HIV: Infeksi Oportunistik dan Ko-Infeksi
Lecture SeriesPaham dan Peduli HIV/AIDS
Jumat, 3 Mei 2019Kampus Unika Atmajaya Semanggi
ProfilDr.med. Abraham Simatupang, dr., MKesClinical Clinical PharmacologistPharmacologistFakultas KedokteranUniversitas Kristen Indonesia (UKI)
oDokter – FK UKI (1986)oMKes. – FK UGM (1993)oDoktor Medizine – University of Bonn (1996)
•Direktur – Akademi Fisioterapi (2009-2014)• Direktur Pokja HIV & AIDS (2007-2009)• Kepala Dept. Farmakologi & Terapi (2004-2016)• Direktur Lembaga Penelitian (1998-2004)•Pendiri German-Indonesia Medical Association (DIGM)/Asosiasi Dokter Jerman Indonesia• Pendiri Indostaff (Univ. Staff Development)• Pendiri dan Ketua Rumah Philia (pelayanan Ibu & Anak dengan HIV/AIDS. “Melayani bukan dilayani”
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Learning ObjectivesAt the end of this module, you will be able to:• Describe the difference between HIV infection
and AIDS• Describe the pathogenesis of some opportunistic
infections (OI) e.g. HBV, HCV, Toxoplasmosis, TB, Chronic Diarrhea, CMV, etc
• Describe the prevention and some general approaches to OI
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Content Overview• What is HIV?• What is AIDS?• What is the difference between OI and
Infections
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What is HIV?
• Human: Infecting human beings
• Immunodeficiency: Decrease or weakness in the body’s ability to fight off infections and illnesses
• Virus: A pathogen having the ability to replicate only inside a living cell
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Types of HIV Virus• HIV 1
§ Most common in sub-Saharan Africa and throughout the world
§ Groups M, N, and O§ Pandemic dominated by Group M
§ Group M comprised of subtypes A - J
• HIV 2§ Most often found in West Central Africa, parts
of Europe and India
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Replikasi Virus
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• Enzim Virus: • Reverse Transcriptase: RNA → DNA• Protease: cuts long protein strands into small
functional proteins and enzymes needed to assemble mature virus
• Integrase: integrasi HIV DNA ke dalam DNA sel inang (host)
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What is AIDS?• Acquired: To come into possession of
something new • Immune Deficiency: Decrease or weakness in
the body’s ability to fight off infections and illnesses
• Syndrome: A group of signs and symptoms that occur together and characterize a particular abnormality
AIDS is the final stage of the disease caused by infection with a type of virus called HIV.
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HIV vs. AIDS• HIV is the virus that causes AIDS• Not everyone who is infected with HIV has
AIDS• Everyone with AIDS is infected with HIV• AIDS is result of the progression of HIV
Infection• Anyone infected with HIV, although
healthy, can still transmit the virus to another person
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Basic Terms• Antigen: A substance which is
recognized as foreign by the immune system. Antigens can be part of an organism or virus, e.g., envelope, core (p24) and triggers antibody production.
• Antibody: A protein (immunoglobulin) made by the body’s immune system to recognize and attack foreign substances
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Testing for Viral Infection and Immune Response • Viral infection
§ Viral Load§ p24 Antigen
• Immune response§ Antibody (IgG, IgM)§ Cellular response (CD4)
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Window Period (Periode jendela)• Time from initial infection with HIV until
antibodies are detected by a single test• Usually 3-8 weeks before antibodies are
detected• May test false-negative for HIV antibodies
during this time period• Can still pass the virus to others during
this period
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Disease Progression• Severity of illness is determined by amount
of virus in the body (increasing viral load) and the degree of immune suppression (decreasing CD4+ counts)
• As the CD4 count declines, the immune function decreases.
