Thai Guideline on HIV Diagnosis and Treatment
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Transcript of Thai Guideline on HIV Diagnosis and Treatment
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ISBN 978-974-297-984-3
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National Guidelines on HIV/AIDS Diagnosis and Treatment:
Thailand 2010
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1 (Introduction) 43
2 49
(HIV Laboratory for Diagnastic and Monitoring)
49
2.1 50
2.2 55
2.2.1 55
2.2.2 antibody 57
2.3 68
2.3.1 CD4 68
(CD4 cell counts)
2.3.2 70
(viral load)
2.3.3 72
(HIV drug resistance testing)
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2.4 75
79
3 81
(Management of HIV-Infected Adult)
3.1 81
3.2 94
(acute HIV infection)
3.3 96
(nave)
3.3.1 96
3.3.2 100
3.3.3 103
3.3.4 d4T phase out plan 104
3.4 106
3.5 (drug interaction) 112
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3.6 116
3.7 121
(Immune Reconstitution Inflammatory Syndrome: IRIS)
3.8 130
3.9 133
(adherence to antiretroviral therapy)
3.9.1 adherence 133
3.9.2 adherence 134
3.10 142
(diagnosis and management of treatment failure)
3.10.1 142
3.10.2 144
3.11 149
3.12 166
3.12.1 166
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3.12.2 168
3.12.3 170
3.12.4 172
3.12.5 174
methadone
3.12.6 176
3.13 178
3.14 181
3.15 185
(post-exposure prophylaxis)
3.15.1 185
(HIV Occupational Post-Exposure
Prophylaxis: HIV OCC-PEP)
3.15.2 186
(HIV Sexual Post-exposure
Prophylaxis: HIV SEX-PEP)
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198
4 211
(Management of HIV-Infected Children)
211
4.1 212
4.1.1 212
4.1.2 212
4.1.3 224
4.2 228
(ARV therapy in nave HIV-infected children)
4.2.1 228
4.2.2 230
4.2.3 233
(antiretroviral nave)
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4.2.4 234
NVP
12
4.2.5 235
(antiretroviral therapy in children with
opportunistic infection)
4.3 240
4.4 242
4.5 252
(Immune Reconstitution Inflammatory
Syndrome: IRIS)
4.6 257
(diagnosis of treatment failure in HIV-infected
children)
4.6.1 258
4.6.2 261
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4.7 262
4.7.1 263
genotyping
4.7.2 genotyping PIs 266
4.7.3 267
2NRTIs + 1NNRTI
4.7.4 3 275
NRTIs, NNRTIs PIs
4.7.5 275
NRTIs 2 (dual NRTIs therapy)
4.7.6 276
dual NRTIs
4.7.7 277
4.8 278
4.9 280
4.9.1 280
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4.9.2 280
4.10 281
(adherence to antiretroviral treatment in children)
4.11 283
285
5 293
(Prophylaxis of Mother to Child
Transmission: PMTCT)
293
5.1 295
5.2 299
5.2.1 300
5.2.2 302
5.2.3 303
5.2.4 304
(no ANC)
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5.3 315
5.4 316
HAART
5.5 319
5.5.1 319
5.5.2 319
(elective caesarean section)
5.6 320
5.7 321
324
6 329
(Opportunistic Infection: Prophylaxis and Treatment)
6.1 Candidiasis 330
6.2 Cryptococcosis 334
6.3 Cytomegalovirus (CMV) infection 338
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6.4 Mycobacterium avium complex (MAC) infection 342
6.5 Penicilliosis histoplasmosis 347
6.6 Pneumocystis pneumonia (PCP) 351
6.7 Toxoplasmic encephalitis 357
6.8 Tuberculosis 362
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379
Schematic representation of the UNAIDS and 381
WHO HIV testing strategies
382
(AIDS-defining 383
illnesses CDC classification)
Child-Pugh Score 384
(drug interaction) 385
rapid desensitization 409
TMP-SMX
411
418
421
Creatinine Clearance 432
433
434
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2[1] 76
2[2] 77
2[3] 78
3[1] 95
acute retroviral syndrome
3[2] 98
3[3] 101
3[4a] NRTIs 107
3[4b] NNRTIs 109
3[4c] PIs INSTIs 110
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3[5] 121
3[6] IRIS 125
3[7] 132
3[8a] adherence 137
/
3[8b] adherence 139
/
3[9] 2 147
3[10] 150
3[11] 169
3[12] 171
3[13] PIs 175
methadone
3[14] 179
3[15] 184
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3[16a] HIV OCC-PEP 189
3[16b] HIV OCC-PEP 190
3[16c] HIV OCC-PEP 191
