HIV-TB Coinfection | Jindal chest clinic

HIV weakens the immune system, increasing the risk of TB in people with HIV. Infection with both HIV and TB is called HIV/TB coinfection. This presentation is an overview on "HIV-Tuberculosis Coinfection"

1. Dr. S. K. Jindal
www.jindalchest.com

2. ISSUES
Magnitudeofproblem
ImmunologyofTB
Effectofco-infection
Clinicalmanifestations
Roleofmoleculardiagnostics
Treatmentguidelines

3. Resurgence of TB
1982 1995
60
30
19911986
TB notification rate per
lakh
0

4. Magnitude :HIV burden
WHO region HIV inf TB Prev. Coinfection
Africa 18.7M 48% 9M
SEA/W pacific 6.0M 40% 2.4M
Americas 1.3M 30% 0.4M
East Mediteran 0.18M 23% 0.04M
Europe/USA 1.35M 11% 0.15M

5. Global Scenario
13-14millionco-infectedwithHIVandTB
In2003,estimated9%(~700000)ofallnewTBcases(8.8m)wereHIVpositive
InsomeregionsofAfrica,75%ofTBpatientsareHIV-infected
In2003,estimated15%(~230000)ofallTBdeaths(1.7m)wereHIVpositive
EffectofHIVonTBismoststrikinginAfricawhere29%ofTBisattributableto
HIV
RisingTBincidenceinAfricaisoffsettingthestableorfallingTBincidenceinthe
restoftheworld
(GlobalTBincidencecontinuestoriseby1%perannum)

6. Indian Scenario
TBSituation
Estimated40%populationinfected
1.8millionnewTBcasesannually
IncidenceofTBishigherinnorth
Estimatedupto5%ofTBpatients
areHIVpositive
HIVSituation
HIVprevalenceingeneral
population<1%
50-60%HIVinfectedare
expectedtodevelopTB
PrevalenceofHIVhigherinsouth
TBisleadingcauseofdeathsin
peoplewithHIV

7. 10
60
0
10
20
30
40
50
60
70
PPD+/HIV - Negative PPD+ / HIV+
Percentage TB and AIDS
Lifetime Risk of TB

8. Mechanisms of Coinfection
Impairmentofimmuneresponse
Progressivedepletion&dysfunctionofCD
4lymphocytes
Impairedmacrophagefunction
Invasionofinflamedbronchialwalls–thebreedingsites

9. Tubercle bacilli
Alveolar
macrophages
CD4 T cell
IFN Gamma
Activated
macrophages
Increased viral
replication
in monocytes
T cells
Potentiationof HIV replication
IL1/ TNF a
Induces n FKB
which binds promoter
region of HIV

10. Augmented Effects
HIVonTB
Rapidprogression
Activedisease(40%)
Highermorbidity
Mortality:4timeshigher(thanHIV–ve),20-35%
IncreasedADRstoATT
Increaseddrugresistance
TBonHIV
Increasedviralreplication,load,immunesuppression,infections,
morbidityandmortality

11. How does TB occur?
1.Endogenousreactivation
•HIVismostpotentriskfactor
2.Exogenous(Re)infection
•IncreasedchancesofTBexposureinhospitals

12. Clinical Features
Earlystage(CD
4>200/mm
3
)
•TypicalreactivationTB
•(Upperlobesinfiltrates/cavities)
Advancedstage(CD
4<200/mm
3
)
•Atypicaldisease
•Disseminated/extrapulmonaryTB

13. Clinical Presentation, Symptoms
Fever,cough,chestpain,weightloss
Chronicdiarrhoea
Generalizedlymphadenopathy
Organspecificsymptomsandsigns

14. Atypical Manifestations (Pulmonary)
Lowerlobe/diffuseinvolvement
Absenceofcavityformation
Endobronchialinvolvement
Prominenthilar/mediastinal
Pleuraleffusion–common
MiliaryTB
Chestwallabscess/cutaneoussinuses

