MANAGEMENT OF

OPPORTUNISTIC INFECTION

Tuti Parwati Merati Division of Tropical and Infectious Diseases,

Department of Internal Medicine Faculty of Medicine,

Udayana University, Bali

Pendahuluan

• Penanganan HIV/AIDS:

– Mengobati IO,

– Pengobatan dengan ARV,

– Pengobatan suportif : fisik/psikologis

• Prinsip : IO di obati terlebih dulu, lalu ART

OIs and CD4 in HIV Infection

1000

900

800

700

600

500

400

300

200

100

50

<50

0

PCP Cryptococcal meningitis

PPE

CD4

COUNT

0 3 6 9 1 2 3 4 5 6 7 8 9 10

Months Years

TB

Oral candida OHL

HZV

CMV

MAC

TB

TB

TB

Cryptosporidial diarrhea

12/04

Mucocutaneous Candidiasis: Clinical Manifestations

Erythematous candidiasis

Credit: D. Greenspan, DSC, BDS, HIV InSite

Pseudomembranous candidiasis

Credit: Pediatric AIDS Pictoral Atlas, Baylor International Pediatric AIDS Initiative

12/04

Mucocutaneous Candidiasis: Clinical Manifestations

Esophageal candidiasis

Credit: P. Volberding, MD, UCSF Center for HIV Information Image Library

12/04

Mucocutaneous Candidiasis: Diagnosis

• Oropharyngeal:

– Usually clinical diagnosis

– KOH preparation, culture

• Esophageal:

– Clinical, with trial of therapy

– Endoscopy with histopathology and culture

• Vulvovaginal:

– Clinical diagnosis, KOH preparation

12/04

Mucocutaneous Candidiasis: Treatment

Oropharyngeal • Preferred (7-14 days):

– Fluconazole 100 mg PO QD – Itraconazole oral solution 200 mg PO QD – Clotrimazole troches 10 mg PO 5 times daily – Nystatin suspension 4-6 mL QID or 1-2 flavored pastilles 4-5

times daily

• If refractory to fluconazole: – Itraconazole oral solution ≥200 mg PO QD – Amphotericin B suspension 100 mg/mL, 1 mL PO QID (not

available in United States) – Amphotericin B 0.3 mg/kg IV QD

12/04

Mucocutaneous Candidiasis: Treatment

Esophageal

• Systemic therapy required

• Preferred (14-21 days):

– Fluconazole 100 mg (up to 400 mg) PO or IV QD

– Itraconazole oral solution 200 mg PO QD*

– Voriconazole 200 mg PO BID*

– Caspofungin 50 mg IV QD

*May have significant drug interactions with certain antiretroviral medications; consult information on drug interactions before coadministering with antiretrovirals.

12/04

Mucocutaneous Candidiasis: Treatment

Esophageal

• If refractory to fluconazole:

– Caspofungin 50 mg IV QD

– Voriconazole 200 mg PO or IV BID*

– Amphotericin B 0.3-0.7 mg/kg IV QD

– Amphotericin liposomal or lipid complex 3-5 mg/kg IV QD

*May have significant drug interactions with certain antiretroviral medications; consult information on drug interactions before coadministering with antiretrovirals.

200 CD4

Typical Tuberculosis

Atypical Pulmonary TB

Extra Pulmonary TB

TB manifestation regarding of CD4 levels

50 CD4

500 CD4

HIV early

stage

Advance and

severe HIV Dis.

Clinical Manifestation of TB- HIV

High CD4 Low CD4

• Clinical finding Tipical Atipical

• PPD (+) commonly (-)

• Rontgen Tipical Atipical

• Rontgen Superior lobe Inf/lower lobe

• Extra pulm TB UnCommon Common

• Hilar adenopati Neg Pos

mediastinum

• Pleural effusion Uncommon common

TB DIAGNOSIS

• History of ilness (anamnesis)

• Physical finding

• Microbiologic examination

• Rontgen

• Tuberculin test

• Suspicion

Diagnostic

• Laboratoris – AFB, 3x

– Cultures

• Negative AFB result not exclude TB dx

• Culture positive rate : – 20 -40% HIV-TB co-infection

Symptoms and sign of Active TB

• Prolonged cough

• Chest pain

• Hemoptysis

• Fever

• Shivering

Night sweating

Fatigue

Loss of apetite

Loss of BW

Clinical manifestation of TB

In HIV+ and HIV -

Sign/symptoms HIV (+) HIV (-)

