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TuberculosisIntensiveNovember1720,2015

SanAntonio,TX

TuberculosisintheHIVPatientLisaY.Armitige,MD,PhDNovember19,2015

Noconflictofinterests Norelevantfinancialrelationshipswithanycommercialcompaniespertainingtothiseducationalactivity

LisaArmitige,MD,PhDhasthefollowingdisclosurestomake:

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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

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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