Managing Opportunistic Infection: Focus on TB-HIV

Rudi Wisaksana Departement of Internal Medicine

Hasan Sadikin Hospital HIV Working Group, Padjadjaran University

Getting To Zero

• Zero new infection – Sexual transmission reduced by half – Vertical transmission eliminated – IDU have access to preventive measures

• Zero AIDS-related death – Universal access to ART for PLHIV who eligible – TB related death reduced by half

• Zero discrimination – Countries with punitive laws reduced by half – HIV related travel restriction eliminated in half of countries – HIV-women specific need addressed in half of nations – Zero tolerance for gender-based violence

TB-HIV

• HIV and TB: strongly associated – HIV: 25% of deaths due to TB

– TB: 33% of deaths due to HIV

• Indonesia: – 3rd largest HIV cases in Asia

– 5th largest TB case in world

• Bandung: – HIV patients 30% treated for TB

– TB inpatients 10% HIV infected

Factors associated with mortality

Died during follow-up (n=124)

Still alive (n=1221)

Age 30 (26-34) 29 (26-32)

Male 72.6% 63.6%

History IDU 46.8% 47.9%

Oral candida at baseline

55.6% 31.6%

Haemoglobin at baseline

10.4 (9.1-12.1) 12.4 (10.8-14.0)

CD4 at baseline 15 (6-43) 85 (19-304)

Previous TB treatment

41.9% 24.7%

TB treatment during follow-up

28.2% 15.9%

Whaltman, 2012

TB

No TB

TB-HIV management

RSHS: Performance indicators

Indicator Achievement Target

TB patient offer for HIV test

2,2% 15%

TB – HIV patient on ARV

84% 60%

TB – HIV patient on CPT

81% 80%

Indicator Achievement Target

HIV patient screening for TB

77,9% 80%

TB – HIV patient on TB treatment

88% 80%

INH prophylaxis Therapy Piloting NA

HIV positif pada penderita TB ?

• WHO 2009: – Indonesia TB HIV: 2.8%

• Kohort TB di Bandung – ~1000 patients

– HIV + 1%

• RS Hasan Sadikin: 2008 – TB dirawat : 14%

– TB extraparu : 25%

HIV in Extra Pulmonary TB

Early Death in TBM Patients

0 10 20 300

50

100HIV-positive

HIV-negative

days

Perc

en

t su

rviv

al

Ganiem, 2009

Adult N=185

Male 60%

Median age 30 yo

HIV (+) 25%

Median CD4 13 cells/ml

200

Typical Tuberculosis

Atypical PTB

EPTB

Diagnosis TB ?

50

500

HIV awal

HIV lanjut

CD4

Diagnosing TB

• Common Procedure

– Sputum microscopy

– Chest radiography if sputum negative

– Culture

• Con’s

– Time consuming

– Multiple journey

– Insensitive

TB diagnosis affected by CD4

Whaltman, 2012

Microscopic Observed Drug Sensitivity (MODS)

Positivity of Ziehl

Neelsen

23% (39/167)

Positivity of MODS

34% (56/167)

Positivity of Ogawa

31% (51/167)

Days

Perc

en

t o

f p

osit

ivit

y

0 20 40 600

20

40

60

80

100OGAWA

MODS

MODS VS OGAWA

Chaidir, 2011

Auramin compare to culture (n=404)

Test Parameter ZN (CI 95%) FM (CI 95%)

Sensitivity 57 (43 -71) 84 (73 - 94)

Specificity 97 (82-110) 85 (75 - 95)

PPV 70 (57 - 83) 44 (30 - 57)

NPV 94 (88 - 100) 97 (93 - 100)

LR (+) 16.90 5.60

LR (-) 0.44 0.19 Sequencing: FM then ZN?

Tina, 2010

0

10

20

30

40

50

60

70

80

90

TW3 TW4 TW1 TW2 TW3 TW4

Number of new HIV pts

Number of TB suspects

Number of sputum examination

Number of smear pos

Number of HIV pts with TBtreatment

Source: TB Register in HIV clinic - 2012

2011 2012

X-pert

Xpert MTB/RIF assay for diagnosis TB

LAM

• Urine lipoarabinomannan (LAM)

• Cell wall components of MTB

• Cost $3.50/strip in 30 minutes

• Sensitifity: 95%

• More sensitive in CD4

< 50 cells/ml

Pengobatan TB-HIV

TB Treatment

• Generally same as non HIV

• Duration:

– 6 months for majority

– 9 – 12 months for patients with delayed responses, cavitary, EPTB, CNS TB

• Intermittent dosing in continuation phase

– Preferable to complete treatment

– Twice weekly : higher risk of relaps

Starting ART in TB

• Clinical and survival benefit of starting ART within the first 2 weeks treatment for an acute OI, excluding TB (Zolopa A, et al. ACTG A5164)

• Initiating ART 2 weeks after the start of tuberculosis treatment significantly improved survival (Camelia, Sapit, Stride) Except for meningitis TB (Torok ME, et al)

TB IRIS

• Diagnosis of HIV and TB – WHO criteria • Response to TB treatment – improved/stabilised • On ART

– Response documented by >1 log decrease in HIV RNA, though seldom available

• Onset within 3 months (up to 6) of starting/changing ART • Exclusion of alternative explanation

TB treatment failure due to drug resistance Another opportunistic infection or neoplasm Drug toxicity or reaction Complete non-adherence to ART

Work-up Pathway

Intercurrent opportunistic or inflammatory disease

Before HAART Weeks to months after

HAART > 1 year in HAART

ART failure (Immunological or virological failure)

ART failure (Immunological or virological failure)

Yes No No

No IRIS (typical OI) IRIS should be

assumed (especially in ‘‘atypical”

manifestation)

IRIS generally not assumed (especially

in ‘‘atypical” manifestation)

Reason for failure (Adherence, Resistance?)

Stoll M et al.: Curr Infect Report 266-76, 2003

TB-HIV patients

registered in HIV clinic

56 TB-HIV 25

TB-HIV patients

registered in

DOTS clinic

7

Need Good TB-HIV Collaboration

RSHS TB register 2012

Isoniazide Prophylactic Therapy (IPT)

• Dianjurkan WHO

– Reduksi risiko TB: 33-64%

– Terutama untuk TST (+)

• OAT: INH, Rif,

• Durasi: ? 6 – 36 bulan, tergantung tingkat transmisi TB

• Hambatan:

– Kesulitan menyingkirkan TB aktif pada CD4 rendah

ARV as TB prevention

• ARV strongly associated with reduce TB incidence

• Combined ARV and IPT superior than ARV or IPT alone

Suthar, 2012

Pelaksanaan IPT di RSHS

HIV (+)

Belum ARV

TB aktif No TB aktif

IPT

Terapi TB* (OAT)

Terapi TB* (OAT)

Sudah ARV > 3 bln

No TB aktif TB aktif

Belum indikasi ARV

Indikasi ARV

Skrining TB * Skrining TB *

Selesai terapi TB Selesai terapi TB

Teratai, 2012

TB latent: TST vs IGRA

Tuberculin Skin Test

IGRA (+) IGRA (-)

>10 mm 16 7

< 10 mm 8 48

> 5 mm 18 8

< 5 mm 6 47

IGRA:Overall prevalence: 25.5%

Meijerink, 2012-13

Conclusion

• TBHIV collaboration is essential

• Early Finding

• Diagnosis:

– Difficult, need new tools

• Treatment:

– TB treatment same as non HIV

– ART: 2 weeks after TB treatment

• Prevention: IPT and early ART