15. Clinical & ImmunopathCourse
HIV-Related TB
Median CD4 count (mm
–
3
)
100
0
200
300
400
500
Duration of HIV infection
Density of bacilli in lesions
PTB Nodal,
serous
TB
TBM MTB
+
+
+
+
DeCocket al, JAMA 1992

16. Clinical featureHIV negative Early HIV Advanced HIV/AIDS
Tuberculin
reactivity >10mm
75-85% 40-70% 10-30%
Chest X Ray 50-70%
typical(UL
fibronodular
lesions)
50% cavities
Mixed typical
and atypical
Increased adenopathy
effusions,LZone inv
miliaryinfiltrates
Reduced Cavitation
Sites InvolvedPulmonary 80%
Extra pulmonary
16%
Both 4%
IntermediatePulmonary 20-30%
Extrapulm20-50%
Both 30-70%
Sputum smear
positivity
70-80% ~50% 30-40%
Clinical features: TB with HIV

17. ExtrapulmonaryTB
LYMPHATIC
Commonestextra-pulmonarysite
Peripheral
Intrathoracic
Intra-abdominalwithnecrosis
(accompanyingvisceralinvolvement)
DISSEMINATED
MiliaryormorethanoneXPsite
Mycobacteremia
SKIN
Mayco-existwithpulmonaryTB
Erythematouspapules,purpura,
subcutaneousnodules,pustules
Biopsy-littlegranuloma,AFB+
HEPATOSPLENIC
Round,hypoechoic,multiplelesions<1cm
TBMENINGITIS
CSFfindingsmaybenormal
LARYNGEAL

18. Atypical manifestations
Sputumsmearsnegativedespiteextensiveinvolvement
Normalchestxrays&sputumpositiveforAFB–endobronchialTBor
mycobacteremia
Mycobacteriamaybeisolatedfromblood,marrow,urine&fluids
Lymphnodeaspirate/Bx-poorlyformedgranulomas,focalareasof
necrosisteemingwithAFB

19. TB Lymphadenitis
Size>4cm
Rapidenlargement
Asymmetrical
Tender/Painful;nolocalinfection
Matted/fluctuant
Presenceofconstitutionalsymptoms
Maybeacute–resemblepyogeniclymphadenitis

21. Unusual Manifestations
Massiveabd.lymphadenopathy
Hemophagocytosissyndrome
Bronchoesophagealfistula
Multiplevisceral/brainabscesses
Cutaneous,softtissueabscess
Osteomyelitis
Sepsiswithsepticshock

22. HIV related TB in Children
FeaturesofHIVinfection:
Wt.loss,slowgrowth
Ch.Diarrhoea(>1month)
Prolongedfever
GeneralizedL.N.enlargement
Recurrentear,throatinfection
Oropharyngealcandidiasis
Persistentcough
DisseminatedTB
ExtrapulmonaryTB

23. Series HIV negative Early HIV
CD 4>200
Advanced HIVAIDS
Abouyaet al
Ivory Coast
1990-92
Cavitary56%
Noncavitary42%
HilarLNE 2%
Miliary2%
Effusions 4%
53%
39%
8%
3%
8%
29%
58%
20%
9%
11%
Batungwanyo et
al Rwanda
1988-89
Cavitary 91%
Upper lobe 55%
Hilar LNE 0%
Miliary 9%
Effusions 9%
69%
30%
7%
23%
46%
28%
16%
40%
26%
42%
Radiologic features in HIV-TB

24. CxRFindings in TB Patients
with HIV Infection
Early HIV
Late HIV
(severely immuno-compromised)
Source: Various references including WHO Clinical Guide; Allen AM, NamaamboK, Allen BW, et al. Negative sputum
smear results in HIV-positive patients with pulmonary tuberculosis in Lusaka, Zaire. TubercLung Dis1993;74:191-94.

