Documenti di Didattica
Documenti di Professioni
Documenti di Cultura
HIV/AIDS
(ARV - PPP - PPIA)
1
Tujuan Pembelajaran
1. Mahasiswa dapat menjelaskan gejala klinis
terkait HIV
2. Mahasiswa dapat menjelaskan pemeriksaan
penunjang untuk HIV
3. Mahasiswa dapat menyebutkan antiretroviral
4. Mahasiswa dapat menjelaskan tentang VCT
dan PITC
5. Mahasiswa dapat menjelaskan tentang
pencegahan pasca pajanan
6. Mahasiswa dapat menjelaskan tentang
program pencegahan penularan ibu ke anak 2
Epidemiologi Global
• Estimated 45 million people living with
HIV/AIDS in 2017
• 2.2 million new infections per year
• 15 millions people accessing ARV (March
2015)
• 1.6 million deaths per year
• Parts of Africa 25-40% of adults are
infected
• 85% heterosexual transmission worldwide 3
Karakteristik Virus
• Icosahedral (20 sided),
enveloped virus of the
lentivirus subfamily of
retroviruses.
• Retroviruses transcribe RNA to
DNA.
• Two viral strands of RNA found
in core surrounded by protein
outer coat.
– Outer envelope contains a lipid
matrix within which specific viral
glycoproteins are imbedded.
– These knob-like structures
responsible for binding to target4
cell.
Transmisi HIV
• Blood, semen, breast milk, saliva
(minimum)
• Sexual, parenteral, vertical (mother to
child)
• Risk of contracting infection dependent on
– Viral load
– Integrity of the exposed site
– Type of body fluid
– Volume of body fluid
5
Transmisi HIV
• Risk after a single exposure
– >90% blood or blood products
– 14% vertical
– 0.5-1% injection drug use
– 0.2-0.5% genital mucous membrane
– <0.1% non-genital mucous membrane
6
Transmisi HIV
• Risk of transmission is now 1/10,000,000
with each unit of blood
• 100 confirmed cases from healthcare
exposure
• Risk with needle stick 0.32%
• Risk with mucous membrane exposure
0.03%
7
8
Imunologi HIV
• Gradual reduction in number of circulating
CD4 cells inversely correlated with the
viral load
• Any depletion in numbers of CD4 cells
renders the body susceptible to
opportunistic infections
• Lymphatic tissue (spleen, lymph nodes,
tonsils/adenoids) main reservoir of HIV
9
Serokonversi HIV
• 3-12 weeks, median 8 weeks
• Level of viral load post seroconversion
correlates with risk of progression of
disease
• Differential for this syndrome: EBV, CMV,
Strep pharyngitis, toxoplasmosis,
secondary syphilis
10
11
1. Tanda dan Gejala HIV
12
Infeksi Primer HIV
• 70-80% symptomatic, 3-12 weeks after
exposure
• Fever, rash, cervical lymphadenopathy,
aseptic meningitis, encephalitis, myelitis,
polyneuritis
• Surge in viral RNA copies to >1 million
• Fall in CD4 count to 300-400
• Recovery in 7-14 days
13
Acute Retroviral Syndrome
• Fever 96%
• Lymphadenopathy 74%
• Pharyngitis 70%
• Rash 70%
• Myalgia/Arthraligia 54%
• Diarrhea 32%
• Headaches 32%
• Nausea/Vomiting 27%
• Hepatomegaly 14%
• Weight Loss 13%
• Neurologic symptoms 12%
14
Fase Asimptomatik
• Remain well with no evidence of HIV
disease except for generalized
lymphadenopathy
• Fall of CD4 count by about 50-150 cells
per year
15
Fase Simptomatik
• Mild impairment of immune system
• Chronic weight loss
• Fever
• Diarrhea
• Mild candida infections
• Recurrent herpes infections
• Pelvic inflammatory disease
• Bacillary angiomatosis
• Cervical dysplasia
16
CDC Stage of HIV Disease
• Stage I Acute HIV infection
• Stage II Asymptomatic HIV
• Stage III Early Symptomatic HIV
• Stage IV Late Symptomatic HIV
–A Constitutional Disease
–B Neurological Disease
–C Secondary Infections
• C1 AIDS defining
• C2 Other infections
–D Secondary Cancers
–E Other Conditions
17
18
19
20
AIDS
• CD4 <200
– Pneumocystis pneumonia
– Esophageal Candidiasis
– Mucocutaneous herpes simplex
– Miliary/extrapulmonary TB
– Cryptosporidium
– HIV-associated wasting
– Microsporidium
– Peripheral neuropathy
21
AIDS
• CD <100
– Cerebral toxoplasmosis
– Non-Hodgkin’s lymphoma
– Cryptococcal meningitis
– HIV-associated dementia
– Primary CNS Lymphoma
– Progressive multifocal leukoencephalopathy
22
AIDS
• CD4<50
– CMV retinitis, gastroenteritis
