TB - HIV

Co-infection

Darmanto, MD, M.Kes

Internist
 Global summary of the AIDS epidemic  2014

Number of people Total 36.9 million [34.3 million – 41.4 million]

living with HIV Adults 34.3 million [31.8 million – 38.5 million]
Women 17.4 million [16.1 million – 20.0 million]
Children (<15 y) 2.6 million [2.4 million – 2.8 million]

People newly Total 2.0 million [1.9 million – 2.2 million]

infected Adults 1.8 million [1.7 million – 2.0 million]
with HIV in 2014 Children (<15 y) 220 000 [190 000 – 260 000]

AIDS deaths in Total 1.2 million [980 000 – 1.6 million]

2014 Adults 1.0 million [760 000 – 1.8 million]
Children (<15 y) 150 000 [140 000 – 170 000]
Adults and children estimated to be living with HIV  2014

Eastern Europe
North America and Western and Central Europe & Central Asia
2.4 million 1.5 million
[1.5 million – 3.5 million] [1.3 million – 1.8 million]
Middle East & North Africa
Caribbean 240 000
280 000 [150 000 – 320 000]
[210 000 – 340 000] Asia and the Pacific
Latin America
1.7 million
Sub-Saharan Africa
25.8 million
[24.0 million – 28.7 million]
5.0 million
[1.4 million – 2.0 million] [4.5 million – 5.6
million]

Total: 36.9 million [34.3 million – 41.4 million]

Indonesia 2005 - 2014

600,000
400,000
200,000

Total: 640,000 (2014)

 Estimasi kasus baru TB (x 1000)

0
500
1000
1500
2000

India

China

Indonesia

Bangladesh

Nigeria

Pakistan

Philippines

South Africa

Russian Federation

Ethiopia

DR Congo

Viet Nam

Kenya

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UR Tanzania

Brazil

Thailand

Myanmar

Zimbabwe

Uganda

Cambodia

Afghanistan

Mozambique
22 negara yg terbeban: 80% dari semua kasus baru
 Leading Causes of Mortality from
Infectious Diseases, 2001

Respiratory infections 3.9*

AIDS 2.9
Diarrheal diseases 1.9
Tuberculosis 1.6
Malaria 1.1

*in millions

Source: WHO/CDS/2003.15
TB/HIV

Two Diseases

One Patient
TB – HIV : Global Emergencies

 Diperkirakan
1/3
penduduk dunia  HIV
TB
HIV & TB
 60– 80 % TB 
Terinfeksi HIV TB
 Estimasi prevalensi koinfeksi TB-HIV, 2000

Rate per 100 000

<5
5 - 9.9
10 - 99
100 - 999
1000 - 4999
> 5000
Tdk ada estimasi

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Source: Corbett EL, Watt CJ, Walker N, Maher D, Raviglione MC, Williams B, Dye C. (submitted for publication).
Infeksi TB vs Penyakit TB (TB aktif)

 Infeksi TB –tidak dapat menginfeksi orang

lain
 Penyakit TB –menularkan
 10% infeksi TB  penyakit TB
 TB aktif menular  10-15 orang/tahun

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Kapan infeksi TB menjadi penyakit?

 dalam 2 tahun pertama setelah infeksi

 Jika orang menjadi immunocompromised
 HIV
 Kanker
 Khemoterapi
 Diabetes yang tidak terkontrol
 Malnutrisi

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Natural History of Tuberculosis Infection
Interaksi TB-HIV
 HIV merupakan faktor risiko utama
menyebabkan TB aktif
 Jumlah progresi menjadi TB aktif:
 > 40 % pada pasien dengan HIV
 5 % pada pasien tanpa HIV
 Risiko reaktifasi infeksi TB:
 2.5-15 % setiap tahun pada pasien dgn HIV
 < 0.1 % setiap tahun pada pasien tanpa HIV

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 Interaksi TB-HIV
Kerentanan
Presentasi

HIV TB

Progresi Penyakit
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 Natural History of HIV Infection

1200
Primary
infection Possible acute HIV syndrome Death
1100
Cells/mm 3

Wide dissemination of virus

1000 Seeding of lymphoid organs
Opportunistic
900 diseases 1:512

800 Clinical latency 1:256

)

Plasma Viremia Titer

700 1:128
T

Constitutional
600 1:64
CD4

symptoms

)
(

500 1:32

400 1:16

(
300 1.8

200 1.4

100 1.2

0 0
0 3 6 9 12 1 2 3 4 5 6 7 8 9 10 11
Weeks Years
 Natural History of Untreated HIV Infection

1000
800
600
400
200
CD4 + 0 Early Opportunistic Infections
Cells Late Opportunistic Inf.

