早期抗HIV病毒治疗英文课件

TowardsanHIVcure Reporter FangZhaoPh D M D DefinitionHIVcure asterilizingcure theeliminationofallHIV infectedcells afunctionalcure thegenerationofeffectivehostimmunitytoHIVthatwouldresultinlifelongcontrolofthevirusintheabsenceoftherapy despitenotachievingthecompleteeradicationofHIV curedfollowinganallogeneicCCR5 32 32haematopoieticstemcelltransplanthassparkedinterestinstudyingcurativeinterventionsintheclinic BerlinPatient TimothyBrown ababyand14adultsare functionallycured AMississippibaby bornwithHIVmorethantwoyearsagoappearstobethefirstdocumentedcaseofachild sbeingcuredofthevirus VISCONTIcohort 14patientswhobeganARTwithin10weeksafterthestartofinfectionandcontinuedforupto3yearsweremorelikelytocontrolHIVreplicationwithoutmedicationsaftersubsequenttreatmentdiscontinuation PLoSPathogens DOI 10 1371 journal ppat 1003211 Veryearlyantiretroviraltreatment i furtherreduceresidualviralreplicationii accelerateimmunerestorationiii preserveinnateimmunityandTbandBcellfunctionsiv limitviraldiversityandviralreservoirs RestingmemoryCD4 Tcellsmonocytesdendriticcellsmacrophageshaematopoieticstemcells viralreservoirs Short CourseAntiretroviralTherapyinPrimaryHIVInfection TheSPARTACTrialInvestigators ShortPulseAnti RetroviralTherapyatSeroconversion NEnglJMed2013 368 207 217January17 2013DOI 10 1056 NEJMoa1110039 ImmunologicdamageafterHIVacquisitionoccursrapidly ashortcourseofARTduringprimaryHIVinfectionpreserveimmunefunction decreaseviralevolutionlimittheviralreservoir Background PrimaryHIVinfectiondefined DefinitiveCriterion 1 apositiveHIV antibodytestwithin6monthsafteranegativetest 2 anegativeHIV antibodytestwithapositivereverse transcription polymerase chain reactionassayforHIVRNA PresumptiveCritrion 3 alowlevelofHIVantibodies opticaldensityunits OD 0 6 accordingtoaserologictestingalgorithmforrecentinfection subtypeBstrainonly 4 anequivocalHIV antibodytestwitharepeattestwithin2weeksshowinganincreaseinthelevelofHIVantibodies5 clinicalmanifestationsofsymptomaticHIVseroconversionillnesssupportedbyantigenpositivityandlessthan4positivebandsonWesternblotanalysis Studydesign 366primaryHIVinfectionfromAugust2003throughJuly2007ineightcountries thefirst6monthsafterHIVinfection median3months Amajority 60 werementhemedianagewas32yearsthemedianCD4countatstudyentrywasapproximately560cells mm3About60 saidtheyhadexperiencedsymptomsofacuteretroviralinfection seroconversion PeoplewhoneededimmediateARTduetolowCD4countorclinicalsymptomsofAIDSwereexcluded Studydesign Participantswererandomlyassigned ina1 1 1ratio toreceiveARTfor48weeks ARTfor12weeks ornotherapy standardofcare Twonucleosidereverse transcriptaseinhibitors NRTIs plusaritonavir boostedproteaseinhibitorwererecommendedClinicvisitswerescheduledatweeks0 4 12 16 and24 andevery12weeksthereafter Follow upcontinuedforamean4 2years TheprimaryendpointswerereachingaCD4countlessthan350cells mm3 apreviousthresholdfortreatmentinitiation orstartinglong termART Studydesign Studydesign Studydesign Results 50 ofparticipantsinthe48 weekARTarmreachedtheprimaryendpoints comparedwith61 inboththe12 weekARTgroupandthestandard of caregroup Thehazardratiowas0 63for48 weekARTversusthestandardofcare asignificantdifference