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    TuberculosisIntensiveNovember1720,2015

    SanAntonio,TX

    TuberculosisintheHIVPatientLisaY.Armitige,MD,PhDNovember19,2015

    Noconflictofinterests Norelevantfinancialrelationshipswithanycommercialcompaniespertainingtothiseducationalactivity

    LisaArmitige,MD,PhDhasthefollowingdisclosurestomake:

  • 2

    TuberculosisIntensiveNovember1720,2015

    SanAntonio,TX

    TuberculosisintheHIVPatientLisaY.Armitige,MD,PhDMedicalConsultantHeartlandTBCenter

    AssociateProfessorofMedicine/PediatricsUTHealthNortheast

    Epidemiology

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    EstimatedIncidenceofTBper100,000PopulationinAfricanCountriesin1990and2005

    Chaisson R and Martinson N. N Engl J Med 2008;358:1089-1092

    GlobalEpidemiologyofTB

    Global Tuberculosis Report 2014

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    GlobalEpidemiologyofTB/HIV

    Global Tuberculosis Report 2013

    EstimatedHIVCoinfectioninPersonsReportedwithTB,UnitedStates,1993 2014*

    *UpdatedasofJune5,2015.Note:MinimumestimatesbasedonreportedHIVpositivestatusamongallTBcasesintheagegroup.

    % C

    oinf

    ectio

    n

    0

    10

    20

    30

    40

    50

    60

    70

    AllAges Aged2544

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    OutcomesofExposuretoM.tuberculosis

    Inhalation of Droplet Nuclei

    Regional replication in lungs, dissemination

    Killing, clearance of organisms Latent disease Active disease

    ~90% ~5% ~5%

    OutcomesofExposuretoM.tuberculosisinHIVnegativeand HIVpositive patients

    Inhalation of Droplet Nuclei

    Regional replication in lungs, dissemination

    Killing, clearance of organisms Latent disease Active disease

    ~90%~5% reactivationlifetime

    ~5%

    10% reactivation per year

    Up to 36% active disease

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    Signs&SymptomsPulmonaryTB

    PulmonarySymptoms:

    Productive,prolongedcoughofover3weeksduration

    Chestpain Hemoptysis

    SystemicSymptoms:

    Fever Chills Nightsweats Appetiteloss Weightloss Easyfatigability

    TestingforTBInfection TST

    Thetuberculinskintest(TST)mayhelpdifferentiateinfectedfromuninfectedpeoplewithsignsandsymptoms

    AnegativeTSTdoesnotexcludethediagnosisofTB(especiallyforpatientswithsevereTBillnessorinfectionwithHIV)

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    ClassifyingtheTuberculinReaction

    5mmisclassifiedaspositivein

    HIVpositivepersons

    RecentcontactsofTBcase

    PersonswithfibroticchangesonchestradiographconsistentwitholdhealedTB

    Patientswithorgantransplantsandotherimmunosuppressedpatients

    Diagnosis

    Clinical Microbiology and Infection, Volume 10 Number 5, May 2004

    **

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    IFN (gamma)releaseassays(IGRAs)

    www.cellestis.com

    AntigensforGammaReleaseAssays

    www.cellestis.com

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    FDAapprovedIGRAs

    QuantiferonGoldInTube(IT)

    TSPOT.TB

    Quantiferon GoldInTube

    PLoS ONE June 2008 Volume 3 (6): e2489

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    ELISPOT

    S. A. Clark et al. 2007. Clinical and Experimental Immunology

    Poorconcordancebetweeninterferonreleaseassaysandtuberculinskintestsindiagnosisoflatenttuberculosisinfection

    amongHIVinfectedindividualsBMCInfectiousDiseases2009,9:15

    Crosssectionalstudyin2HIVclinicsinAtlanta,Georgia(n=336),85%black,65%male,91%USborn,69%onHAART,60%withahistoryofanOI.