– Disseminated Mycobacterium avium complex
23
Skin and Oral disease
• Seborrheic dermatitis
• Xeroderma
• Itchy folliculitis
• Scabies
• Tinea
• Herpes zoster
• Papillomavirus
• Oral and vaginal candidiasis
• Oral hairy leukoplakia
• Aphthous ulcers
• Herpes simplex
• Gingivitis
• Kaposi’s sarcoma
• Molluscum contagiosum
• Bacillary angiomatosis
24
WHO Clinical Staging of Oral Manifestations
of HIV
Stage Adults and Adolescents (>15 yo) Children < 15 yo
1 No disease No disease
Angular cheilitis Angular Cheilitis
2
Recurrent oral ulceration Linear gingival erythema, extensive warts
Recurrent oral ulcerations, parotid enlarge
4 Chronic (>1 mo) orolabial HSV Chronic (>1 mo) orolabial HSV
Kaposi’s sarcoma Kaposi’s sarcoma
Non-Hodgkin’s lymphoma Non-Hodgkin’s lymphoma
27
Manifestasi Oral
CLINICAL MANIFESTATIONS
2. Pemeriksaan
Laboratorium HIV
29
Pemeriksaan Penunjang HIV
30
2.1 Tes ELISA
• First serological test developed to detect
HIV infection.
– Easy to perform.
– Easily adapted to batch testing.
– Highly sensitive and specific.
• Antibodies detected in ELISA include
those directed against: p24, gp120, gp160
and gp41, detected first in infection and
appear in most individuals
31
2.1 Tes ELISA
• ELISA tests useful for:
– Screening blood products.
– Diagnosing and monitoring patients.
– Determining prevalence of infection.
– Research investigations.
32
2.1 Tes ELISA
• Different types of ELISA techniques used:
– indirect
– competitive
– sandwich
• ELISAs are for screening only, false
positives do occur and may be due to
Autoimun disease, alcoholism, syphilis,
and immunoproliferative diseases.
33
Tes Penapisan lain
• Agglutination tests using latex particles, gelatin
particles or microbeads are coated with HIV
antigen and will agglutinate in the presence of
antibody.
• Dot-Blot Testing utilizes paper or nitrocellulose
impregnated with antigen, patient serum is
filtered through, and anti-antibody is added with
enzyme label, color change is positive.
– A rapid, cost-effective and may become an alternative
to standard ELISA and Western blot testing.
34
Particle Agglutination
35
2.2 Western Blot
• Most popular confirmatory test.
– Utilizes a lysate prepared from HIV virus.
– The lysate is electrophoresed to separate out the HIV
proteins (antigens).
– The paper is cut into strips and reacted with test sera.
– After incubation and washing anti-antibody tagged
with radioisotope or enzyme is added.
– Specific bands form where antibody has reacted with
different antigens.
– Most critical reagent of test is purest quality HIV
antigen.
– The following antigens must be present: p17, p24,
p31, gp41, p51, p55, p66, gp120 and gp160.
36
2.2 Western Blot
• Antibodies to p24 and p55 appear earliest
but decrease or become undetectable.
• Antibodies to gp31, gp41, gp 120, and
gp160 appear later but are present
throughout all stages of the disease.
37
2.2 Western Blot
• Interpretation of results.
– No bands, negative.
– In order to be interpreted as
positive a minimum of 3
bands directed against the
following antigens must be
present: p24, p31, gp41 or
gp120/160.
• CDC criteria require 2
bands of the following: p24,
gp41 or gp120/160.
38
2.2 Western Blot
• Indeterminate results are those samples that produce
bands but not enough to be positive, may be due to the
following:
– prior blood transfusions, even with non-HIV-1 infected blood
– prior or current infection with syphilis
– prior or current infection with malaria
– autoimmune diseases (e.g., diabetes, Grave’s disease, etc)
– infection with other human retroviruses
– second or subsequent pregnancies in women.
– run an alternate HIV confirmatory assay.
• Quality control of Western Blot is critical and requires
testing with strongly positive, weakly positive and
negative controls.
39
2.3 Polymerase Chain Reaction
(PCR)
• Looks for HIV DNA in the WBCs of a person.
• PCR amplifies tiny quantities of the HIV DNA present,
each cycle of PCR results in doubling of the DNA
sequences present.