32. Tuberculin skin testing
TuberculinreactivityfourfoldlessinHIVinfection
Reactivitydeclineswithincreasingimmunesuppression
-EarlyHIV40-70%
-AdvancedHIV10-30%
AnnualtuberculintestingforHIVinfectiontodetectlatentinfection
Tuberculinanergyassoc.withriskofactiveTBiscontroversial

33. Tuberculin skin testing
Thereactiondeclineswithimmunesuppression,5mmindurationis
consideredsignificantinHIVinfection(CDC/ATS)
(Somehaveadvocatedreducingto2mm)
Recommendedtogiveprophylactictherapyinsuchcasestopreventdisease
Closecontactsofinfectiouscasesandpopulationswithhighpriorprobability
ofTBarealsorecommendedtobegivenprophylactictherapy

34. Role of FOB
Valuableinearlydiagnosis
DiagnosisofendobronchialTB
TBLByieldisgreater(82%)thanBAL(26%)
MiroetalChest,1992
TBNAhasaroleinmediastinallymphnodaltuberculosiswithnegative
sputumsmears
HarkinetalAmJRespCritCareMed,1998

37. Molecular diagnosis: RFLP
IdentifythespecificstrainsofMycoTBbypatternofgenefragments
Hasshownthatrecentinfectionisresponsibleforupto50%TBcasesinboth
HIVnegativeandHIVinfected
UsedtoconfirmthatclusterofTBcasesarelinkedbyrecenttransmission
especiallyduringnosocomialoutbreaks
HalvirDV,BarnesPFNEnglJMed1999

38. MANAGEMENT
TreatmentofTuberculosis
ManagingViralinfection
Druginteractions/Adversereactions
Paradoxicalreactions
MDR/XDR-Tb
Chemoprophylaxis
BCGvaccination

39. HIV related TB management
RNTCPschedule
Evaluateforotherinfections
Startcotrimoxazoleprophylaxis
Nutrition
Screeningoffamily
Screenforside-effects
Considerationforanti-retroviraldrugs

40. HIV & Tb: Treatment
Durationoftreatment:6months(2HREZ/4HR)
Rifampicincontra-indicatedwithPI/nevirapinecontainingHAARTregimens
PossibleoptionsforARTinpatientswithactiveTB:
DeferARTuntilTBtreatmentiscompleted
DeferARTuntilthe‘continuationphase'oftreatmentforTB,anduseHE
ascontinuation.
TreatTBwithRIFcontainingregimenanduseEfavirenz+2NRTIs

41. Tuberculosis and ARV Therapy
Status When to Start ARV Therapy
CD4 less than 200/mm
3
Start TB Therapy
Start ARV as soon as TB therapy can be
tolerated
CD4 between 200 and 350/mm
3
Start TB therapy
Start ARV therapy after 2 mo. Of TB
therapy with EFV
CD4 greater than 350/mm
3
Treat TB, start ARV therapy according to
general indications

42. ART drug Classes
Nucleosidereversetranscriptaseinhibitors(NRTI)
Nonnucleosidereversetranscriptaseinhibitors(NNRTI)
Proteaseinhibitors(PI)
Fusioninhibitors

43. Life cycle of HIV

44. Drug interactions
UseofRifampicinwithPI/NNRTIbasedARTiscontraindicated.
NRTIarenotmetabolizedbyhepaticcytochromeP450enzymesystem
hencetheycansafelybeusedwithRifampicinbasedATT
OtherfirstlineATT(SHEZ)nointeractionswithARTandcanbeused
safely:SHEZx2monthsfollowedbySHZx7months

45. Drug interactions
Rifabutin:lesspotentinducerandcanbeusedinplaceofRifampicinin
ATTwithPINNTRIbasedART(equivalentbactericidalaction,clinical
curerates)
RitonavirretardsRifabutinmetabolism(levels35fold)toxicreactions–
uveitis,neutropenia,arthralgiaoccur.combinationiscontraindicated

46. Management strategies

47. Initiation of Antiretroviral Therapy for Patients with TB:
To Start or to Delay?
ReasonstostartART
DecreasemorbidityandmortalityrelatedtoHIV/AIDS
ReasonstodelayART
-OverlappingsideeffectsfromARTandanti-TBtherapy
-Complexdrug-druginteractions
-Immunereconstitutioninflammatorysyndrome(paradoxicalreactions)
-Difficultieswithadherencetomultiplemedications
-Pillburden

