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Learning Objective

Menjelaskan tentang imunodefisiensi


Klasifikasi
Etiologi
Patogenesis
Manifestasi klinik
Komplikasi
Menjelaskan tentang HIV
Klasifikasi
Etiologi
Patogenesis
Manifestasi klinik
Komplikasi
Differential Diagnosis
Pemeriksaan
Penatalaksanaan
Pencegahan
LO 1
Definisi imunodefisiensi

Rentan infeksi
Penurunan atau
ketiadaan respon
imun normal
Cacat
Reaktivasi infeksi
perkembangan &
laten
fungsi sistem imun

Peningkatan
beberapa kasus Rentan infeksi
kanker

Abbas Dorland
Manifestasi Klinis
Infeksi, rekuren, kronis dengan ciri :
Sebab tidak biasa
Flora normal
Mikroba lingkungan

Gejala yang sering ditemukan:


Diare kronik
Hepato-splenomegali
Autoantibodi atau penyakit autoimun
Gangguan Fungsi Sistem Imun Umum
Gangguan fungsi sistem Penyakit yang menyertai
imun
Defisiensi
Sel B Infeksi bakteri rekuren seperti otitis media, pneumonia
rekuren.

Sel T Kerentanan meningkat terhadap virus, jamur, dan


protozoa.

Fagosit Infeksi sistemik oleh bakteri yang dalam keadaan biasa


mempunyai virulensi rendah, infeksi bakteri piogenik.
Komplemen
Infeksi bakteri, autoimunitas.

Fungsi yang berlebihan


Sel B Gangguan monoklonal.

Sel T Kelebihan sel Ts yang menimbulkan infeksi dan penyakit


limfoproliferatif.
Fagosit Hipersensitifitas, beberapa penyakit autoimun

Komplemen Edem angioneurotik akibat tidak adanya inhibitor esterase


Gejala Defisiensi Imun
Ruam kulit
Diare
Pertumbuhan terganggu
Hati dan limpa membesar
Abses rekuren atau osteomielitis
Penurunan resistensi terhadap virus (jika ada
defisiensi seluler)
Klasifikasi Imunodefisiensi
Imunodefisiensi dapat
mengenai salah satu dari 4
komponen sistem imun:
Primary / Sel B (antibodi)
Congenital Sel T
Imunodefisiensi Komplemen
Secondary / Fagosit
Acquired Secara klinis, sering dijumpai
infeksi rekuren
Bakteri piogenik (c/ :
staphylococcus) def. sel B
Jamur, virus, protozoa
def. sel T
ETIOLOGI
ETIOLOGI
ETIOLOGI
DEFISIENSI IMUN NONSPESIFIK

1. DEFISIENSI KOMPLEMEN
menimbulkan infeksi bakteri yang rekuren dan
penyakit autoimun
1.1 DEFISIENSI KOMPLEMEN KONGENITAL
Defisiensi inhibitor Berhubungan dengan angioedem herediter
esterase C1 Akibatnya : aktivitas C1 yang tidak dapat di
kontrol produksi kitin permeabilitas
kapiler.
Defisiensi C2 dan C4 Menimbulkan penyakit serupa LES karena
gagal eliminasi kompleks imun
Defisiensi C3 Berhubungan dengan infeksi mikroba piogenik
Fragmen C5 tidak diproduksi
Rx berat fatal
Defisiensi C5 Rentan infeksi bakteri yang berhubungan
dengan gangguan kemotaksis