• The DNA is detected by using radioactive or biotinylated
probes.
• Once DNA is amplified it is placed on nitrocellulose
paper and allowed to react with a radiolabeled probe, a
single stranded DNA fragment unique to HIV, which will
hybridize with the patient’s HIV DNA if present.
• Radioactivity is determined.
40
2.4 Isolasi Virus
• Virus isolation can be used to definitively
diagnose HIV.
• Best sample is peripheral blood, but can use
CSF, saliva, cervical secretions, semen, tears or
material from organ biopsy.
• Cell growth in culture is stimulated, amplifies
number of cells releasing virus.
• Cultures incubated one month, infection
confirmed by detecting reverse transcriptase or
p24 antigen in supernatant.
41
2.5 Tes Viral Load
• Viral load or viral burden is the quantity of HIV-RNA
that is in the blood.
• RNA is the genetic material of HIV that contains
information to make more virus.
• Viral load tests measure the amount of HIV-RNA in one
milliliter of blood.
• Take 2 measurements 2-3 weeks apart to determine
baseline.
• Repeat every 3-6 months in conjunction with CD4 counts to
monitor viral load ant T-cell count.
• Repeat 4-6 weeks after starting or changing
antiretroviral therapy to determine effect on viral 42
load.
2.6 Tes untuk Neonatus
• Difficult due to presence of maternal IgG
antibodies.
• Use tests to detect IgM or IgA antibodies,
IgM lacks sensitivity, IgA more promising.
• Measurement of p24 antigen.
• PCR testing may be helpful but still not
detecting antigen soon enough: 38 days to
6 months to be positive.
43
3. Terapi Antiretroviral
(ARV)
44
45
Siklus Hidup HIV
Ada 5 tahap replikasi HIV
1. Binding and entry (interaksi envelope virus dengan reseptor sel
host, fusi membran envelope, capsid virus masuk dalam sel)
2. Reverse transcription (RNA ditranskripsi menjadi DNA, DNA akan
bermigrasi ke nukleus)
3. Replication (di dalam nukleus, DNA virus yang terbentuk akan
bersatu dengan DNA sel host, enzim integrase mengkatalis
penyatuan DNA virus dengan genom sel host sehingga di dalam
genom sel host terdapat gen hiv → provirus)
4. Budding (virus akan membentuk struktur inti, migrasi ke membran
sel dan memperoleh envelope lipid dari sel host)
5. Maturation (setelah matur akan dilepaskan sebagai partikel virus
yang infeksius dan siap menginfeksi sel lain)
47
Tujuan Terapi arv
Secara klinis :
• mengurangi morbiditas dan mortalitas karena infeksi HIV
• memperbaiki mutu hidup
Secara imunologi :
• memulihkan sistem dan memelihara sistem imun
kekebalan dan mengurangi terjadinya IO
Secara virologi :
• menekan replikasi virus semaksimal mungkin dalam
waktu yang lama dengan menekan viral load
Secara epidemiologi
• mengurangi penularan HIV – treatment is prevention
Obat Antiretroviral
68
VCT
V (Voluntary) mendorong orang untuk datang ke
tempat layanan yang tadinya mereka ingin hindari
Normalisasi dan
destigmatisasi HIV & AIDS Pemberian layanan
kesehatan ibu (ODHA)
Dukungan sebaya, sosial & VCT
masyarakat, termasuk dan layanan
kelompok ODHA
terkait
Pencegahan, penapisan
dan terapi IMS
Akses ke Keluarga
Berencana
Manajemen dini IO
Akses akan kondom
(perempuan dan laki )
• Opt-out • Voluntary
80
Pajanan yang memiliki risiko
penularan infeksi
Perlukaan kulit
Gigitan berdarah
Bahan yang memberi risiko
penularan infeksi
Darah
Cairan bercampur darah yang kasat mata
Cairan yang potensial terinfeksi; semen,
sekret vagina, c.cerebrospinal,c.sinovia,
c.pleura, c.pericardial, c.peritoneal,
c.aminion
Virus yang terkonsentrasi
Status infeksi
Tentukan status infeksi sumber pajanan :
HbsAg positif
HCV positif
HIV positif
Untuk sumber yang tidak diketahui
pertimbangkan risiko ketiga infeksi diatas
Jangan melakukan tes pada jarum bekas
Kerentanan
Tentukan kerentanan orang yang terpajan:
Antibodi HIV
Profilaksis pasca pajanan (PPP)
HBV ; berikan sesegera mungkin, terbaik
24 jam pertama
Belum di vaksinasi 1 dosis HBIG, mulai Beri seri vaksin HBV Beri Vaksin HBV
Vaksin HBV
Pernah divaksinasi
Diketahui sbg responder Tidak perlu pengobatan Tidak perlu pengobatan Tdk perlu pengobatan
Diketahui sbg non 1 dosis HBIG & ulangan Tidak perlu pengobatan Bila diket.sumber paja
responder Seri vaksin HBV nan berisiko tinggi,
obati spt pada HBsAg
positif
Tidak diketahui status Px.Anti-HBs terpajan Tidak perlu pengobatan Px. Anti HBs terpajan
respon antibodinya 1. bila cukup tdk perlu 1. bila cukup tdk perlu
pengobatan pengobatan
2. bila tdk cukup beri 2. bila tdk cukup beri
1 dosis HBIG & boster 1 dosis HBIG&boster
Alur Tatalaksana Pajanan dari pasien terinfeksi HIV
Menentukan Kode Pajanan (KP)
tidak
ya
KP 1 KP 2 KP 2 KP 3
Menentukan Kode status HIV (KS)
Bagaimana status HIV dari sumber pajanan ?