HIV SEX-PEP
3[17] 192
HIV OCC-PEP
3[18] 192
3[19a] HIV SEX-PEP 194
anti-HIV
3[19b] HIV SEX-PEP 195
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3[19c] HIV SEX-PEP 196
3[20] 197
HIV SEX-PEP
4[1a] 215
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4[1b] Hib 217
4[1c] PCV 217
4[2a] 1-6 221
4[2b] 7-18 221
4[3] 232
4[4] 242
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4[5] IRIS 257
4[6a] genotyping NRTIs 265
4[6b] genotyping NNRTIs 266
4[7a] NRTIs 270
4[7b] PIs 271
4[8] 279
%CD4
-
5[5] 318
GCT OGTT
6[1] CD4 primary 371
secondary prophylaxis
6
6[2] CD4 primary 372
secondary prophylaxis
1-
-
[7] PIs 405
[8] 406
NNRTIs, RAL, PIs
[9] rapid desensitization 410
TMP-SMX
[10] 416
CD4
[11] (staging) 417
[12] 421
[13] 433
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2[1] 59
18
2[2] 65
18
2[3] 74
(HIV-1 drug resistance)
3[1] 188
3[2] 193
4[1] IRIS 254
4[2] 261
4[3] 262
4[4] 274
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5[1] 297
5[2] 298
[1] Schematic representation of the UNAIDS 381
and WHO HIV testing strategies
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ABC Abacavir
ATV Atazanavir
AZT Zidovudine
Clar Clarithromycin
CCBs Calcium channel blockers
ddI Didanosine
d4T Stavudine
ddC Zalcitabine
DRV Darunavir
EC Enteric coated
EE Ethinyl estradiol
EFV Efavirenz
ETR Etravirine
FTC Emtricitabine
GCV Ganciclovir
HAART High active antiretroviral therapy
IDV Indinavir
INH Isoniazid
IVIG Intravenous immune globulin
LPV/r Lopinavir/ritonavir
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NNRTI Non-nucleoside reverse transcriptase inhibitor
NRTI Nucleoside reverse transcriptase inhibitor
NVP Nevirapine
PAS Para-aminosalicylic acid
PI Protease inhibitor
PPIs Proton pump inhibitors
PZA Pyrazinamide
/r Ritonavir boosted
RAL Raltegravir
RBT Rifabutin
RTV Ritonavir
SQV Saquinavir
TDF Tenofovir
TMP Trimethoprim
TMP-SMX Trimethoprim/sulfamethoxazole
TPV Tipranavir
3TC Lamivudine
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BCG Bacillus Calmette-Gurin
DTP Diphtherias, tetanus, pertussis vaccine
DT/dT Diphtheria, tetanus vaccine
DTaP/Tdap Diphtherias, tetanus, acellular pertussis vaccine
DTwP Diphtheria, tetanus, whole cell pertussis vaccine
HAV Hepatitis A vaccine
HbOC Polyribose ribital phosphate-outer membrane protein complex
HBV Hepatitis B vaccine
Hib Haemophilus influenza type B vaccine
HPV Human papilloma vaccine
IPV Injection polio vaccine
JE Japanese encephalitis vaccine
MMR Measles, mumps, rubella vaccine
OPV Oral polio vaccine
PCV Pneumococcal conjugate vaccine
PRP-OMP Haemophilus B conjugate vaccine
PRP-T Polyribose ribital phosphate-tetanus toxoid
PS23 23-valent polysaccharide vaccine
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AFB Acid-fast bacilli
AUC Area under the curve
BMI Body mass index
CMV Cytomegalovirus
CO2 Serum bicarbonate
CSF Cerebrospinal fluid
CXR Chest x-ray
EKG Electrocardiography
FBS Fasting blood sugar
GCT Glucose challenge test
GDM Gestational diabetes mellitus
HAART Highly active antiretroviral therapy
HAV Hepatitis A virus
HBV Hepatitis B virus
HCV Hepatitis C virus
Hct Hematocrit
HPV Human papilloma virus
INR International normalised ratio
IRIS Immune reconstitution inflammatory syndrome
KS Kaposi sarcoma
LDL Low-density lipoprotein
MAC Mycobacterium avium complex
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MDR-TB Multi drug resistant TB
OFC Occipito frantal circumference
OGTT Oral glucose tolerance test
OI Opportunistic infection
PCP Pneumocystic pneumonia
PML Progressive multifocol leukoencephalopathy
PMTCT Prevention of mother to child transmission
RBC Red blood cell
RPR Rapid plasma reagin
TAMs Thymidine analog mutations
TB Tuberculosis
TC Total cholesterol
TG Triglyceride
VCT Voluntary counseling and testing
VDRL Venereal disease research laboratory test
VLDL Very low-density lipoprotein
WBC White blood cell
WHO World Health Organization
XDR-TB Extensively drug resistant TB
.