Defisiensi C6, C7, dan Rentan terhadap septikemi meningokok dan


C8 gonokok oleh karena lisis melalui jalur
komplemen adalah mekanisme kontrol utama
dalam imunitas terhadap neseria.
1.2 DEFISIENSI KOMPLEMEN FISIOLOGIK
Ditemukan pada neonatus karena kadar C3, C5, dan faktor B
rendah
1.3 DEFISIENSI KOMPLEMEN DIDAPAT
Defisiensi C1q, r, s Berhubungan dengan edem
angioneurotik herediter
tidak punya inhibitor esterase
C1
Defisiensi C4 Pada beberapa penderita SLE
Defisiensi C2 Pada penderita SLE.
Defisiensi C3 Infeksi bakteri rekuren
Defisiensi C5-C8 Rentan terhadap infeksi
terutama Neiseria
Defisiensi C9 Tidak menunjukkan tanda
infeksi rekuren
DEFISIENSI IMUN NONSPESIFIK

2. DEFISIENSI IFN & LISOZIM

A. DEFISIENSI IFN KONGENITAL


Menimbulkan infeksi mononukleosis yang fatal

B. DEFISIENSI IFN & LISOZIM DIDAPAT


Pada malnutrisi protein / kalori
DEFISIENSI IMUN NONSPESIFIK

3. DEFISIENSI SEL NK

A. DEFISIENSI KONGENITAL
Pada penderita osteoporosis
Kadar IgG & IgA

B. DEFISIENSI DIDAPAT
Akibat imunosupsresi / radiasi
DEFISIENSI IMUN NONSPESIFIK

4. DEFISIENSI SISTEM FAGOSIT

A. DEFISIENSI KUANTITATIF
Karena penurunan produksi atau peningkatan
destruksi

B. DEFISIENSI DIDAPAT
Pengaruhi fungsi fagosit kemotaksis,
menelan/memakan, dan membunuh mikroba
intraselular
4.2.1 Chronic Granulomatous Disease
Defek netrofil ketidakmampuan membentuk peroksid
hidrogen atau metabolit oksigen toksik lainnya.
4.2.2 Defisiensi Glucose-6-phosphate
dehydrogenase
Mempunyai gambaran klinik seperti CGD. Diduga akibat
defisiensi generasi NADPH. Dalam keadaan normal,
fagositosis akan mengaktifkan oksidase NADPH yang
diperlukan untuk pembentukan peroksidase yang berguna
untuk membunuh kuman intraselular.

4.2.3 Defisiensi Chediak-Higashi


Netrofil mengandung lisosom besar abnormal yang dapat
bersatu dengan fagosom tetapi terganggu kemampuan
melepas isinya, sehingga proses menelan dan
menghancurkan menjadi terlambat. Aktivitas sel NK, enzim
lisosom menurun.
4.2.4 Sindrom Job

Kemampuan netrofil untuk menelan/memakan tidak


menunjukkan kelainan, tetapi kemotaksis terganggu. Kadar
IgE serum sangat tinggi dan dapat ditemukan eosinofilia.

4.2.5 Sindrom Leukosit Malas (lazy leucocyte)

Jumlah neutrofil menurun, respons kemotaksis dan


respons inflamasi juga terganggu.

4.2.6 Defisiensi Adhesi Leukosit

Gangguan penyembuhan luka. Leukosit menunjukkan


defek adhesi dengan permukaan endotel dan antar
leukosit (agregasi), kemotaksis dan aktifitas fagositosis
yang buruk. Efek sitotoksik neutrofil, sel NK, dan sel T juga
terganggu.
DEFISIENSI IMUN SPESIFIK

1. DEFISIENSI KONGENITAL / PRIMER

A. DEFISIENSI IMUN PRIMER SEL B


1. X-linked hipogamaglobulinemia
Pre-sel B yang ada dalam kadar
normal tidak dapat berkembang
menjadi sel B yang matang
2. hipogamaglobulinemia sementara
Pada bayi bila sintesis terutama IgG
terlambat.
DEFISIENSI IMUN SPESIFIK

1. DEFISIENSI KONGENITAL / PRIMER

A. DEFISIENSI IMUN PRIMER SEL B


3. Common variable hipogamaglobulinemia
Jumlah sel B & IgG normal tapi
pelepasannya terganggu
4. Defisiensi imunoglobulin selektif
Penurunan kadar satu atau lebih Ig, tetapi
dengan kadar Ig yang lain normal atau
meningkat
Lumphocyte B (Antibody) deficiencies
Abbas, Cellular & Mollecular Immunology 6th ed, Saunders Elsevier
Disease
A. Agammaglobulinemia
Immune Deficiency
Fx Deficiencies Mekanisme