HIV (-)
HIV (+) Tidak diketahui statusnya Tidak diketahui sumbernya
KS
KS 1 KS 2
Tidak tahu
Menentukan Pengobatan Profilaksis Pasca Pajanan
Kategori Pajanan (KP) Kode status/Kadar RNA HIV Anjuran Pengobatan
sumber (KS)
Konseling Pra-tes
Dokumentasi Formal
6. Pencegahan Penularan Ibu
ke Anak (PPIA)
93
Proportion of HIV exposed children
who are infected
• ANTENATAL: 5%
Ante
Post
• DELIVERY: 15%
• POSTNATAL: 10%
Peri
Faktor yang mempengaruhi
penularan
• Faktor Virus:
• Persalinan preterm
(Load,variasi strain)* • Lama ketuban pecah.*
• Maternal: hitung CD4 • Prosedur invasif saat
• Infeksi PMS* persalinan (alat-alat
• Pengguna Narkoba persalinan pervaginam,
• Perilaku seksual* episiotomi*
• Kelainan plasenta • Cara persalinan
• Faktor fetal/neonatal
• Menyusui*
Dapatkah Transmisi Maternal ke Janin/Bayi
dicegah ?
Dapat, bila 1. Terdeteksi
2. Terkendali
- Perilaku
- Obat
- ANC
- Pencegahan Infeksi
3. Pemilihan rute kelahiran
4. Pemilihan ASI/PASI
5. Pemantauan bayi – balita
6. Dukungan dan perhatian
Mechanisms of Mother-Infant HIV Transmission
•Transplacental infection
•Microtransfusion
•"Ascending infection"
•Direct contact by infant
• Turunkan VL serendah-rendahnya
– Pemberian Anti Retro Virus
– Hidup sehat (Tobat)
– Jika suami + Gunakan kondom
Ibu AP IP
bayi
PP
ZDV 2x300 mg/hari po ZDV 300 mg ZDV 2 mg/kg/6 jam
tiap 3 jam Sirup
ASI (-)
Tanpa SC
Ibu AP IP
bayi
PP
ZDV 2x300 mg/hari po ZDV 300 mg ZDV 2 mg/kg/6 jam
tiap 3 jam Sirup
ASI (-)
(+ SC)
Ibu AP IP
bayi
PP
NVP 200 mg NVP 2 mg/kg sirup
po onset ASI (+)
melahirkan
Pemeriksaan fisik
Lab : DPL, SGOT, SGPT, GDS, Ureum,
Kreatinin, VDRL, TPHA, Anti VHC, HbsAg, CD4,
viral load
Asuhan antenatal : Tidak mampu periksa CD4, VL.
Frekuensi sesuai usia kehamilan Kepatuhan diragukan
Konseling : motivasi, pemberian TAR,
coitus
Evaluasi status HIV, PMS, inf.
Oportunistik
TAR: ZDV + 3TC + Nevirapine
mulai usia kehamilan 14 minggu
Evaluasi fungsi hati, CD4, VL setiap 6
bulan
Post Partum :
ZDV oral sirup 2 mg/kgBB/dosis setiap 6 jam selama seminggu mulai saat
usia 8-12 jam. Dosis ZDV iv untuk bayi yang tidak toleransi terhadap
pemberian oral adalah 1,5 mg/kgBB setiap 6 jam ( lihat prosedur bagian
anak)
Monitor status HIV : CD4, VL
Bayi diberikan PASI
Konseling: emosi, alat kontrasepsi, perawatan bayi