Optimal Timing and Duration of Induction Therapy for HIV-1 Infection 英文参考文献.docVIP

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Optimal Timing and Duration of Induction Therapy for HIV-1 Infection 英文参考文献.doc

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Optimal Timing and Duration of Induction Therapy for HIV-1 Infection 英文参考文献

OptimalTimingandDurationofInduction TherapyforHIV-1Infection Marcel E.Curlin1,2,Shyamala Iyer2,John E.Mittler2* 1 Department of Medicine, University of Washington, Seattle, Washington, United States of America, 2 Department of Microbiology, University of Washington, Seattle, Washington,UnitedStatesofAmerica Thetradeoffbetweentheneedtosuppressdrug-resistantvirusesandtheproblemoftreatmenttoxicityhasledtothe developmentofvariousdrug-sparingHIV-1treatmentstrategies.Hereweuseastochasticsimulationmodelforviral dynamics to investigate how the timing and duration of the induction phase of induction–maintenance therapies mightbeoptimized.Ourmodelsuggeststhatunderavarietyofbiologicallyplausibleconditions,6–10moofinduction therapyareneededtoachievedurablesuppressionandmaximizetheprobabilityoferadicatingvirusesresistanttothe maintenanceregimen.Forinductionregimensofmorelimitedduration,adelayed-inductionor-intensificationperiod initiatedsometimeafterthestartofmaintenancetherapyappearstobeoptimal.Theoptimaldelaylengthdependson thefitnessofresistantvirusesandtherateatwhichtarget-cellpopulationsrecoveraftertherapyisinitiated.These observations have implications for both the timing and the kinds of drugs selected for induction–maintenance and therapy-intensificationstrategies. Citation: CurlinME,IyerS,MittlerJE(2007)Optimaltiminganddurationofinduction therapyforHIV-1 Infection. PLoSComput Biol3(7):e133. doi:10.1371/journal.pcbi. 0030133 tution of induction therapy [23]. One weakness of existing studieshasbeenthatinductiontherapyconsistedofstandard Introduction The failure of antiretroviral therapies to completely suppress viral replication in some patients represents a major dif?culty in the management of HIV infection. In therapy-naivepatientswithoutclinicallyapparentresistance mutations, triple-drug therapy with two nucleoside–analog reversetranscriptaseinhibitorsandaproteaseinhibitorora non-nucleosidereversetranscriptaseinhibitorisstandard[1]. Inthesepatients,treatme