X-linked Defek checkpoint reseptor pre-B


Semua isotype Ig serum,
Autosom resesif jumlah sel B Defek checkpoint reseptor pre-B; mutasi IgM
heavy chain (m), surrogate light chain, Iga
B. Hypogammaglobulinemia/isotype
Def. IgA selektif IgA, risk inf. Bakteri & protozoa Mutasi TACI (transmembran activator, calcium
(giardia lamblia) modulator, cyclophilin ligand inhibitor)
Def. IgG2 selektif Risk inf bakteri Delesi lokus g2 IgH
CVID Hypogammaglobulinemia, jml sel Mutasi ICOS (inducible costimulator) & TACI
B n
ICF syndrome Hypogammaglobulinemia, defek Mutasi DNMT3B (DNA methyl transferase 3B)
sel T ringan
C. Hyper IgM syndrome
X-linked Defek aktivasi sel B terkait ThC, Mutasi CD40L
makrofag, dendritic; defek mutasi
Autosom resesif Mutasi CD40, NEMO (NF-kB essential
somatik & pbntkan pusat
w/ defek CMI modulator)
germinal; defek CMI
Autosom resesif Defek mutasi somatik & switching Mutasi AID (activation induced cytidine
w/ defek antibodi isotype deaminase), UNG (uracil N-glycosylase)
DEFISIENSI IMUN SPESIFIK

1. DEFISIENSI KONGENITAL / PRIMER

B. DEFISIENSI IMUN PRIMER SEL T


1. Sindrom DiGeorge
Penderita tidak /sedikit memiliki sel T
dalam darah, kelenjar getah bening &
limpa
2. Kandidiasis mukokutan kronik
Infeksi jamur biasanya nonpatogenik
K.albicans pada kulit & selaput lendir
disertai gangguan fungsi sel T yang selektif
Lymphocyte T Defects
Abbas, Cellular & Mollecular Immunology 6th ed, Saunders Elsevier
Disease
A. Defek ekspresi MHC
Immune Deficiency
Fx Deficiencies Mekanisme

Bare lymphocyte Defek ekspresi MHC II, defisiensi Defek fc transkripsi yg atur ekspresi gen MHC II
syndrome CD4TC; defek CMI & T (CIITA, RFXANK, RFX5, RFXAP)
dependent humoral immunity
Defisiensi MHC I Mutasi TAP1 (transporter associated w/ antigen
MHC I; CD8TC
processing), TAP2, tapasin
B. Defek signal sel T
Proximal TCR defek CMI & T dependent Mutasi gen CD3, CD45
signaling defects humoral immunity
Wiskott-Aldrich Defek aktivasi sel T & mobilitas Mutasi defek TCR dependent actin-
syndrome limfosit cytoskletal rearrangement
C. Familial hemophagocytic lymphohistiocytoses
X-linked Unctrl EBV induced B cell prolif; Mutasi SAP (SLAM associated protein)
lymphoproliferative Unctrl aktivasi makrofag & CTL;
syndrome Defek fx CTL & NKC
Perforin deficiencies Unctrl aktivasi makrofag & CTL; Mutasi perforin
Defek fx CTL & NKC
Granule fusion Unctrl aktivasi makrofag & CTL; Defek cytotoxic granule exocytosis; mutasi
defects Defek fx CTL & NKC RAB27A, MUNC13-4 (LYST@Chediak-Higashi)
DEFISIENSI IMUN SPESIFIK