48. HIV –MDR/ XDR TB
Poorimmuneresponseleadstoincreasedrapidlydividingbacilliand
spontaneousmutations
NoncomplianceduetofrequentADR
Largepillburden
MalabsorptionofATT
UseofRifabutinprophylaxisforMAC

49. Adverse drug reactions
MorefrequentlyinHIVinfected,20-25%
Relatedtolevelofimmuneactivationandimmunesuppression
Thiacetazoneinducedexfoliativedermatitis,TEN,StevenJohnson
syndromecanbefatal(contraindicatedwithHIV)
ATTinducedhepatitisfourfoldhigherthanseronegativepatient
Riskfactors-anergy,lymphopenia,ElevatedNeopterinlevels

50. Therapy outcomes
EarlyclinicalandmicrobiologicalresponsesimilartoHIVnegativepatients
withTB
Relapserateshigherindevelopingworldthaninthedevelopednations
DataconflictingabouthigherrateofrelapseinHIVinfectedthanHIV–ve.
CDCguidelines,MMWR,Oct1998

51. Recommendations
CDC/ATSrecommendation:6monthsATTwithdrugsensitiveTB&
prolongationto9monthsifslowclinical/microresponse
Factorsassocwithpooroutcome–advancedimmunesuppression,
noncompliance,delayedclinical/microbiologicalresponsephysicianshould
prolongdurationofATT

52. Paradoxical reaction
Definedastemporaryworseningofclinicalcondition,appearanceofnew
radiologicmanifestationsafterinitiationofTt,andarenotduetoTtfailureor
asecondprocess
DuetorecoveryofimmunologicalTh1responsetomycobacterialantigen
Heightenedgranulomatousresponsemaycleartheorganismbutitselfmay
causetissuedamage

53. Paradoxical reation: Clinical findings
Hecticfever,peripheral/mediatinallymphadenopathy,miliaryinfiltrates,
pleuraleffusion
Worseningoforiginallesions:pulmonaryinfiltrates,tuberculomasmaybe
lifethreatening
Selflimited,usuallylasts10-40days

54. Mimickers of PDR
Treatmentfailure
Drugresistance
Noncompliance
Drugfever
DevelopmentofanotherOI
ConditionnotrelatedtoTBorHIV

55. “Heart attacks”
IncidencewithATTalone~7%withART+ATT~36%
SubstantialreductioninviralloadandincreaseinCD4countsfound(
immunereconstitution)
Increasedtuberculinreactivitynoted
StrongerimmuneresponsetoMycobactTBresultsinPR
KunimotoetalIntJTubercLungDis1999

56. Treatment of PDR
RarelyrequiresstoppingATT/HAART
RequiresNSAIDforsymptomaticrelief
Forlifethreateningstates:shortcoursesteroidsmaybegivetosuppress
inflammationwhileATTandARTarecontinued

57. Chemoprophylaxis
LatentinfectioninHIVpatients(TST>5mm)mustbetreatedtoprevent
diseaseandspreadincommunity.
INHdailyx9months
Rifabutin+PZIdailyx2mths(OnART)
Rifampicin+PZIdailyx2mths(NoART)
Rifampicindailyx9months

58. Chemoprophylaxis
Rifampicinregime-INHresistantstrain,intolerance,poorcompliance
InIndia,INHresistanceissignificanttheuseofcombinationdrugsis
advised
ForHIVpositivecontactsofMDRTB
PZI+Flouroquinolonedailyx12months
PZI+Ethambutoldailyxmonths
WHOdoesnotrecommendCPinregionwhereprevalenceishigh

59. Problems with Preventive Chemotherapy
o Ensuring certainty to exclude active tuberculosis
o Efficacious but inefficient
o Rare adverse drug events
o Difficulties in ensuring adherence

60. Role of BCG
ContraindicatedwithpersonswithadvancedHIVdisease/AIDSbecauseof
riskof“disseminatedBCGiosis”
ButincountrieswhereriskofTBishigh,WHOrecommendsBCGshould
begivenassoonafterbirth.
DisseminatedBCGiosistreatedwithINH+Rifampicin