1 2 3 4 5 6 7 8 9 10 11 12 13 14

Infection Time in Years

Perjalanan dan manifestasi klinis yang lazim

1000 TB
900 TB
800
700 TB
600 TB
500 HZV
400
CD4 300 OHL
Oral candida
COUNT PCP TB
TB
200 Cryptococcal meningitis
100 Cryptosporidial diarrhea PPE
50 CMV
<50 MAC TBTB
0
0369 1 2 3 4 5 6 7 8 9 10
Months Years
 4.0
Relative life time risk of

3.0
tuberculosis

2.0

1.0
0 200 400 600 800
CD4+/uL 4/01/201
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 Efek jumlah CD4 terhadap risiko TB
di antara ODHA
Insidens TB (per 100 /thn)
20
>350 200-350 <200

15

10

0
Italia AS Afrika Selatan
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Antonucci JAMA 1995;274:143; Markowitz Ann Int Med 1997;126:123; Badri Lancet 2002;359:2059
 TB dan AIDS
Risiko TB
70% selama hidup 60%
60%
50%
40%
30%
20% 10%
10%
0%
PPD+/HIV-negatif PPD+/HIV+
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Masalah
stigma

perawatan
jangka panjang

HIV TB
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 Fighting TB and HIV

“We cannot win the battle against

AIDS if we do not also fight TB. TB
is too often a death sentence for
people with AIDS ”.

Nelson Mandela

Nelson Mandela at 2004 International AIDS Conference

(http://news.bbc.co.uk/1/hi/world/asia-Pacific/3895525.stm)
 Standard TB Symptom
Screening Tool
• Batuk – baru terjadi atau sudah
berlangsung lama

• Penurunan BB– dalam 1 bulan

• Keringat malam hari

• panas
Getahun H et al. PLoS Medicine 2011, 8: e1000391
 Pemeriksaan

Sputum BTA dan Rontgen

Time consuming – Costly - Tests are insensitive

New TB diagnostic tools: Xpert MTB/Rif

Sputum
Specime
n
Other
Specime
n

Sensitivities: Diagnosis in
Smear-positive PTB - 1 specimen = 98% under 2 hours
Smear-negative PTB - 1 specimen = 72%; 3 specimens
= 90%
EPTB - different specimens = 81% (range 25% - 97%)
Boehme et al, N Engl J Med 2010; 363: 1005-15: Lawn and Zumla, Exp Rev Anti-Infect
Ther 2012
New TB diagnostic tools: Urine TB-LAM
Urine LAM

URINE
SPECIMEN

TB-LAM Dip-stick

Determine TB-LAM test strips (diagnosis in 30 minutes)

[specificity 98%: sensitivity increases as CD4 count declines (~66% at CD4 < 100
cells/uL]
Lawn et al, Lancet Infect Dis 2011; Dorman et al, CROI
2012
 “Three I’s” in HIV care settings

“TB diagnosis”

Isoniazid Preventive Therapy (IPT)

Intensified case
finding (ICF)

Infection Control (IC)

 Diagnosis TB Paru
Batuk 3 minggu
Jika 1 positif,
BTA X 3 Jika 2/3 positif:
X-foto dan OAT
evaluasi
Jika negatif:
Antibiotika spektrum lebar 10-14 hari
Jika gejala tetap, ulangi smear BTA, X-foto

Jika konsisten dengan TB

Obat Anti-TB4/01/201
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 Manifestasi Klinis TB pada HIV

Dini Lanjut

 Klinis Tipikal Atipikal

 PPD Biasanya (+) Biasanya (-)
 Foto dada Tipikal Atipikal
 Gamb Paru Lobus Atas Lob. bawah/tengah
 TB ekstra paru Jarang Sering/banyak
 Mikobakteremi Tidak ada Ada
 Adenopati hilus/ Tidak ada Ada
mediastinum
 Efusi pleura Jarang Sering
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 TB paru
Presentasi tergantung kpd stadium
HIV
HIV awal HIV lanjut
(stad 1-2) (stad 3-4)

Klinis Haemoptysis High fever

Batuk kronis Sesak napas
Keringat malam BB ↓
BB ↓

Hapusan Sering positif Sering negatif

(80-90%)

X-ray Kavitas TB Primer:

Lobus atas Lobus bawah
infiltrat infiltrat
KGB intra-torakal >
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Hasil X-foto dada pasien TB
dengan infeksi HIV

HIV lanjut
HIV awal (severe immuno-compromise)
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Infiltrat interstitial