1. DEFISIENSI KONGENITAL / PRIMER

C. DEFISIENSI KOMBINASI SEL B & SEL T BERAT


1. SCID
2. Sindrom Nezelof
3. Sindrom Wiskott-Aldrich
4. Ataxia telangiektasi
5. Defisiensi adenosine deaminase
SCID
Abbas, Cellular & Mollecular Immunology 6th ed, Saunders Elsevier
Disease
A. Defek signal sitokin
Immune Deficiency
Fx Deficiencies Mekanisme

SCID X-linked Mutasi rantai g reseptor umum sitokin signal


T sel , B sel n, IL7 g3 perkembangan sel T
serum Ig
Autosom resesif Mutasi JAK3, rantai IL-2Ra, IL-7Ra
B. Defek jalur salvage nukleotida
Defisiensi ADA Sel T, B, NK progressif, Akumulasi metabolit toksik @ limfosit
Defisiensi PNP serum Ig Akumulasi metabolit toksik @ limfosit
C. Defek rekombinasi V(D)J
Defisiensi RAG1/RAG2 Sel T & B, defisien, Defek pemisahan @ rekombinasi V(D)J
Defek ARTEMIS serum Ig Gagal bongkar hairpin @ rekombinasi V(D)J
D. Perkembangan timus defektif
Defek checkpoint pre- Mutasi CD45, CD3d, CD3e, Orai1 (CRAC
TCR T sel , B sel n, serum channel component)
Ig
DiGeorge syndrome Delesi 22q11, mutasi faktor transkripsi TBX1
E. Defek lain
Disgenesis retikular Sel T, B, myeloid Mutasi tak teridentifikasi
SCID
Kelainan sistem imun krn kegagalan sel induk
untuk berdiferensiasi menjd sel T / sel B limfosit
dalam peredaran darah
Sangat rentan hampir pada smua infeksi mikroba
Gejala sejak bayi (3 bln) jika tidak diobati umur
<1thn
Gejala khas : limfopenia
Diturunkan melalui kromosom X atau autosom
resesif
SCID
Klasifikasi SCID :
X-Linked SCID pada laki2
Mutasi rantai (c) memblok IL-7 maturasi sel T
Mediated cell immunity
Imunitas humoral
NK Cell
Autosomal SCID
Dapat terjadi defisiensi ADA, PNP, RAG efek :
Maturitas sel T
Mediated cell immunity
Imunitas humoral
50% defisiensi ADA kelebihan ATP dan deoxyATP yang
bersifat toksik
- Treatment for SCID
Preventing infections
Children with SCID need to be protected from germs.
They are treated with antibiotics to prevent infections such as Candida
albicans (a type of yeast) and Pneumocystis pneumonia (PCP)
infections.
They will also be given intravenous immune globulin (IVIG). Immune
globulin is also called immunoglobulin or gammaglobulin. It contains
antibodies that would normally be made by healthy B cells to help the
body fight infection. Immune globulin is usually infused into a vein.
Patients with SCID usually require IVIG infusions once every 3-4 weeks.
Enzyme therapy for ADA deficiency SCID
The standard treatment for ADA deficiency SCID is treatment with a
form of the ADA enzyme called PEG-ADA. Treatment with PEG-ADA is
effective in about 90% of children.
Transplant
The only known cure for SCID is a bone marrow or cord blood
transplant (also called a BMT)
2. Sindrom Nezelof
Rentan terhadap infeksi rekuren berbagai mikroba.
Imunitas sel T menurun, defisiensi sel B variabel dan kadar
Ig spesifik dapat rendah, normal, atau meningkat
(disgamaglobulinemia). Respon antibodi terhadap antigen
spesifik biasanya rendah atau tidak ada
3. Wiskott-Aldrich Syndrome
Common signs and symptoms of WAS usually appear soon
after birth or within the first year of life:
Bleeding easily because of too few normal platelets. This
may include tiny red spots under the skin (petechiae),
bruises, blood in bowel movements, bleeding gums and
nose bleeds.
Frequent infections because of too few B cells and T
cells. Common infections are ear and sinus infections
and pneumonia.
Eczema (an itchy rash) of the skin.
4. Ataxia telangiectasia
penyakit autosomal resesif yang mengenai saraf,
endokrin, dan sistem vaskular. Klinis ditemukan
defisiensi selektif IgA dengan kelainan variabel yang
mengenai imunoglobulin lain
Ciri klinisnya : gerakan otot yang tidak terkoordinasi,
dilatasi pembuluh darah kecil, limfopenia dan
penurunan IgA, IgE dan kadang IgG
5. Defisiensi Adenosin Deaminase
Adenosin deaminase tidak ditemukandalam semua
sel. Hal ini berbahaya karena kadar toksik berupa ATP
dan deoxy-ATP dalam sel limfoid akan meningkat.
WARNING SIGNS OF PRIMARY
IMMUNODEFICIENCY
4 STAGES OF IMMUNOLOGIC TESTING WHEN
PRIMARY IMMUNODEFICIENCY IS SUSPECTED
Therapy 4 primary deff
Tujuan utama:
Minimalkan & kendalikan infeksi
Ganti komponen sistem imun yg rusak / hilang dg transfer
adoptif atau transplantasi