    MedianCD4=334,medianviralload400copies/ml

    Conclusion: WefoundalowprevalenceofLTBIandpoorconcordancebetweenall3diagnostictests(TST,

    QFIT,TSPOT.TB).

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    373HIV+patientsreceivedall3tests Demographics:

    50%IVDU, 74.5%onART, 16.6%withCD4count

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    Roleofinterferongammareleaseassaysinthediagnosisofpulmonarytuberculosisinpatients

    withadvancedHIVinfectionCattamanchi etal.BMCInfectiousDiseases2010,10:75

    **

    Allpatientswhocouldproduceasputumscreened 881patientsenrolled,70.9%HIVpositive CultureconfirmedTBin201 HIVpatients:

    88.2%sensitivityoverall 74.7%sensitiveinculture+,smearnegativespecimens

    Clinical Infectious Diseases 2012;55(9):11718

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    Tuberculosis Research and TreatmentVolume 2012, Article ID 932862

    Tuberculosis Research and TreatmentVolume 2012, Article ID 932862

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    CXR HIVinfectedpersons

    Maycauseinfiltrateswithoutcavitiesinanylungzone

    Maycausemediastinal orhilarlymphadenopathywithorwithoutinfiltratesorcavities

    InHIVinfectedpersonsalmostanyabnormalityonCXRmayindicateTB

    ComparisonofevaluationtoolsfordiagnosisofTBinHIVpatients SOCscreeningalgorithm:cough,fever,weightloss,nightsweatsinprevious30days,sputumsmear,

    CXR(ifnotpregnant) Expandedassessmenttooladdedothersymptomstoscreening(GI,GU,neuro,derm)and

    fluorescentmicroscopy

    801patients,average33y/o,medianCD4275

    Results: 51%withTBhadanormalCXR SOCsensitivity54%,specificity76%,PPV24%,NPV92% Coughwasthemostsensitivesymptom(especiallywhencombinedwithabnl CXR,LN,orCD4count

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    Drivenmostlybydegreeofimmunity

    HIVpositivepatientsaremorelikelytohave: Isolatedextrapulmonarylocalization(5363%insomestudies) Primaryinfection Pulmonarybasilarinvolvement Tuberculouspneumonia Hilarormediastinallymphadenopathies MiliaryordisseminatedTB NormalCXR(820%insomestudies)

    ClinicalPresentationHIVpositivevs.HIVnegativepatients

    Clinical Microbiology and Infection, Volume 10 Number 5, May 2004

    PrimaryTuberculosis

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    MiliaryTuberculosis

    TuberculosisandHIV

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    AnAlgorithmforTuberculosisScreeningandDiagnosisinPeoplewithHIV

    NEngl JMed2010;362:70716.

    Bacteriologicorhistologicexam

    Sputum Three(824hoursapart,atleastonefirstthinginthemorning)

    Tissue Lymphnodebiopsy Bonemarrowbiopsy

    Otherspecimens Urine CSF Peritonealfluid Pleuralfluid(pleuralbiopsy)

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    Diagnosis Summary

    Musthaveahighindexofsuspicion

    Mustutilizemanypiecesofinformationinmakingthediagnosis

    TBcanpresentverydifferentlyinHIVinfectedpatientswhencomparedtoHIVnegativepatients

    TestingforTBInfectionSomePrinciplestoConsider

    Individualswhohavea +TSTresult, a+IGRAresultor symptomssuggestiveofTB(regardlessofTST/IGRAresults)

    shouldbeevaluatedwithanchestxray

    PatientswithHIVwhomaynotreacttotestingbyTSTorIGRAshouldhaveachestxrayifTBissuspectedorifexposedtoanactiveTBcase

    Ifabnormalitiesarenoted,ortheclienthassymptomssuggestiveofextrapulmonary TB,additionaldiagnostictestsshouldbeconducted

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    HIVinfectedpersons,regardlessofage,shouldbetreatedforLTBIiftheyhavenoevidenceofactiveTB andexhibitthefollowingcharacteristics:

    1)apositivediagnostictestforLTBIandnopriorhistoryoftreatmentforactiveorlatentTB(AI);

    2)anegativediagnostictestforLTBIbutareclosecontactsofpersonswithinfectiouspulmonaryTB(AII);and

    3)ahistoryofuntreatedorinadequatelytreatedhealedTB(i.e.,oldfibroticlesionsonchestradiography)regardlessofdiagnostictestsforLTBI(AII)

    GuidelinesforPreventionandTreatmentofOpportunisticInfectionsinHIVInfectedAdultsandAdolescents,MMWR2009

    RiskreductionbytreatmentofLatentTBInfection(LTBI)inHIVinfectedpatients

    Churchyardetal. JID2007:196(Suppl 1)S52

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    BeforeinitiatingtreatmentforLTBI RuleoutTBdisease

    i.e.waitforcultureresultsifspecimenobtained

    DeterminepriorhistoryoftreatmentforLTBIorTBdisease

    Assessrisksandbenefitsoftreatment

    Determinecurrentandpreviousdrugtherapy

    InitiatingTreatmentforLTBI

    IsoniazidRegimensforLTBI

    9monthregimenofisoniazid(INH)isthepreferredregimen

    6monthregimenislesseffectivebutmaybeusedifunabletocomplete9months

    Maybegivendailyorintermittently(twiceweekly) Usedirectlyobservedtherapy(DOT)forintermittentregimen

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    Personswiththefollowingconditionsneedspecialprecautionswhileonisoniazid

    a. Age35yearsandoverb. Takingothermedicationsonalongtermbasisc. Alcoholabusersd. Historyofpreviousdiscontinuationofisoniazidbecauseof

    toxicity/adversereactionse. Chronicliverdiseasef. Peripheralneuropathyg. Pregnancy

    RifampinRegimensforLTBI

    Rifampin(RIF)givendailyfor4monthsisanacceptablealternativewhentreatmentwithINHisnotfeasible.

    InsituationswhereRIFcannotbeused(e.g.,HIVinfectedpersonsreceivingproteaseinhibitors),rifabutinmaybesubstituted.

    RIFandPZAfor2monthsshouldgenerallynotbeofferedduetoriskofsevereadverseevents6

    6MMWR August 8, 2003; 52 (31): 735-739

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    LTBItreatment

    MMWRAugust8,2003/Vol.52/No.31

    3HPRegimenandHIVpatients

    12weekregimenofINHandRifapentine dosedonceaweek

    ContraindicatedinpatientsonANYantiretrovirals

    AcceptableifnotonHIVmedications

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    Purpose 1 5.RecommendedTreatmentRegimens 36

    WhatsNewInthisDocument 1 CONTENTSOF 6.PracticalAspectsofTreatment 42

    Summary 1 THE80Page 7.DrugInteractions 45

    1.IntroductionandBackground 13 Document 8.TreatmentinSpecialSituations 50

    2.OrganizationandSupervisionofTreatment 15 9.ManagementofRelapse,TreatmentFailure,andDrugResistance

    66

    3.DrugsinCurrentUse 19 10.TreatmentofTuberculosisinLowIncomeCountries:RecommendationsandGuidelinesoftheWHOandtheIUATLD

    72

    4.PrinciplesofAntituberculosisChemotherapy 32 11.ResearchAgendaforTuberculosisTreatment 74

    UpdatesandChangesinTherapy

    Changesindosingschedules:

    HIV+individualswithlowCD4counts shouldNOTbegiventwiceweeklytherapy

    Rifabutin (RBT):Maybeusedasaprimarydrugforpatients(especiallyHIV+)receivingmedicationshavingunacceptableinteractionswithrifampin(e.g.ProteaseInhibitors,methadone)

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    MorbidityandMortalityWeeklyReportJune20,2003/Vol.52/No.RR11

    ATSrecommendationsfortreatmentoftuberculosis

    **

    TreatmentofMTBinHIV(+)Pts

    VitaminB6shouldbeaddedforallHIV(+)pts

    Da