AQUIRED IMMUNODEFICIENCY SYNDROME

AQUIRED IMMUNODEFICIENCY SYNDROME

dr. Alwi Mappiasse,Sp.KK.Ph.D

PENDAHULUANMANIFESTASI KLINIK & TREATMENTETIOPATOGENESISTRANSMISIEPIDEMIOLOGIDEFINISI AIDS DAN HIVHIVHuman Immunodeficiency Syndrome Virus spesifik Retrovirus HIV menginvasi sel T helper untuk mereplikasi

A- AcquiredI- ImmuneD- DeficiencyS- Syndrome Ditularkan dari orang ke orangMerusak sistem kekebalan manusia. Kekebalan adalah sistem pertahanan tubuh untuk mempertahankan diri dari serangan infeksi seperti bakteri atau virusPenurunan sistem kekebalan tubuh Orang dengan AIDS mengalami berbagai infeksi oportunistik dan penyakit lainnya.AIDS HIV infections caused millions of morbidity and mortality around the world

20 millions has died from AIDS, 40 millions are alive with HIVHIV-1: world wide; HIV-2: West Africa and India (2001)INDONESIAUNAIDSIndonesia- FKUI-RSCM, mikosis superfisial Kandidosis oral (52,9%) & kuku (0,6%) Dermatofitosis kruris / korporis (3,8%) & kuku (1,3%) Malasseziosis : Pityriasis versicolor (4,5%).

6Transmisi HIV/AIDS

Hubungan seksualDrug UseIBU ANAKDarah yang terinfeksi- Kelompok risiko Mitra seksual multipel tanpa kondom (75-85%) Pengguna narkoba suntik (5-10%) Tranfusi darah (3-5%) Bayi dengan ibu positif HIV (25-35%)

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Hubungan Sosial

HIV tidak menular melalui 899You cannot get HIVSocializing or casually living with people with HIV or AIDSHugging, touching or kissing someone with HIV or AIDSUsing the same clothes, eating utensils, drinking fountains, toilets, telephones or computers as people with HIV or AIDSDonating bloodFrom sweat, spit, tears, sneezing and coughing from an infected personGetting bitten by a mosquito that has bitten an infected personCaring and looking after people with HIV or AIDSWorking with people who are HIV positive

ETIOLOGIHIV HIV-1 HIV-2 Genus Lentivirus, Famili RetroviridaeVirus RNA3 bagian : - external envelop - internal envelop - capsid/inti1011

Envelop gp 120 gp41EnzymReverse transcriptaseIntegrase ProteaseNucleus P17 (matrix) P24 (capsid) P7/P9(nucleocapsid)

The phenotype (or physical appearance/structure) of HIVPATOFISIOLOGI

Daur hidup HIV12Replikasi HIV adsorbsi Glikoprotein/endositosissel reseptor CD4 (sel target) Fusi envelop virus + membran sel Pelepasan kapsid HIV

Transkripsi RNA virus reverse transcriptase DNA virusintegrase Inti selDNA virus >>>13Rekonstruksi

DNA virus (sel hospes) Messenger RNA (mRNA) proteaseProtein virus (maturasi) Budding/lisis sel1415

Steps in HIV replication are illustrated in the diagram.A more detailed description of the steps are below:Binding of gp120 to CD4 and co-receptor on the cell surfaceFusion of the viral envelope with the cell membraneRelease and disassembly of the viral core in the cytoplasmReverse transcription (Reverse transcriptase enzyme translates HIVs single stranded RNA into a provirus made of double stranded DNA) Viral DNA moves into cell nucleus Viral DNA is integrated (by Integrase enzyme) into host genome to form HIV provirusHIV provirus DNA is transcribed back to both viral genomic RNA and viral mRNA , the latter which is translated to HIV polyproteins.The RNA virus and polyproteins are assembled beneath the cell membrane The assembled package becomes enveloped in the host cell membrane as it buds off to form an HIV virion. Further assembly and maturation occurs outside the cell by the protease enzyme, rendering the HIV virion infectious.