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WHO HIV/AIDS Classification SystemStage I
Asymptomatic
Stage IIMinor
Symptoms
Stage IIIModerate
Symptoms
Stage IV
AIDS
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Gejela-gejala utama AIDS
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Mulut: KandidaEnsefalitis, Meningitis, Toksoplasmosis
Paru2: TB, Pneumosistis pneumonia
Kulit: Tumor Sarkoma Kaposi
Pencernaan: Esofagitis, Diare kronis, Tumor
Berat Badan turun drastis,Fatigue
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Toxoplasmosis• Penyebab: Toxoplasma gondii (protozoa)• Paling sering toxoplasma encephalitis• Biasanya CD4 < 200 sel/mm3 (risiko
meningkat bila CD4 < 50 sel/mm3• Profilaksis: TMP-SMX (double strength:
160 mg TMP-800 mg SMX) 2 x/hari selama 14 hari
• Infeksi akut: Pirimetamine-Sulfadiazine
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Kandidiasis• Infeksi jamur tersering pada
ODHA• Bisa bertambah berat sampai
ke daerah kerongkongan (esofagus) → kesulitan makan dan minum§ Cotrimoxazole: 10 mg troches 4-5
times/day for 2 weeks (B II)§ Nystatin suspension: 4-6 mL
(400,000-600,000 units/mL) 4 times/day
§ Amphotericin B suspension: (100 mg/mL) 1 mL 4 times/day
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Pneumonia - Pneumocystis jiroveci (carinii)• Organisme di
dapatkan di seluruh dunia
• Antibodi pada 80% anak normal umur 4 tahun
• Bisa dicegah dengan profilaksis TMP-SMX
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INTERACTION OF TB & HIV• HIV -↑number of TB cases and alters the
clinical course of TB disease.• As HIV infection progresses → CD4+ T-
lymphocytes decline in number and function.
• Thus, the immune system becomes less able to prevent the growth and local spread of M. tuberculosis
• The most common types of TB in HIV are disseminated and extra pulmonary TB
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Skrining TB aktifAlat skrining: TB ücough of any durationü fever of any durationüexcessive night sweatsü loss of weight >3kg/1moüTempat: klinik,VCT,PMTCT, Puskesmas,
dll/.ü Cough registers
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Kolaborasi TB-HIV• Semua pasien HIV → skrining TB• Anamnesis: Batuk lama, keringat malam, BB
Turun• Positif? → Rontgen Toraks, Sputum BTA• Rawat ruang isolasi TB• Semua pasien TB → skrining HIV• Positif?• Terapi ARV tanpa tunggu hasil CD4• Terapi TB dimulai dulu 2 minggu→ + ARV
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ISONIAZID PREVENTIVE THERAPY(IPT)ü Tab 300mg OD INH selama 6 bulan.ü Diulang setiap 2 tahunü Eligibility: - Tidak ada hepatitis- Tidak mendapatkan terapi TB dalam 2 tahun terakhir- Tingkat kepatuhan tinggi/adherence- Tidak ada penyalahgunaan alkohol- Tidak ada obat kontraindikasi dengan INH- Tidak ada tanda neuritis perifer
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Major Hepatitis VirusesVirus Means of transmission
Hepatitis A Fecal-oral: Contaminated food or water
Hepatitis B Sexual, mother-to-child, blood exposure (transfusion, IDU, tattoo)
Hepatitis C Blood exposure (transfusion, IDU, tattoo); sexual, mother-to-child less common
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HBsAg Prevalence³8% - High
2-7% - Intermediate <2% - Low
Geographic Distribution of Chronic HBV Infection
CDC
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• Sexual
• Parenteral
• Perinatal
HBV Modes of Transmission
CDC
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• Sexual
• Parenteral
• Perinatal
HBV Modes of Transmission
CDC
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Hepatitis B• Acute and chronic forms
§ 2-10% develop chronic disease over 5 years of age
• Asymptomatic or symptomatic§ Clinical illness <5 yrs of age: <10%
(jaundice) >5 yrs of age: 30%-50%• Incubation: 45 – 180 days
§ Average 60-90 days• Most common cause of cirrhosis and
hepatocellular carcinoma worldwideCDC
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United United States States 3-4 M3-4 M
AmericasAmericas12-15 M12-15 M
Africa Africa 30-40 30-40
MM
Southeast AsiaSoutheast Asia30-35 M30-35 M
AustraliaAustralia0.2 M0.2 M
World Health Organization. Weekly epidemiological record. World Health Organization. Weekly epidemiological record. 1999;74:421-428.1999;74:421-428.