.
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.. 2527
10
(Introduction)
1
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()
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.. 2543-2544
3,000
.. 2543-2544
2 1)
2)
.. 2545
3
Three by Five
(3x5) (WHO)
3 2005
(The Global Fund to Fight AIDS, Tuberculosis and Malaria)
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1
50,000
.. 2545 .. 2547
Vender Managed Inventory
(VMI)
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4 1)
2)
3)
4)
WHO
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Hospital Accreditation (HA),
HIV Quality Thailand (HIVQUAL-T)
2
(HIV laboratory for diagnosis and monitoring)
(Provider-Initiated Counseling and Testing: PICT)
18
antibody
CD4 viral load
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3
(management of HIV-infected adults)
methadone
4
(management of HIV-infected children)
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5
(prevention of mother-to-child transmission)
3
HAART
Glucose Challenge Test (GCT)
6
(opportunistic infections: prophylaxis and treatment)
CD4 primary secondary prophylaxis
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(HIV Laboratory for Diagnostic and Monitoring)
CD4
viral load
2
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2.1
(Voluntary
Counseling and Testing: VCT)
(pre-test / post-test counseling)
(group counseling)
(individual counseling)
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(Provider-Initiated Testing and Counseling: PITC)
(opt-out technique)
51
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1)
2)
- - -
3)
4)
5)
6)
7)
8)
9)
10)
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1)
2
2)
3 (window period)
/ 3
antibody (seroconversion)
3)
1
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2.2
2
antibody
2.2.1
1)
p24 Ag
(core)
p24 Ag
p24 Ag
p24 Ag
antibody 5
5
antibody antibody
(indeterminate)
2) (Nucleic acid
AmplificationTest:NAT)
RNA
(qualitative RNA)*
* (positive or negative)
55
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proviral DNA
antibody
p24 Ag
antibody
18 antibody
(positive)
(negative)
-
-
-
antibody antibody
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2.2.2 antibody
antibody
35 .. 2550
99.5
99.0
antibody
1) (ELISA)
HIV antigen solid phase
antigen antibody
substrate
2) (agglutination)
HIV antigen
(simple test)
3) dotlineimmunoassay
HIV antigen solid phase
(dot) (line)
(rapid test)
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18
antibody
3
(WHO)
Western blot 2[1]
ELISA, simple test rapid test
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2[1]
18
( 5)
(1)
3 (A3)
(Non Reactive) (A1-)
(1)
1 (A1)
(1)
2 (A2)
A1
A2 (A1+, A2-)
A1 A2
A1 A2
(A1-, A2-)
A1
A2
(A1+, A2-)
A1 A2
(A1+, A2+)
(Anti-HIV Positive)(2)
2
A1, A2
A3
(A1+, A2+, A3-)
A1, A2 A3
(A1+, A2+, A3+)
(Anti-HIV Negative)
(3)
(Indeterminate)
(Reactive) (A1+)
A1 A2 (A1+ A2+)
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(1) A1, A2 A3 1, 2 3 antibody
antibody antigen
1 2 3 (2)
(newly diagnosed) 2 antibody
1 (3) (indeterminate) 2
/ 3 6 A1, A2 A3
6
(indeterminate)
antigen antibody
(HIV Ag/Ab) fourth generation
p24 Ag
HIV Ag/Ab
p24 Ag / antibody
antibody anti-HIV 2
p24 Ag
anti-HIV p24 Ag blocking
anti-p24 antibody
HIV Ag/Ab
18
(false positive)
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antibody
3 (A1, A2 A3)
antigen
antigen
A1
(sensitivity) 3 *
A2 A3
(specificity)
simple test
rapid test
* Ag/Ab windows period
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2[1]
1. (anti-HIV negative) antibody