16 HIV pada permukaan limfosit CD4

Courtesy of CDCThis transmission electron micrograph of an HIV virion on the surface of a CD4 lymphocyte shows both immature and mature virions. 17HIV SelProtein env gp120 berikatan pada reseptor CD4CD4 : terdapat pd permukaan limposit T, monosit-makrofag. Langerhans, sel dendrit, astrosit, mikrogliaProtein env gp120 berikatan dengan ko-reseptorReseptorCCR5 makrofagReseptorCXCR4 limfositIkatan virus pada membran sel memungkinkan virus mengadakan penetrasi ke dalam selInti virus dilepaskan masuk ke dalam sitoplasma sel targetNow a review of the lifecycle steps in more detail: For attachment and entry into the human cells, HIV use normal proteins on the surface of human cells.HIV attaches to the CD4 cell protein. These receptors occur on CD4 cells, monocyte, and macrophages As second step in entry, HIV binds to co-receptors, which are normally receptors for chemokines. A mutant CCR5 receptor gene that prevents the virus from binding to the cell has been discovered. Homozygosity for this mutant gene is strongly protective against HIV infection. Heterozygous people are not protected from infection but the disease may take longer to develop.18Viral hostSekitar 109 - 1011 virus baru diproduksi tiap hariVirus HIV pada plasma 6 jam Limfosit CD4 terinfeksi oleh HIV 1-6 hariHIV dapat dorman pada sel selama beberapa tahun, khususnya saat sel memori CD4 tidak teraktivasi The extremely high rates of viral replication results in every possible point mutation in the viral genome arising daily. In any given patient, the virus usually varies by 1-6% in the env gene, for example.19

Copyright 1998 Massachusetts Medical Society. All rights reserved.HIV masuk kedalam host melalui epitel mukosaTerjadi dalam 2 hari pertama infeksiInfeksi menjalar ke seluruh jaringan dalam 3 hariInfeksi menyebar ke macrofag jaringan mengaktifkan CD4 sel dalam lymph nodeMasuk dalam peredaran darahMasuk kedalam organ

Early Events in Transmucosal HIV-1 InfectionThe arrows indicate the path of the virus. The viral-envelope protein binds to the CD4 molecule on dendritic cells. Entry into the cells requires the presence of CCR5, a surface chemokine receptor. Dendritic cells, which express the viral co-receptors CD4 and CCR5, are selectively infected by R5 (macrophage-tropic) strains. Within two days after mucosal exposure, virus can be detected in lymph nodes. Within another three days, it can be cultured from plasma. Source: Kahn and Walker. NEJM. 1998; 339:33-39

MANIFESTASI KLINISPenyakit yang sering pada pasien AIDS: Penyakit saluran nafas Penyakit saluran cerna Penyakit susunan saraf Keganasan Infeksi oportunistik lain

20Infeksi oportunistik

21Thus HIV infected pts are at risk for a whole host of opportunistic infections including: fungal, viral, mycobacterial, parasitic, and bacterial infections as well as lymphomas kaposis sarcoma, neurologic manifestations, and HIV nephropathy

And as a note, Most of these conditions are opportunistic infections that generally do not affect healthy people. However, In people with AIDS, these infections are often severe and sometimes fatal because the immune system is so ravaged by HIV that the body cannot fight off certain bacteria, fungi, and microbes.MANIFESTASI KUTANEUSManifestasi mukokutaneusSarkoma kaposiVirus : herpes simpleks, herpes zoster,epstein barr, human papiloma, poks.Jamur : dermatofitosis, kandidiasis,kriptokokosis & histoplasmosis,Lain-lain : dermatitis seboroik, erupsipapular pruritus22Cont Sarcoma Kaposi - Penyakit neoplastik vascular- Etiologi : HHV-8 - Prevalensi di dunia 34%- Lokasi : ekstremitas inferior, rongga, gusi mulut dan palatum

23Cont..Lesi : macula, papul, nodul, /tumor merah / ungu, hiperpigmentasi, oval, simetris, mengikuti garis kulit

- Terapi Topikal : gel asam tretinoin 0.1% Terapi anti retro viral kombinasi protease inhibitor + 2 virostatik Interferon (IFN)- dan IFN-

24Cont..Terapi Kemoterapi doxorubicin dan daunorubicin paclitaxel / anthracyclin, liposomal