61. Conclusions I
TB-HIVcoinfectionisacommonoccurrence
TBoftenprecedesotherAIDSdefiningillnesses
Clinicalpresentationdependsonlevelofimmunefunction
Symptomsareusuallynonspecific
ExtrapulmonaryTBiscommon

62. Conclusions II
ScreenallcasesofTBforHIVinfection
InitiateATTwithDOT
Consideroptimalantiretroviraltherapy
UnderstanddruginteractionsofRifamycinswithPI/NNRTIbasedART
Observeforparadoxicalreactions
Identifydrugresistanttuberculosis

63. Conclusion III
Likely impact of HIV on TB in India?
ScenariowithoutRNTCP
HIVwouldincreaseTBprevalence(by1%),incidence(by12%),andmortalityrates(by
33%)between1990and2015
ScenariowithRNTCP
Expectsubstantialreductionsinprevalence(by68%),incidence(by41%),andmortality(by
39%)between1990and2015
Nationally,RNTCPshouldbeabletoreversetheincreasesinTBburdenduetoHIVbut,to
ensurethatTBmortalityisreducedby50%ormoreby2015,HIV-infectedTBpatientsshould
beprovidedwithantiretroviraltherapyinadditiontotherecommendedtreatmentforTB
Methodology:MathematicalmodelingusingdatafromHIVsentinelsurveillance,studiesonTB
prevalenceandincidence,andRNTCPnotificationdata
Ref:Williamsetal.TheimpactofHIVAIDSonthecontroloftuberculosisinIndia.ProceedingsofNationalAcademyofSciences(US)July5,2005vol.102
no.279619–9624

64. WHO Recommendations 2002

65. Pulmonary Tuberculosis in HIV-Infected Patients in Zaire —A
Controlled Trial of Treatment for Either 6 or 12 Months
After6months(2HREZ/4HR)
Treatmentfailureratessimilar:3.8%and2.7%(p=0.70)
At24months,theHIV-seropositivepatientswhoreceivedextendedtreatment
hadarelapserateof1.9%vs.9.0%amongtheHIV-seropositivepatientswho
receivedplaceboforthesecond6months(P<0.01)
RelapseamongtheHIV-seronegativepatients:5.3%
Extendedtreatmentdidnotimprovesurvival
Perriëns JH et al. NEJM 1995;332:779-785

66. Revised National TB Control Programme
(RNTCP)
Following1992review,RNTCPdesignedbasedoninternationallyrecommended
DOTSstrategy
DOTSisafive-pointstrategytocontrolTB:
Politicalandadministrativecommitment
Diagnosisprimarilybysputummicroscopy
Uninterruptedsupplyofgoodqualitydrugs
DirectlyObservedTreatment(DOT)
Standardizedrecording,reportingandmonitoring
RNTCPstartedonapilotscalein1993
Scalingupasnationalprogrammestartedin1997

67. RNTCP –Objectives
Toachieveandmaintainacasedetectionofatleast70%ofnewsputum
positiveTBpatients
Toachieveandmaintainacurerateofatleast85%insuchpatients

68. Referral from VCTC/ ART clinic to RNTCP
ThinkTBif:
Cough>3weeksduration
Unexplainedfever
Lossofweight
Haemoptysis
Enlargedlymphnodes
SuspicionofTBatothersites

69. RNTCP Drug Regimens: Treatment Outcome
HIV/AIDS and TB
69
HIV & PTB Patients: 95
Culture Positive PTB: 66
New: 46 Old: 20
Cure Rate 92% 83%
Mortality 42%
Source: TRC –GHTM, Tambaram Pilot Study

70. A Review of Efficacy Studies of 6-Month Short-Course Therapy for
Tuberculosis Among Patients Infected with HIV
HIV + (%) HIV-(%)
Cure 59.4 –97.1 62.3 –88.0
Relapse 0.0 –10.0 0.0 –3.4
Treatment success 34.0 –100 91.2 –98.8
Treatment
effectiveness
29.4 –88.2 70.6 –83.8
El-SadrW et al. ClinInfect Dis2000;32:623-632

