiarella J, St. John EP, Webb S, Moreno EA, Simen BB, Kozal MJ. Low-Frequency NNRTI-Resistant HIV-1 Variants and Relationship to Mutational Load in Antiretroviral-Naïve Subjects. Viruses 2014, 6: 3428-3437. PMID: 25256391, PMCID: PMC4189030, DOI: 10.3390/v6093428.Peer-Reviewed Original ResearchConceptsNNRTI resistance mutationsMajor NNRTI-resistance mutationsResistance mutationsAntiretroviral-naïve subjectsARV-naïve HIVMajor NNRTI mutationsNNRTI-resistant variantsTreatment-naïve HIVHIV-1 variantsNon-nucleoside reverseMutational loadNaïve HIVNNRTI mutationsNNRTI resistanceVariant frequencyTrue burdenTherapeutic failureTreatment outcomesTreatment responseAa positionsHIVViral variantsFurther evaluationResistant variantsDeep sequencingPrevalence 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
2012
Virologic Failures on Initial Boosted-PI Regimen Infrequently Possess Low-Level Variants with Major PI Resistance Mutations by Ultra-Deep Sequencing
Lataillade M, Chiarella J, Yang R, DeGrosky M, Uy J, Seekins D, Simen B, St. John E, Moreno E, Kozal M. Virologic Failures on Initial Boosted-PI Regimen Infrequently Possess Low-Level Variants with Major PI Resistance Mutations by Ultra-Deep Sequencing. PLOS ONE 2012, 7: e30118. PMID: 22355307, PMCID: PMC3280244, DOI: 10.1371/journal.pone.0030118.Peer-Reviewed Original ResearchConceptsPI/rDrug-resistant mutationsVirologic failureUltra-deep sequencingR regimenLow-level resistant variantsMajor PI resistance mutationsPI/r regimenResistant variantsARV-naïve subjectsPI-resistant variantsHIV-positive patientsAtazanavir/ritonavirLopinavir/ritonavirM184V/ILow-level variantsPI resistance mutationsMinority of casesTenofovir/RegimenStanford HIVdbResistance mutationsPhenotypic resistanceResistant mutationsStandard genotyping
2011
Prevalence of Low-Level HIV-1 Variants with Reverse Transcriptase Mutation K65R and the Effect of Antiretroviral Drug Exposure on Variant Levels
Kozal MJ, Chiarella J, St John EP, Moreno EA, Simen BB, Arnold TE, Lataillade M. Prevalence of Low-Level HIV-1 Variants with Reverse Transcriptase Mutation K65R and the Effect of Antiretroviral Drug Exposure on Variant Levels. Antiviral Therapy 2011, 16: 925-929. PMID: 21900725, DOI: 10.3851/imp1851.Peer-Reviewed Original ResearchConceptsTreatment-naive individualsDifferent HIV-1 subtypesARV-naive subjectsHIV-1 subtypesAntiretroviral exposureViral loadSubtype CUltra-deep sequencingReverse Transcriptase Mutation K65RRitonavir-boosted protease inhibitorHIV-1 subtype CResistant variantsAntiretroviral drug exposurePlasma viral loadTreatment-naive subjectsLow-level variantsPre-therapy levelsHIV-1 variantsDrug resistance mutationsMutation K65RVirological failureSubtype BDrug exposureMutational loadHigh mutation load
2010
Prevalence and Clinical Significance of HIV Drug Resistance Mutations by Ultra-Deep Sequencing in Antiretroviral-Naïve Subjects in the CASTLE Study
Lataillade M, Chiarella J, Yang R, Schnittman S, Wirtz V, Uy J, Seekins D, Krystal M, Mancini M, McGrath D, Simen B, Egholm M, Kozal M. Prevalence and Clinical Significance of HIV Drug Resistance Mutations by Ultra-Deep Sequencing in Antiretroviral-Naïve Subjects in the CASTLE Study. PLOS ONE 2010, 5: e10952. PMID: 20532178, PMCID: PMC2880604, DOI: 10.1371/journal.pone.0010952.Peer-Reviewed Original ResearchConceptsARV-naïve subjectsVirologic failureUltra-deep sequencingPI TDRsTDR mutationsVirologic successWeek 48Clinical significanceHIV drug resistance mutationsAntiretroviral-naïve subjectsRate of TDRLopinavir/ritonavirM184V/IAtazanavir/ritonavirCase-control studyDrug resistance mutationsSimilar ratesNNRTI TDRCD4 countVirologic responseViral loadControl studyBaseline samplesResistance mutationsBaseline rate
2009
Low-Abundance HIV Drug-Resistant Viral Variants in Treatment-Experienced Persons Correlate with Historical Antiretroviral Use
Le T, Chiarella J, Simen BB, Hanczaruk B, Egholm M, Landry ML, Dieckhaus K, Rosen MI, Kozal MJ. Low-Abundance HIV Drug-Resistant Viral Variants in Treatment-Experienced Persons Correlate with Historical Antiretroviral Use. PLOS ONE 2009, 4: e6079. PMID: 19562031, PMCID: PMC2698118, DOI: 10.1371/journal.pone.0006079.Peer-Reviewed Original ResearchConceptsAntiretroviral treatment historyDrug-resistant mutationsVirologic failureAntiretroviral useDrug-resistant variantsTreatment historyOverall burdenGenotypic resistanceHIV drug-resistant mutationsHIV drug-resistant variantsStanford HIV database algorithmDrug-resistant viral variantsSubsequent antiretroviral regimensTreatment-experienced patientsConventional genotypingPrior treatment historyUltra-deep pyrosequencingSanger sequencingAntiretroviral regimensMore antiretroviralsChart reviewAntiretroviral drugsUltra-deep sequencingClinical implicationsViral variants
2007
Natural Polymorphism of the HIV-1 Integrase Gene and Mutations associated with Integrase Inhibitor Resistance
Lataillade M, Chiarella J, Kozal MJ. Natural Polymorphism of the HIV-1 Integrase Gene and Mutations associated with Integrase Inhibitor Resistance. Antiviral Therapy 2007, 12: 563-570. PMID: 17668566, DOI: 10.1177/135965350701200411.Peer-Reviewed Original ResearchConceptsHIV-1 clade BHIV-1 integrase geneINI-naive patientsStrand transfer inhibitorsHIV-1 integrationGene polymorphismsINI resistanceExcellent virological responseClinical HIV-1Late-stage clinical developmentLos Alamos databaseIntegrase inhibitor resistanceNatural polymorphismsHigh-level resistanceI203MVirological responseClade BClinical trialsHIV-1Aa positionsE138KLate-stage developmentClinical developmentA128TDrug resistance