Tindakan : krioterapi (N2 cair), laser CO2, fotokoagulasi sinar infra merah, bedah eksisi, elektrofulgurasi, radiasi25Cont.. Infeksi virus Herpes simpleks - Herpes labialis, herpes genitalis. - Prevalensi 20%. - Klinis : *Prodromal : nyeri / rasa terbakar *Lesi : erupsi nyeri,vesikuler, eritematosa krusta

26Cont..Terapi : asiklovir + anti retroviral. Herpes simpleks rekuren asiklovir 200 mg p o 5 kali/hariInfeksi yang luas asiklovir 5 mg/kg i v setiap 8 jam 7-10 hari27Herpes simpleks

HERPES GENITAL

28Cont.. Herpes zoster (HZ) - Prevalensi 6-9% - Lesi : eritema vesikel berkelompok, dasar kulit eritematosa dan edema. Vesikel : cairan jernih keruh (abu-abu) pustul & krusta. - Terapi : obat anti retro viral + thymidine kinase inhibitors29Cont..- Thymidine kinase inhibitors asiklovir, valasiklovir & famsiklovir. asiklovir 800 mg p o 5 kali/hari 7-10 hari atau 10 mg/kg iv setiap 8 jam 10 hariBila resisten : foskarnet, sidofovir & vidarabin i v Herpes zoster oftalmika spesialis mata

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Herpes Zoster

31Cont Epstein-Barr virus (EBV) - Oral hairy leukoplakia - Prevalensi 2.5-10%. - Lesi : papul filiformis, putih, asimtomatik,potensi ganas (-) - Lokasi : tepi lidah, jarang bilateral - DD/ kandidiasis oral, liken planus, & lidah geografik.

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Oral Hairy Leukoplakia.33Cont.. Human papilloma virus (HPV) - Kondiloma akuminata - Lesi : vegetasi bertangkai, kemerahan / kehitaman (lesi lama), permukaan berjonjot (papilomatosa) vegetasi >> bunga (flourish atau cauliflower- like growths) - Karsinoma sel skuamosa HPV serotipe 16 dan 18 Terapi : Kemoterapi podofilin, asam trikloroasetat (TCA ), 5-fluorourasil (5-FU). Tindakan bedah listrik/elektrokauterisasi ; bedah beku (N2, N2O cair); bedah, scalpel; laser CO2 Sistemik interferon & imunoterapi. 34

Kondiloma Akuminata35Cont.. Virus poks- Moluskum kontagiosum - Lesi : papul miliar, lentikular , putih seperti lilin, berbentuk kubah (delle) massa putih- Lokasi : wajah, leher, badan dan ekstremitas- Terapi : mengeluarkan massa badan moluskum alat ekstraktor komedo, jarum suntik / kuret. elektrokauterisasi / bedah beku : perdarahan - Tinea cruris (jock itch) - Tinea corporis (ringworm) - Terapi : Topikal : antimikotikSistemik : Griseofulvin 0,5-1 gram, Ketokonazole 200 mg / hari, Terbinafine 62,5-250 mg/hari.

37Cont.. Kandidiasis

- Candida albicans 60 % orang normal- Kandidiasis oral/thrush >> - Lesi : pseudomembran putih coklat muda kelabu (lepas basah dan merah), dapat terpisah-pisah, seperti kepala susu - Lokasi : lidah, palatum mole, pipi bagian dalam >>- Kasus berat : faring dan esofagus disfagia- Sulkus koronarius glans penis, vagina, anus.. - Kandidiasis sistemik.

38Dikenal 4 tipe candidiasis oral:Tipe pseudomembranosa = thrush tersering dijumpai dimana saja pd cavum oris2. Tipe Hiperplastik Mirip pseudomembranous tetapi melekat erat pada jaringan3. Tipe Eritematosa Tampak sebagai lesi patch eritem pada area mukosa Pada lidah tampak sebagai daerah atrofi, halus tanpa tekstur4. Tipe angular cheilitis Dijumpai fisura pada sudut mulutCont..- Terapi Lokal : larutan gentian violet, nistatin, amfoterisin B, grup azol Sistemik : tablet nistatin, amfoterisin B (i v), klotrimazol 500 mg per vaginam, ketokonazol 2x200 mg / hari, & itrakonazol 2x100 mg / hari 40