P 0 01 Thehazardratiowas0 93for12 weekARTversusthestandardofcare whichdidnotreachstatisticalsignificance P 0 67 28 ofpatientsinthe48 weekARTgroupsawtheirCD4countfallbelow350cells mm3comparedwith40 boththe12 weekARTandstandard of caregroups Theproportionofpeoplewhostartedlong termtreatmentwassimilarinall3groups 22 21 and22 respectively AposthocanalysisfoundatrendtowardalongerintervalbetweenARTinitiationandtheprimaryendpointswhentherapywasstartedclosertothetimeofseroconversion 48 weekARTwasassociatedwitha0 44logreductioninHIVviralloadat60weeksaftercompletingshort coursetherapy others TherewerenosignificantdifferencesbetweenthegroupswithregardtoprogressiontoAIDS death orseriousadverseevents conclusion A48 weekcourseofARTinpatientswithprimaryHIVinfectiondelayeddiseaseprogression althoughnotsignificantlylongerthanthedurationofthetreatment TherewasnoevidenceofadverseeffectsofARTinterruptionontheclinicaloutcome EnhancedCD4 T CellRecoverywithEarlierHIV 1AntiretroviralTherapy TuanLe M D Dr P H EdwinaJ Wright M D DaveyM Smith M D WeijingHe M D GabrielCatano M D JasonF Okulicz M D JasonA Young Ph D RobertA Clark M D DouglasD Richman M D SusanJ Little M D andSunilK Ahuja M D NEnglJMed2013 368 218 230January17 2013DOI 10 1056 NEJMoa1110187 Background Therelationshipbetweenthetimingoftheinitiationofantiretroviraltherapy ART afterinfectionwithHIV 1andtherecoveryofCD4 T cellcountsisunknown therestorativetimewindow TheintervalbetweentheestimateddateofinfectionandthepeakCD4 countinparticipantswhowerenotreceivingtherapy EarlierARTwasdefinedastheinitiationofARTwithintherestorativetimewindow Viral loadsuppressionwasdefinedasthedocumentationofatleasttwoconsecutiveundetectableplasmaHIVviralloads 75copiespermilliliter Follow uptimes studyset1as48monthsfromtheestimateddateofinfectionoruntilparticipantsbegantoreceiveART studyset2as48monthsfromthedateofARTinitiation untildiscontinuationofARTorlosstofollow up oruntillossofviral loadsuppression Table1 CharacteristicsofStudyParticipantsinStudySets1and2 ARTdenotesantiretroviraltherapy andEDIestimateddateofinfection Results AmongparticipantswhowerenotreceivingART themedianCD4 countatstudyentrywere495cells mm3 CD4countsreachedapeakwithinapproximately4monthsaftertheestimateddateofinfection atamedian763cells mm3 Afterthispoint however CD4countsprogressivelydeclined Results AmongparticipantswhostartedART studyset2 themedianCD4 countbeforetreatmentinitiationwas451cellspercubicmillimeter ARTwasassociatedwitharapidgainofapproximately200CD4 Tcellsandthenaslower sustainedincrease CD4 countscrestedatapproximately900cellspercubicmillimeteratapproximately4monthsaftertheinitiationofARTandthenplateaued Despitethismodestdifference CD4 countsincreasedmorequicklyamongthosestartingARTearlier irrespectiveofwhetherARTwasinitiatedwhentheCD4 countswerehigherorlower conclusion Atransient spontaneousrestorationofCD4 T cellcountsoccursinthe4 monthtimewindowafterHIV 1infection TheinitiationofARTwithinthisearlyrestorativetimewindow whenthehostimmunesystemispoisedforrecovery greatlyacceleratesthepaceandaugmentstheextentofCD4 T cellrecovery EvenafairlyshortdeferralofARTafterclosureofthistimewindowmaycomeattheexpenseofcomprom