Respiratory symptoms +++ +++

Extra Lung Diseases +++ +

Cavity + +++

Atypical Chest X ray +++ +

PPD neg ++ +

Drugs Side Effect ++ +

Mortality +++ +

Relaps ++ +

Study Methods

A retrospective study of HIV-TB co-infection

patient’s medical record at VCT clinic on

Sanglah General Hospital during January

2005 to Maret 2011

Results of HIV-TB Coinfection

Results of HIV-TB coinfection

Results of HIV-TB Coinfection

Terapi ARV pada Dual HIV-TB

Kondisi Waktu Pemberian

CD4 < 200 Mulai terapi TB.

ARV segera setelah toleransi (2 mgg-2 bl)

CD4 200-350 Mulai terapi TB.

ARV setelah terapi vs ARV setelah toleransi

CD4 > 350 Mulai terapi TB, setelah selesai:

VL > 55.000 ARV

VL < 55.000 tunda ARV, monitor CD4

Tidak tersedia

pemeriksaan

CD4

Mulai terapi TB.

ARV diberikan berdasarkan gejala klinis adanya

def. imun

WHO, 2003

Pengobatan TB pada odha

• Pengobatan untuk infeksi TB pada odha diberikan empat jenis OAT selama 6- 9 – 12 bl (rifampicin, isoniazid, pyrazinamide,ethambutol)

• Berikan steroids pada meningitis & pericarditis

• Pengobatan menjadi tidak sederhana, karena adanya co infeksi oleh virus hepatitis B, hepatitis C, anemia, pemakaian obat antiretrovirus (ARV), dan keluhan saluran cerna.

EVALUASI TERAPI

• BAIK TERHADAP GEJALA HIV MAUPUN M.TB

– EVALUASI KLINIS

– EVALUASI LABORATORIS

– EVALUASI RONTGENOLOGIS

– EFEK SAMPING OBAT (ARV/OAT)

– INTERAKSI OBAT

– RESISTENSI OBAT

– ADHERENCE THD ARV DAN OAT

Masalah terapi: • Adherence / jumlah pil banyak

• Efek toksisitas yang tumpang tindih – mual, muntah, ruam kulit, hepatitis, anemi

• Interaksi obat – Rifampisin merupakan enzyme inducer yang kuat

• ‘Paradoxical worsening’ TB – Reaksi Immune reconstitution

– Sering terjadi jika ART dimulai lebih dini pada OAT

– Jika mungkin tunda ART sampai fase intensif selesai

Terapi ko-infeksi TB-HIV

Pneumocystis jiroveccii

Signs:

• fever

• respiratory rate

• chest often clear to auscultation

Diagnosis:

• CXR:

– bilateral peri-hilar shadowing

– 10% normal,

• induced sputum/BAL: silver methanamine stain

PCP Pneumonia bakterial

PCP (Pneumocystis jiroveccii)

CD4+ < 200 (mean 110) Less common in Indonesia than in USA or Australia Sites: • Pulmonary (most common) Presentation: insidious, often over 3-4 weeks • fever >39oC • dry cough, rarely productive (if purulent sputum – think of

another diagnosis) • increasing dyspnoea – may be subtle in exercise

tolerance in early stages – take a careful history! • Usually with other features of HIV: wasting, oral thrush

12/04

PCP: Histopathology)

Lung biopsy using silver stain to demonstrate P jiroveci organisms in tissue.

Credit: A. Ammann, MD, UCSF Center for HIV Information Image Library

Treatment of Pneumocystis jiroveccii

Often empirical

• iv/oral cotrimoxazole

– 20 mg/kg/d of trimethoprim plus sulfamethoxaxole 100mg/kg/d) for 3/52

• + high dose steroids if pO2 < 70mmHg

Alternatives:

• iv pentamidine 4mg/kg/d

• dapsone 100mg /d plus trimethoprim 20mg/kg/d

• clindamycin 600mg qid + primaquine 15-30mg/d

Prophylaxis of Pneumocystis jiroveccii

Primary / secondary

CD4 < 200/ul or < 20%

TMP/SMZ, drug of choice

Fansidar (pyrimethamine sulfadoxine),

1 tab/week

Dapsone 50 – 100 mg/D

Stop prophylaxis : CD>200 (3 mos)

TERIMA KASIH

MATUR SUKSMA

THANK YOU