Oral thrush41Cont Mikosis ProfundaKriptokokosis - Lesi : selulitis, papul, ulserasi, / papul kubah translusen (delle) Histoplasmosis- Lesi : papul merah, erupsi seperti selulitis, ulserasi, papul akneiform, / lesi seperti moluskum- Terapi : amfoterisin 0.5 mg/kg/hari i v / itrakonazole 200 mg p o42Cont.. Kelainan kulit lainnya Dermatitis seboroik (83 %) - Lesi : eritema & skuama berminyak + eksudasi & krusta tebal, kekuningan, batas agak kurang tegas, berbau tidak sedap. - Lokasi : kepala, wajah, dada, aksila, lipat paha, dan genital. 43Cont..- Terapi Topikal : kortikosteroid, likuor karbonis detergens (LCD) 2-5%, resorsin 1-3%, / sulfur presipitatum 4-20%, asam salisilat 3-6%, ketoconazole Sistemik : ketokonazole 200400 mg per hari44

Dermatitis seboroik45

Dermatitis seboroik46Cont.. Erupsi papular pruritus- Lesi : papul merah / seperti kulit, kecil, sangat gatal- Lokasi : kepala, leher, & tubuh bagian atas. Etiologi : ? - Terapi : topikal : prednison sistemik : antihistamin, prednison tindakan : fototerapi UV B (> efektif)47

Erupsi papular pruritus48

PEMERIKSAAN PENUNJANGPemeriksaa laboratorium : Cara langsung- Antigen virus Polymerase Chain Reaction (PCR) & b-DNA viral load tes diulangi setiap 3 bulan, lama tes 4-7 hr Hasil negatif bila : PCR viral load test : 10%- Diare kronik > 1 bulan, etiologi ?- Demam > 1 bulan, etiologi?- Kandidosis mulut- Oral Hairy leukoplakia- Tuberkulosis paru 1 tahun terakhir- Infeksi bakteri berat pneumonia- Acute necrotizing ulcerative stomatitis / gingivitis Baring di tempat tidur 1 bulanKriptokokosis, ekstrapulmonerCytomegalovirus (CMV) pada organ selain hepar, lien / KGBInfeksi Herpes simplex virus (HSV), mukokutan > 1bulanProgressive multifocal leukoencephalopathy (PML)Mikosis diseminata histoplasmosisKandidiasis esofagus, trakea, bronkus / paruMikobakterialis atipikal diseminataSeptikemia salmonelosis non tifoidTB EkstrapulmonerLimfomaSarkoma Kaposi (KS)Enselopati HIV 4. Tingkat klinis 455ContKelainan hasil pemeriksaan laboratorium:- Jumlah CD4 - Rasio CD4/CD8 (nilai normal 1,1:1,8)- Anemia, leukopenia, trombositopenia, limfositopenia, hipergamaglobulinemia - Respon limfosit - Anergi terhadap uji kulit lambat- Kompleks imun 56Cont CDC AIDS :- HIV positif - CD4 < 200 per L darah / 14% dari seluruh limfosit Kriteria Limfadenopati Generalisata Persisten :- Pembesaran KGB 2 lokasi di luar inguinal selama 3 bulan.- Tidak ada penyakit lain yang menyebabkan limfadenopati.- Biopsy pola reaktif.57

DIAGNOSIS BANDINGKeganasan Limforetikular Pasien kemoterapi kanker, imunosupresanTerapi kortikosteroid jangka lama Kondisi malnutrisi, penyalah guna obat, dan demensia Keadaan imunodefisiensi primerCommon Variable Immunodeficiency (CVID) 58PENATALAKSANAAN Indikasi antiretroviral : - Infeksi HIV tahap lanjut stadium IV stadium III CD4 5 tahun.Tanpa obat anti retro viral 1 tahun infeksi oportunistik / keganasan >>69

PENUTUPPencegahan !!Pendidikan kelompok risiko : mitra seksual multipel, penyalahguna obat-obatan terlarang intra vena, dan cara hubungan seksual Anjuran supaya pasien HIV/AIDS tidak menyumbangkan darah, organ, atau cairan semen, dan mengubah kebiasaan seksualnyaSkrining donor darah antibodi HIV

70Terima Kasih

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