Pendekatan yg dilakukan:
Imunisasi Pasif: tu agammaglobulinemia
Transplantasi SSTL: treatment of choice berbagai congenital
immuno deficiency, tu SCID dengan defisiensi ADA, Wiskott-
Aldrich syndrome, bare lymphocyte syndrome, LAD
(Leukocyte Adhesion Deficiencies)
Terapi penggantian enzim: untuk defisiensi ADA & PNP,
namun biasanya hanya untuk jangka pendek
Terapi penggantian gen dengan stem sel yang memperbarui
diri: masih dalam pengembangan
DEFISIENSI IMUN SPESIFIK

2. DEFISIENSI IMUN SPESIFIK

A. KEHAMILAN
Peningkatan aktivitas sel Ts atau oleh efek supresif faktor
humoral yang dibentuk trofoblas untuk kelangsungan
hidup fetus
B. USIA TAHUN PERTAMA
Neonatus jumlah sel T yang tinggi, tapi masih naive
tidak memberikan respon yang adekuat terhadap antigen.
C.USIA LANJUT
Rentan terkena infeksi terjadi atrofi timus, fungsi timus
menurun. Jumlah sel T memori meningkat tapi makin sulit
berkembang
DEFISIENSI IMUN SPESIFIK

3. DEFISIENSI IMUN DIDAPAT

A. MALNUTRISI
B. INFEKSI
C. OBAT, TRAUMA, TINDAKAN KATETERISASI DAN BEDAH
D. PENYINARAN
E. PENYAKIT BERAT
F. KEHILANGAN IMUNOGLOBULIN / LEUKOSIT
G. STRES
H. AGAMAGLOBULINEMIA DENGAN TIMOMA
I. AIDS
Defisiensi Imun Spesifik Sekunder
Defisiensi Imun Spesifik Sekunder
Defisiensi Imun Spesifik Sekunder
Faktor faktor yang menimbulkan defisiensi
imun sekunder
Pemeriksaan untuk imunodefisiensi
Pemeriksaan darah tepi
Hb
Leukosit total
Hitung jenis leukosit (presentasi)
Morfologi limfosit
Hitung trombosit
Pemeriksaan imunoglobulin kuantitatif (IgG, IgA, IgM, IgE)
Kadar antiodi terhadap imunisasi sebelumnya (fungsi IgG)
Titer antibodi tetanus, difteri
Titer antibodi H. influenzae
Penilaian komplemen (komplemen hemolisis total = CH50)
Evaluasi infeksi (LED atau CRP, kultur, dan pencitraan yang
sesuai)
Komplikasi imunodefisiensi
Perkembangan penyakit
Penyakit yang hilang timbul
Peningkatan resiko terkena kanker atau tumor
tertentu
Infeksi oportunistik
LO 2
Struktur HIV
Struktur virus HIV-1
terdiri atas 2 untaian
RNA yang identik dan
berhubungan dengan
p17 dan p24 berupa inti
polipeptida.