71. TB Mortality & Recurrence
65%diedin40monthf/uperiod,40%by2years.
Of31patientswhocompletedafullcourseof
regularanti-TBtherapyandwerefollowedupto
24months,12hadarecurrence(39%)
DNAfingerprintingdoneonpre-treatmentand
relapseculturesusingIS6110andDRprobes.
All8pairsofculturesthatwerefingerprintedhad
anewstrainofMycobacteriumtuberculosisre-
infection)attimeofrecurrence.
TRC –GHTM, TAMBARAM PILOT STUDY; 11
th
CROI, 2004

72. VCTC –RNTCP cross-referrals
VCTCclients(irrespectiveofHIVstatus)screenedforTBsymptomsandreferredto
RNTCPdesignatedmicroscopycentres(DMC)
AtDMCallsuchreferralsarescreenedforTBandthosediagnosedwithTBdisease
areputonDOTStreatment
RNTCPstaffcommunicatetoVCTCstaffaboutTBdiagnosisandtreatmentofall
referredclients
VCTCstaff,onthebasisofinformationreceivedfromRNTCP,generatemonthly
disaggregateddata,basedonHIVstatus
ConfidentialityofHIVstatusisnotbreached
SimilarlyTBcaseswithhistoryofhighriskbehaviour,STD,oranyotherOI,are
referredtothenearestVCTC

73. How are patients treated?
Standardintermittentregimenwith3categoriesoftreatment
TreatmentunderdirectobservationofaDOTprovider(DP)
EntirecourseofdrugspackagedinaPatientWiseBox(PWB)
CategorydecidedbyMO(CatI/II/III)
Treatmentstartedaftercounseling,addressverification,identificationofDOT-Provider
&transportationofPWBtoDP
DrugstobetakenthreetimesaweekunderdirectobservationoftheDP
Intensivephase(2-3months)-alldosesgivenunderobservation
Continuationphase(4-5months)-firstdoseoftheweekgivenunderobservation
Dosesarerecordedontreatmentcards
Ifpatientmissesanydose,homevisitmadeimmediatelytoretrievepatient

74. TB/HIV collaborative activities
National,StateandDistrictlevelcoordinationcommitteesestablishedand
meetingsheld
Guidelinesandtrainingmaterialdevelopedjointly
On-goingtrainingofstaffonTB/HIV
Cross-referralbetweenVCTandDOTSservicesdeveloped,pilotedand
implemented
InvolvementofNGOsandPPs
CollaborativeIECactivities
Jointmonitoringofactivities

75. Diagnosis of Pulmonary TB
Cough 3 weeks
AFB X 3
Broad-spectrum antibiotic 10-14 days
If symptoms persist, repeat AFB smears, X-ray
If consistent with TB
Anti-TB Treatment
If 1 positive:
CxR and
evaluation
If 2/3 positive:
Anti-TB Rx
Ifnegative:
Source: Global Tuberculosis Control: WHO Report 1999 (WHO/TB/99.259) and World Health Organization. Treatment of tuberculosis.
Guidelines for national programs. (Second Edition.) WHO/TB/97.220,1997.

76. Treatment Categories
TB treatment TB Patients category
I
II
III
•Newsmear-positivepulmonaryTB
•Newsmear-negativepulmonaryTBwithextensiveparenchymal
involvement
•Newcasesofsevereformsofextra-pulmonaryTB
•Sputum smear-positive relapses
•Sputum smear-positive treatment failure cases
•Sputum smear-positive cases requiring treatment after
interruption
•New smear-negative pulmonary TB
•New less severe forms of extra-pulmonary TB

77. TB in AIDS patients in Taiwan
(1994-1997)
Disseminated TB Disseminated MAC
•No. = 22 •No. = 15
•Clinical Features •Clinical Features
Night sweats Hepatosplenomegaly
Peripheral LN Elevated SGOT,
AFB in sputum SGPT, SAP
Hilar enlargement Leukopenia
Lack of prior AIDS-defining
illness
Poor survival
Hsieh et al 1998