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Limfadenopati hilar

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 Perbandingan gambaran klinis TB pada
penderita terinfeksi HIV dan tidak terinfeksi HIV
Gambaran HIV (+) HIV (-)
Keluhan respirasi +++ +++
Penyakit ekstra paru +++ +
Kavitas + +++
Foto toraks atipikal +++ +
PPD neg ++ +
Efek samping obat ++ +
Angka mortalitas +++ +
Relaps ++
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Definisi AIDS pada orang dewasa menurut WHO dimana fasilitas
laboratorium tidak tersedia
Kriteria AIDS terpenuhi apabila ada sedikitnya 2 mayor sign dan sekirang-kurangnya 1
minor sign.
Mayor sign :
• Penurunan berat badan > 10% dari berat badan
• Diare kronis lebih dari satu bulan
• Demam lama lebih dari satu bulan
Minor sign :
• Batuk lama lebih dari satu bulan
• Pruritus dermatitis generalisata
• Riwayat Herpes Zoster
• Kandidiasis orofaring
• Herpas simplek kronis
• Limfadenopatia generalisata
 Stadium penyakit, secara klinik berdasarkan gejala klinik dan
jumlah sel limfosit CD4 (US-CDC 1993 revised criteria)

JumlahCD4 SEL/MM3 Kategori klinik

A B C
> 500 1 A1 B1 C1
200– 499 2 A2 B2 C2
< 200 3 A3 B3 C3

STADIUM 1: A1, A2, B1, STADIUM 2: B2, A3, B3,

STADIUM 3: C1-C3

A = Asimtomatik, C = gejala penunjuk AIDS, B = gejala bukan A/C

 Presumptive or diagnosed TB

Provider initiated HIV testing and

counselling [PITC]

If HIV- seropositive

Start cotrimoxazole preventive therapy as soon as

possible [25% - 46% mortality reduction]

Start antiretroviral therapy as soon as

possible [64% - 95% mortality reduction]
 WHO 2010 ART Guidelines

All HIV-positive TB patients

eligible for ART, regardless of
CD4 count

ART initiated as soon as

possible after the start of TB
treatment
Early versus Standard ART in HIV-infected adults in Haiti
[Severe P et al, NEJM 2010; 362: 257-265]

(Early = CD4 200-350; Standard= CD4<200 or AIDS

50% reduction in TB incidence 75% mortality reduction

Early ART (CD4 350-500)
versus
Delayed ART (CD4 < 250)

• 96% reduced HIV

transmission to HIV-negative
partner

• 40% reduction in clinical

events in HIV-infected
persons – mainly related to
EPTB (3 cases with early
ART versus 17 with delayed
ART)
 Tabel 6: Daftar Obat Antiviral (ARV)

Obat antiretroviral terbagi atas dua klas utama yaitu :

1) Reverse trantriptase inhibitors (RTIs):
a) Nucleoside reverse trantriptase inhibitors (NsRTIs)
- Zidovudine (AZT, ZDV) - Didadosine (ddl)
- Stavudine (d4T) - Lamivudne (3TC)
- Abacavir (ABC) - Zalzitabine (ddC)
b) Non-nucleoside reverse trantriptase inhibitors (NNRTIs)
- Nevirapine (NVP)
- Evavirens (EFV)
- Delavirdine (DLV)
c) Nucleotide reverse trantriptase inhibitors (NtRTIs)
- Tenonovir
2) Protease inhibitors (PIs)
- Saquinavir (SQV) - Ritonavir (RTV)
- Indinavir (IDV) - Nelvinavir (NFV)
- Amprenavir (AVP)
 Regimen Obat Antiviral (ARV) pd orang dewasa

Kombinasi regimen tanpa PIs:

• 2 NsRTIs (zidovudine, lamivudine) + 1 NNRTI (nevirapine
atau evavires)
• 3 NsRTI : (zidovudine/lamivudine/abacavir)
• Alternative kombinasi NsRTI :
• Zidovudine + didadosine
• Stavudine + lamivudine atau didadosine

Kombinasi regimen mengandung PIs :

• 2 NsRTI + 1 PIs : zidovudine, lamivudne, indinavir
Early versus Standard ART in HIV-infected adults in Haiti
[Severe P et al, NEJM 2010; 362: 257-265]

(Early = CD4 200-350; Standard= CD4<200 or AIDS

50% reduction in TB incidence 75% mortality reduction

Early ART (CD4 350-500)
versus
Delayed ART (CD4 < 250)

• 96% reduced HIV

transmission to HIV-negative
partner

• 40% reduction in clinical

events in HIV-infected
persons – mainly related to
EPTB (3 cases with early
ART versus 17 with delayed
ART)
WHO Guidance for IPT:
•PLHIV with unknown or
positive TST and who do not
have TB should receive IPT

•TST not a requirement for

starting IPT

•IPT for 6 months

(strong recommendation)

•IPT for 36 months

(conditional recommendation)
 Efek samping
 HAART  Terapi TB
- demam - demam
- ruam kulit - ruam kulit
- gangguan hati - gangguan hati
- neuropati - neuropati

Sering terjadi dan sama

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