Semua komponen
diselubungi envelop
membran fosfolipid dari
sel pejamu.

Protein gp120 dan gp41


ditemukan dalam
envelop.
HIV
HIV
Target sel infeksi HIV:
- limfosit T CD4+
- makrofag
- sel dendritik
Siklus hidup HIV :
- infection cells
- production of viral DNA
- integration into the host genom
- expression of viral genes
- production of viral particles
Siklus Hidup HIV
Mechanisms of immune evasion by HIV

HIV has an extremely high mutation rate because


of error-prone reserve transcription, and in this
way it may evade detection by antibodies or T
cells generated in respone to viral proteins
HIV-infected cells may evade CTLs through down
regulation of class I MHC molecule expression
HIV infection may inhibit cell-mediated immunity
Clinical features of HIV
Phase of disesae Clinical feature
Acute HIV disease Fever, headaches, sore throath with pharyngitis,
generalized lymphadenopathy, rashes

Clinical latency period Declining blood CD4+ T cell amount


AIDS Opportunistic infections :
Protozoa (toxoplasma crytosporodium)
Bacteria (mycobacterium avium, nocardia, salmonella)
Fungi (candida, cryptococcus neoformans, coccidioides
immitis, histoplasma capsulatum, pneumocytis)
Viruses (cytomegalovirus, herpes simplex, vericella-
zooster)

Tumors :
Lymphomas
Kaposis sarcoma
Cervical sarcoma

Encephalopathy
Wasting syndrome
Clinic Manifestation
Diarrhea that persists Mouth disorders
Excessive sweating, night Gingivitis
sweats Oral hairy leukoplakia of
Fatigue that persists tongue, caused by a viral
Fever that persists infection
General feeling of discomfort, Oral thrush
illness, or lack of well-being Pain, loss of sensation, and
Herpes zoster infections that inability to control muscles
keep coming back (peripheral neuropathy)
Joint pain Skin disorders
Swollen lymph glands Fungal infection of the skin
Weight loss or nails
Molluscum contagiosum
Seborrheic dermatitis
TRANSMISSION OF HIV
Patogenesis
AIDS
Pengelompokkan infeksi dan kondisi
penderita HIV
STADIUM INFEKSI & KONDISI

Stadium I Infeksi HIV asimptomatik tidak dikategorikan sebagai AIDS

Stadium II Termasuk manifestasi membran mukosa kecil dan ISPA berulang

Termasuk diare kronik yang tidak dapat dijelaskan selama >1bulan,


Stadium III
infeksi bakteri parah, dan TBC

Termasuk toxoplasmosis otak, candidiasis esofagus, trakea,


Stadium IV
bronkus atau paru-paru, dan sarkoma kaposi indikator AIDS
Klasifikasi penderita HIV
Pembawa virus tanpa tanda
asimptomatik imunosupresi

Persistent Generalized
Lymphadenopathy ada limfadenopati
(PGL)
Penderita HIV
simptomatik : gejala
AIDS-related complex
kelelahan, demam &
(ARC)
kerusakan sistem imun

simptomatik : ancaman
jiwa karena infeksi
Full blown AIDS
oportunistik & sarkoma
Kaposi
Kayser, Medical Microbiology 2005 Thieme

HIV/AIDS (CDC)

CDC (Centers for Disease Control) classification of HIV infection.