78. TB and HIV in Tokyo
Questionnairesurveyof48institutesforTBwithAIDS
11Japaneseand6foreignpatients
ClinicalFeatures
AdvancedHIVinfection
Middleage,feverandcough
Nonspecificchestinfiltrates
Lowlymphocytecount
Negativetuberculintest
Kanazamaetal1996

79. Differential Diagnosis of PTB
•Pneumococcalpneumonia
•Typhoidsepticemia
•Fungalpneumonia
•Pneumocystiscariniipneumonia
•Lymphocyticinterstitialpneumonia
•Kaposi’ssarcoma
•Lymphoma

81. Distribution of Tuberculosis
(1990-99)
North America
320,000
Western Europe
1,110,000
Eastern Europe
2,020,000
East Asia &
Pacific
20,460,000
South & Southeast Asia
35,140,000
North Africa &
Middle East
7,502,000
Sub-Saharan
Africa
15,012,000
Australia &
New Zealand
30,000
Latin America
& Caribbean
6,065,000
Total cases 88 million

82. Magnitude of HIV Burden
WHO region HIV
infection
Prevalence of
TB (%)
Coinfection
Africa 18.7 M 48 9 M
SEA / W Pacific 6.0 M 40 2.4 M
Americas 1.3 M 30 0.4 M
East Mediterranean 0.18 M 23 0.04 M
Europe / USA 1.35 M 11 0.15 M

83. HIV & TB -I
IMPACTOFHIVINFECTIONONTB
RiskofdevelopmentofTBinHIVinfection-
-6.9cases/100person-year(TRCChennai,2000)
IncreasingHIVprevalenceinTBclinicattendees-
-3.2%in1991to20.1%in1996(Pune)
-0.77%in1991to3.4%in1993(M.C.Chennai) 16%in1996(TRC,
Chennai)

84. HIV & TB -II
IMPACTOFTBONHIV
TBinducescytokinesviralreplication.
NegativeimpactofTBonHIVinfectioncourse.
DeathrateofpatientswithTBandHIVinfectiontwicethatofCD4
matchedcontrolswithHIVinfection.
MostdeathsduetoHIVinfectionandnotTB.

85. TB Presentation prior to diagnosis of AIDS
Coinfection
Total No.TB before AIDS
SF (Chaisson, 1987) 35 62 %
NY (Louie, 1986) 24 62 %
NY (Hand Wesger, 1987) 30 60 %
Newark (Sunderam, 1986) 29 48 %
LA (Modilevsky, 1989) 39 67 %

87. Case study
A25yearoldmanpresentswithaPUOof3monthsduration.
Onexaminationheisfebrile(102F)
Hehaslargenodesintheaxillaryandcervicalregions.Onexaminationof
theabdomenhehashepatosplenomegalyandrespiratorysystemreveals
cracklesdiffuselybilaterally.

88. © CMC, Vellore

89. What is your differential diagnosis?
Disseminatedtuberculosis
Lymphoma
Histoplasmosis
Cryptococcosis
Cytomegalovirus
Mycobacteriumaviumintracellulare

90. Pulmonary Opportunistic Infections
in HIV subjects in India
1991-94 1994-97
No. % No. %
•No. of HIV +ve 78 112
•Infections
Pulm TB 24 30.8 32 28.6
EPT 21 26.9 25 22.3
Disseminated TB 5 6.4 20 17.9
URI 16 20.5 16 14.3
Interstitial (PCP) 2 2.6 10 8.9
Non TB 24 30.8 30 26.8
Arora& Kumar 1999

91. Role of steroid therapy
Indications:
1.TBmeningitis/cerebralinvolvement
2.TBpericardialeffusion
3.TBadrenalinvolvement(replacementdosesonly)
Schedule:(formeningitis,pericarditis)
Prednisolone60mgODfor2weeksandthentaperoverfourweeks

92. Extra Pulmonary TB
Lymphadenitis Mostcommon
Disseminated Tb.Bacteraemia
Blood,bonemarrow)
Genitourinary 37%
Abnormalurinalysis
Positiveurineculture
MeningealTB 10%
Meningitis/Hydrocephalus
AbnormalCTandCSF
TBabscesses:Pancreas,spleen,breast,liver,abd.wall,psoas,mediastinal