Western Western Europe Europe
5 M5 M
170-200 Million (M) Carriers Worldwide170-200 Million (M) Carriers WorldwideHepatitis C: A Global Health Problem
Eastern Eastern Europe Europe 10 M10 M
Far East Far East AsiaAsia60 M60 M
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Acute Hepatitis CAcute Hepatitis C
Chronic Hepatitis Chronic Hepatitis 75%-85 %75%-85 %
Cirrhosis 20 %Cirrhosis 20 %
10-20 years
Hoofnagle JH Hepatology. 1997;26 (suppl 1): 15S-20SDi Bisceglie, Hepatology, 2000
Natural History of Hepatitis CMost patients with chronic HCV infection are asymptomatic
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Hepatitis C: Pathophysiology• Hepatitis C virus (HCV) replicates in liver cells
(hepatocytes)• Immune system responds with inflammation• Inflammation leads to fibrosis and eventually, in
some cases, cirrhosis (scarring)
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Complications of Cirrhosis
• Dangerous impairment of liver function§ Inability to clear toxins from the circulation => jaundice;
hepatic encephalopathy§ Inability to synthesize key proteins (albumin, clotting
factors)• Cancer (hepatocellular carcinoma)• Blockage of portal vein blood flow through the
liver, leading to ascites§ Bacterial peritonitis (infection of the ascites)§ Esophageal varices
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Massive ascites due to hepatocellular carcinoma, with collateral venous dilation
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Other Extrahepatic Manifestations of Hepatitis C• Hematologic:
§ Cryoglobulinemia§ lymphoma
• Rheumatologic: rheumatoid arthritis• Renal: Glomerulonephritis• Dermatologic:
§ Porphyria cutanea tarda§ Cutaneous necrotizing vasculitis§ Lichen planus
• CNS: depression• Systemic: fatigue
Management of Hepatitis C. NIH Consensus Statement, 2002.
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Hepatitis CHIV/HCV COINFECTION• 10%-30% w/ HIV also have HCV• Rate of HCV depends on risk factor
§ Hemophiliacs – >90%§ IDUs – 70%-90%§ MSM – 5%-10%
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HCV/HIV Coinfection• HIV accelerates Hep C liver disease (may
cut time to cirrhosis in half!)
• Hep C may impair immune reconstitution after HAART
• HCC may occur at an earlier age with coinfection
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Hepatitis CHIV/HCV COINFECTION• HCV liver disease is more severe in HIV+• HCV liver disease is now more important
§ HIV deaths are decreasing§ Deaths related to liver disease are increasing
• Effect of HCV infection on HIV/AIDS progression is not known
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Hepatitis CHIV/HCV COINFECTION• HIV treatments can cause liver
problems/liver enzyme elevations§ In some studies these liver problems are
increased in those w/HCV• Some report worsening of HCV liver
disease after HIV treatment is started
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HIV/HCV Treatment• Predictors of success in achieving a
sustained viral response:
• CD4 count greater than 500• HIV RNA levels below 10,000 copies• No alcohol consumption
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Drug interactions in Co-infection
• ddI and d4T plus interferon/ribavirin appear to cause mitochondrial toxicity
• result: lactic acidosis, peripheral neuropathy
• Avoid starting these drugs if plan to treat HCV later
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Ringkasan• HIV yang tidak segera diberi ARV → AIDS• AIDS pintu masuk untuk terjadinya Infeksi
Oportunistik (IO) • Infeksi Oportunistik diterapi sesuai jenis
penyakitnya• Ko-infeksi, infeksi bersamaan dengan HIV• Ko-infeksi tersering HBV, HCV• Terapi ko-infeksi tidak mudah terkait interaksi
obat, efek samping obat dan biaya