The number of CD4+ T cells and the occurrence of so called AIDS-defining diseases
determine whether an HIV-positive patient is categorized as a case of AIDS.
The probability that an AIDS-defining disease will occur rises precipitously at CD4+ cell
counts below 200.
Clinical categories HIV/AIDS
A: Asymptomatic or acute (primary) HIV infection; persistent generalized
lymphadenopathy (LAS)
B: Symptoms indicative of weakened cellular immune defenses, but no AIDS defining
diseases.
C: AIDS-defining diseases:
Viruses Bacteria
HSV: chronic ulcer, esophagitis, bronchitis, Recurrent salmonellar septicemia
pneumonia Recurrent pneumonia
VZV: generalized zoster Mycobacterial tuberculosis, pulmonary and
CMV: retinitis, encephalitis, pneumonia, extrapulmonary forms
colitis Opportunistic mycobacteria (M. avium, etc.),
JC virus: progressive multifocal disseminated or extrapulmonary
leukoencephalopathy Protozoans
HIV: encephalitis Cryptosporidium: chronic diarrhea
HIV: wasting syndrome Isospora belli: chronic diarrhea
Fungi Toxoplasma gondii: encephalitis
Candida: esophagitis, pneumonia, bronchitis Malignomas
Histoplasma, Cryptococcus neoformans, Kaposi sarcoma
coccidiosis: extrapulmonary, disseminated Invasive cervical carcinoma
Pneumocystis carinii: pneumonia B-cell lymphoma EBV-positive
KOMPLIKASI HIV
T. Respiratori : bronkhitis akut
T. kardiovaskular : HIV yang berhubungan dengan
kardiomiopati
Orofaring dan GI : trush, AIDS enteropati
Hepatobiliary : hepatitis B,C, granulomatous hepatitis
Ginjal dan genital : vaginitis
Sistem endokrin dan gangguan metabolik : hipogonadisme
Reumatologik : alergi obat
hepatopoietik : limfadenopati
Dermatologik : psoriasis
Laboratory diagnosis HIV
The following HIV diagnostic procedure is now recommended:
1.HIV antibody screening test diagnose an HIV infection.
2.If the test result is positive, a second serum specimen should be
tested to confirm the result and exclude confusion of sera.
3.If the initial screening test is negative, but a (primary) HIV infection is
justifiably suspected, HIV antigen can be tested, for instance using the
combination test.

Diagnostic tools to confirm HIV infections:


HIV antibody detection.
HIV antigen detection.
Rapid HIV test.
PCR.
Laboratory diagnosis HIV
HIV antibody detection.
EIA screening tests using genetically engineered or synthesized viral antigens
(first to third generation of screening tests). Every positive result requires
confirmation by an alternative test (Western blot). The fourth-generation
screening tests simultaneously detect antibodies to HIV 1 and 2 and p24
antigen (combination test) and are thus capable of detecting primary infections
that are still antibody-negative.

HIV antigen detection.


A viral protein is detected in serum, usually capsid protein p24. The p24 antigen
is detectable in serum as early as two weeks after infection and disappears
again after eight to 12 weeks. Following a clinically stable latency period, HIV
antigen can become detectable months or years later (transitory or persistent).
This renewed appearance of HIV antigen is usually followed by manifest AIDS
and is therefore a negative prognostic sign.
Laboratory diagnosis HIV
Rapid HIV test.
Antibody-based tests are available for rapid diagnosis in medical practices,
hospitals, and health centers. Their specifications are equivalent to the third-
generation screening tests.

PCR.
The most important application of the polymerase chain reaction today is to
determine the so-called viral load, whereby a commercially available
quantitative RT-PCR (reverse transcriptase PCR) is used to determine the
number of viral RNA molecules per ml of blood, taking into account the added
standard amounts of HIV RNA (quantification standard). This test provides a
prognostic estimate of how great the risk of progression to AIDS is
(manifestation of an AIDS-defining disease). It can also be used to monitor the
success of therapy with RT and protease inhibitors.
Therapy HIV
Three classes of substances are available for HIV therapy:
Nucleosidic (or nucleotidic) reverse transcriptase
inhibitors (NRTI) (for example: azidothymidine, AZT;
lamivudine, 3TC; didanosine, ddI, etc.). These are
nucleoside analogs that bind to the active center of the
enzyme are integrated in the DNA strands, resulting in
chain termination.
Nonnucleosidic reverse transcriptase inhibitors
(NNRTI) (for example: efavirenz, EFV; nevirapine, NVP,
etc.). This class of substances also inhibits the
production of viral cDNA by reverse transcriptase, but
does not prevent viral production by infected cells.
Protease inhibitors (PI) (for example: indinavir, IDV;
ritonavir, RTV; saquinavir, SQV, etc.): PIs inhibit viral
protease and thus viral maturation.
Therapy HIV