93. Atypical Features (Extrapulmonary)
Generalizedlymphadenitis
Hepatosplenomegaly,anemia,leukopenia,pancytopenia
GenitourinaryTB
GIinvolvement–Peritoneal/intestinal
CNS–meningitis,tuberculomas
Pericarditis/myocarditis
Disseminatedinvolvement

94. Impact
IncreaseinmorbidityandmortalityduetoactivetuberculosisandHIV
infection
Increasesspreadtocontacts–horizontaltransmissionincommunity
Increasedincidenceofdrugresistantorganism
NosocomialoutbreaksofMDRtuberculosis

95. Strategies to prevent MDR
Earlydiagnosis-previoustherapyforTB
IsolationofMDRcases
Activetreatmentwithsecondlinedrugsunderdirectsupervision
Cultureanddrugsusceptibiltytesting
ProperreportingofMDRcases
Chemoprophylaxisforcontacts

96. What treatment would you start?
Anti-tuberculoustherapy
CategoryIDOTS
Duration=notlessthan6months
CotrimoxazoleDS1tabletdaily,lifelong

97. Impact of HIV in the U.S.A.
App.28000“excess”casesofTBbetween1984-1990
LargestincreaseinareaswithgreatestnumberofAIDScasesandhighest
HIVinfection
CDC1991

98. Drug resistance and HIV
CDC guidelines, MMWR, Oct 1998

99. HIV –TB Coinfection: Concerns
1.ResurgenceofTB
2.Reactivation/Re-infection
3.Augmentedeffects
4.ClinicalManifestations
5.DiagnosisandManagement-difficulties

100. Incidence
TBtransmission
Drugresistance
Mortality
Viralload
CD4count
Survival
HIV TB
Tripathi & Narain: TB 2001

101. TB Resurgence
TB–LeadingopportunisticinfectioninHIV
AIDSdefiningillness(1
st
indicationofimmunedeficiency)
Coinfection:About38%(15of40million,globally)
RiskofTB7-10%peryear(Almost100%lifetimerisk)
TBinHIV(100timespopulationincidence)

102. Endogenous reactivation
HIVisthemostpotentriskfactorforreactivationoflatenttuberculosis
HIVnegativerate<1%peryear
(10%lifetime)
HIVpositiverate~7-10%peryear
(apprx100%lifetime)
IncidenceofTBis100timesinHIVthaningeneralpopulation

103. Exogenous infection
PatientwithHIVinfectiondevelopsinfectionwithMycoTuberculosis~
40%developactivediseasewithinweeksandprogressesrapidly.
Associatedwithincreasedmorbidityandmortality
despiteoptimaltreatment
Spreadthediseaserapidlyamongcontactsandhealthcareworkersleading
tonosocomialoutbreaks

104. Evidence: exogenous infection
HIVpatientswithlowCD4countsarelikelytovisithospitalswhereTB
transmissionislikely
UsuallyhavepatternofLZoneinfiltrates,adenopathy,pleuraleffusion
suggestiveofrecentinfection
RFLPanalysishasconfirmed40%ofsuchpatientshaveidenticalstrainof
MTBsuggestingclusteringofcontacts

106. HIV related TB-clinical features
HIV negative Early HIV Advanced HIV
Chest
X-ray
U. lobe-50%
Cavities-50%
Mixed Adenopathy
Effusion
Lower lobe
Miliary
Sites Pulm-80%
Extrapulm-16%
Both-4%
Intermediate Pulm-30%
Extrapulm-30%
Both-30%
Sputum
+
70% 50% 30%

110. Molecular diagnosis-RFLP

111. BacteriophageAssay
Utilizesspecificmycobacteriophagetoidentifypresenceofviablet.b.in
sputum
Virucidalsolutionaddedtokillfreephages
Bacilliinfectedwithphageamplifiedbyaddingnonpathogenicmycobacteria
Colonyofphagesvisualizedasplaquesonlawnofmycobacteria
Drugsusceptibilityresultspossiblein48hrs

112. Initiating ART in HIV infection