6533b82bfe1ef96bd128d635
RESEARCH PRODUCT
Detection of drug resistance mutations at low plasma HIV-1 RNA load in a European multicentre cohort study
Mc1 ProsperiN MackieS Di GiambenedettoM ZazziR CamachoI FantiC TortiA SönnerborgR KaiserFm CodoñerK Van LaethemL Bansi Van De Vijver DaAm GerettiA De LucaSehere C. O. N. S. O. R. T. I. U. M. Giacometti AL ButiniR Del GobboS MenzoD TacconiG CorbelliS ZanussiL MonnoG PunziF MaggioloA CallegaroL CalzaM Carla ReR PristeràP TurconiA MandasS TiniA ZoncadaE PaoliniG AmadioL SighinolfiG ZuccatiM MorfiniR ManettiP CorsiL GalliM Di PietroF BartalesiG ColaoA TostiA Di BiagioM SettiB BruzzoneG PencoM TrezziA OraniR PardelliM De GennaroA ChioderaA ScalziniL PalvariniP AlmiG TodaroA D'arminio MonforteP CicconiS RusconiMr GismondoMr GismondoV MicheliMl BiondiN GianottiA CapettiP MeravigliaE BoeriC MussiniM PecorariA SoriaL VecchiM SantirocchiD BrustiaP RavaniniFd BelloN RomanoS MancusoC CalzettiR MaseratiG FiliceF BaldantiD FrancisciG ParrutiE PolilliD SacchiniC MartinelliR ConsoliniL VatteroniA VivarelliD DionisioA NerliL LenziG MagnaniP OrtolaniM AndreoniG PalamaraC FimianiL PalmisanoA De LucaG FaddaVincenzo VulloO TurrizianiM MontanoG CenderelloA GonnelliM ZazziM PalumboV GhisettiS BonoraPd FoglieC RossiP GrossiE SeminariF PolettiV MondinoM MalenaE LattuadaT LengauerM DäumerD HoffmannR KaiserE SchülterC MüllerM OetteS ReuterS EsserG FätkenheuerJ Rockstroh Van De Vijver DaF IncardonaM Rosen ZviT LengauerR CamachoB ClotetA ThalmeV SvedhemG BrattF GargiuloG LapadulaN MancaG ParaninfoE Quiros RoldanG CarosiF CastelnuovoAm VandammeK Van LaethemE Van WijngaerdenJ AinsworthJ AndersonA BabikerD DunnP EasterbrookM FisherB GazzardN GarrettR GilsonM GompelsT HillM JohnsonC LeenC OrkinA PhillipsD PillayK PorterF PostC SabinT SadiqA SchwenkJ WalshV DelpechA PalfreemanD DunnA GlabayK PorterL BansiT HillA PhillipsC SabinC OrkinN GarrettJ LynchJ HandC De SouzaM FisherN PerryS TilburyD ChurchillB GazzardM NelsonM WaxmanS MandaliaV DelpechJ AndersonM KallF PostH KoratC TaylorF IbrahimL CampbellP EasterbrookA BabikerD DunnA GlabayK PorterR GilsonL JamesN BrimaI WilliamsA SchwenkM JohnsonM YouleF LampeC SmithH GrabowskaC ChalonerDi PuradiredjaL BansiT HillA PhillipsC SabinJ WalshJ WeberF RamzanM CarderC LeenA WilsonM GompelsD DooleyA PalfreemanJ AndersonD AsboeA PozniakS CameronP CaneD ChadwickD ChurchillD ClarkS CollinsV DelpechD PillayL LazarusD DunnD DollingE FearnhillH CastroK PorterK CoughlinD DollingM ZuckermanAm GerettiC BoothD GoldbergM GompelsA HaleS KayeP KellamA Leigh BrownN MackieC OrkinD PillayA PhillipsC SabinE SmitK TempletonP TilstonW TongI WilliamsH ZhangD ClarkI Ushiro LumbT OliverD BibbyS MitchellE SmitT MbisaA WildfireR TandyJ ShepherdD ChadwickA MacleanW TongD BennettM HopkinsP TilstonC BoothA Garcia DiazS KayeS KirkP. M. Slootsubject
MaleDrug ResistanceHIV InfectionsDrug resistanceCohort Studies0302 clinical medicineGenotypeHIV InfectionPharmacology (medical)030212 general & internal medicineViral0303 health sciencesProteolytic enzymesGenotypic testing; HIV; Viral load; Adult; Anti-HIV Agents; CD4 Lymphocyte Count; Cohort Studies; Europe; Female; Genotype; HIV Infections; HIV-1; Humans; Male; RNA Viral; Viral Proteins; Drug Resistance Viral; Mutation Missense; Viral Load; Pharmacology; Pharmacology (medical); Infectious DiseasesViral LoadGenotypic testing3. Good healthEuropeInfectious DiseasesCohortRNA ViralFemaleViral loadCohort studyHumanMicrobiology (medical)AdultGenotypeAnti-HIV AgentsMutation MissenseBiologySettore MED/17 - MALATTIE INFETTIVE03 medical and health sciencesViral ProteinsSDG 3 - Good Health and Well-beingDrug Resistance ViralHumansViral ProteinPharmacology030306 microbiologyHIVAnti-HIV AgentVirologyReverse transcriptaseCD4 Lymphocyte CountRegimenHIV; genotypic testing; viral loadGenotypic testing; HIV; Viral load; Adult; Anti-HIV Agents; CD4 Lymphocyte Count; Cohort Studies; Drug Resistance Viral; Europe; Female; Genotype; HIV Infections; HIV-1; Humans; Male; Mutation Missense; RNA Viral; Viral Load; Viral ProteinsImmunologyMutationHIV-1RNAMissenseCohort Studiedescription
Background and objectives: Guidelines indicate a plasma HIV-1 RNA load of 500-1000 copies/mL as the minimal threshold for antiretroviral drug resistance testing. Resistance testing at lower viral load levels may be useful to guide timely treatment switches, although data on the clinical utility of this remain limited. We report here the influence of viral load levels on the probability of detecting drug resistance mutations (DRMs) and other mutations by routine genotypic testing in a large multicentre European cohort, with a focus on tests performed at a viral load <1000 copies/mL. Methods: A total of 16511 HIV-1 reverse transcriptase and protease sequences from 11492 treatment-experienced patients were identified, and linked to clinical data on viral load, CD4 T cell counts and antiretroviral treatment history. Test results from 3162 treatment-naive patients served as controls. Multivariable analysis was employed to identify predictors of reverse transcriptase and protease DRMs. Results: Overall, 2500/16 511 (15.14%) test results were obtained at a viral load <1000 copies/mL. Individuals with viral load levels of 1000-10000 copies/mL showed the highest probability of drug resistance to any drug class. Independently from other measurable confounders, treatment-experienced patients showed a trend for DRMs and other mutations to decrease at viral load levels <500 copies/mL. Conclusions: Genotypic testing at low viral load may identify emerging antiretroviral drug resistance at an early stage, and thus might be successfully employed in guiding prompt management strategies that may reduce the accumulation of resistance and cross-resistance, viral adaptive changes, and larger viral load increases. © The Author 2011. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2011-01-01 |