To avoid development of resistant HIV variants, a


combination of at least three drugs from at least two
substance classes is usually administered. The following
combinations are currently established practice:
a) One PI and two NRTIs
b) One NNRTI and two NRTIs
c) Two PIs and one or two NRTIs
d) One PI and one NNRTI, alternatively with one or two NRTIs
as well;
e) Three NRTIs
a) and b) appear to produce the best long-term results.
Terapi : Obat Antiretroviral
Fungsi obat anti-retroviral
Fungsi Reverse transciptase inhibitors :
berlawanan dengan DNA transkripsi yang
fungsinya untuk mesintesis rantai DNA

Fungsi Protease Inhibitors :


menghambat siklus hidup HIV
menghambat respon enzim untuk
pembentukan protein struktur HIV
Epidemiology & Prevention HIV
HIV is transmitted by blood, blood products, and sexual intercourse.
The virus can also be transmitted from mother to child in intrauterine
infection, perinatal transmission, or the mothers milk.
Infection via saliva or insect bite has not been confirmed.
Accordingly, three rules of behavior are now propagated to prevent the
spread of HIV:
Use a good-quality condom for each act of sexual intercourse. (how good
is good???)
For i.v. drug consumption use only sterile syringes and needles; never
share or pass on these injection utensils.
Couples one of whom is HIV-positive should avoid an unplanned
pregnancy.
Condom effectiveness http://www.ncbi.nlm.nih.gov/pubmed/1411838

HIV

.
HIV : sperm = 90-160x10-9m: 2.5-3.5x10-6m
Precautions for Healthcare Staff Kayser, Medical Microbiology 2005 Thieme

HIV
All personnel in medical professions should know that
HIV is not highly contagious and that precautions, as
they apply to hepatitis B, are considered sufficient:
Wear protective gloves in all situations involving possible
contact with blood.
If blood droplets could be spattered or sprayed, masks and
goggles should also be worn.
If exposure has occurred despite precautions (accidental
injection, stab wound, contamination of a wound or mucosa
with material containing HIV), immediate commencement of a
combination therapy with one PI and two NRTIs for two to
four weeks is indicated in addition to a thorough wound toilet
and disinfection.
Kesimpulan
Dari pemeriksaan lab, yaitu : ELISA dan
Western Blot (+), maka disimpulkan wanita
muda ini terinfeksi HIV, yang diperkirakan
berasal dari pasangan seksnya

Saran
Melakukan terapi HIV
Mengubah gaya hidup (bergonta-ganti
pasangan seksual dan merokok)
Daftar Pustaka
Henrys Clinical Diagnosis & Management by Laboratory Methods
21st ed. McPherson RA, Pincus MR. Saunders Elsevier:
Philadelphia. 2007. pp 945-960
Cellular and Molecular Immunology 6th ed. Abbas AK, Lichtman AH.
Chapter 20: Congenital & Acquired Immunodeficiencies. Saunders
Elsevier: Philadelphia. 2009. pp.173-197
Harrisons Principles of Internal Medicine 15th ed,
Medical Microbiology. Kayser F, Bienz K, Eckert J, Zinkernagel R.
Part 4: Virology. Chapter 7: General virology. Chapter 8: Viruses as
Human Pathogen. Thieme Stuttgard: New York. 2005
Imunologi dasar. Bratawijaya KG, Rengganis I. 8th ed. Jakarta :
FKUI ; 2009.