2. (anti-HIV positive) antibody
3
3. (indeterminate)
antibody
2 / 3 6
(indeterminate)
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18
antibody
antibody
12
antibody 95
antibody 12
antibody 18
2[2]
proviral DNA PCR
(dried blood spot)
2-3
1
EDTA 2-3 mL
48
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1:32
CSF RPR neurosyphilis
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-
2
neurosyphilis
3.1.3
1)
latent infection primary tuberculosis
10
(life time risk) 50
5-10
6
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CXR
2) CMVretinitis
CMV
CD4
100 cells/mm3
(sensitivity 7)
indirect ophthalmoscope 1
CD4 100 cells/mm3
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3)
)17
$%
QBQ TNFBS
4)
)17
$%
QBQTNFBS
88
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anal pap smear
6 1
3.1.4
1)
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1.1)
17-30
(11-58 )
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-
-
-
-
-
1.2)
/
91
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-
-
-
3.14
2)
BMI (kg/m2)
17
BMI 18.5 2
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PIs
-
-
- 6
93
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3.2 (acuteHIVinfection)
4090
acute retroviral syndrome 3[1]
infectious
mononucleosis streptococcus syphilis
viral load
( 100,000 copies/mL)
anti-HIV
negative indeterminate qualitative HIV-RNA p24 Ag
viral
set point
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3[1] acute retroviral syndrome
96
74
70
(erythematous maculopapular rash)
70
54
32
32
27
14
13
(thrush) 12
( aseptic meningitis,
peripheral neuropathy, facial palsy,
Guillain-Barr Syndrome, brachial neuritis
cognitive impairment) 12
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3.3 (nave)
3.3.1
1)
CD4 viral load
2)
CD4
..2549/2550 3[2]
3) viral load
CD4
(AIDS-related
illness)
CBC, CD4,
viral load (), FBS, AST, ALT, lipid
profile (TC, TG, LDL), HBsAg, anti-HCV, VDRL, urine
analysis, CXR, pap smear
TDF IDV
96
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3
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-
serum creatinine creatinine
clearance ABC
HLA-B*5701
hypersensitivity
fundoscopy (eye ground)
CD4 100 cells/mm3
CMV retinitis
IRIS
97
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3
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-
CD4
(cells/mm3)
(AIDS-defining illness)*
**
350
>350
CD4 6
CD4 >350 cells/mm3
3[2]
* (AIDS-defining illness)
**
(Pruritic Papular Eruptions: PPE)
14 10 3
herpes zoster 2 dermatomes
98
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-
CD4350cells/mm3(specialconsiderationforART
initiation)
1) HBV HCV
HBV HCV
3.12.4
2) 50 (CD4
>350-500 cells/mm3)
3) discordant couples, HIV-associated
nephropathy
99
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3
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-
3.3.2
5
1) Nucleoside or nucleotide reverse transcriptase inhibitors
(NRTIs or NtRTI) zidovudine (AZT), stavudine (d4T), lamivudine (3TC),
emtricitabine (FTC), didanosine (ddI), abacavir (ABC), tenofovir (TDF)
fixed-dose combination AZT/3TC 300/150 mg,
d4T/3TC 30/150 mg, TDF/FTC 300/200 mg (FTC fixed-dose
combination TDF )
2) Non-nucleoside reverse transcriptase inhibitors (NNRTIs)
nevirapine (NVP), efavirenz (EFV), etravirine (ETR) NVP
fixed-dose combination NRTIs d4T/3TC/NVP 30/150/
200 mg AZT/3TC/NVP 250/150/200 mg
3) Protease inhibitors (PIs) indinavir (IDV), ritonavir
(RTV), nelfinavir (NFV), saquinavir (SQV), lopinavir/ritonavir (LPV/r),
atazanavir (ATV), darunavir (DRV)
4) Integrase inhibitors (INSTIs) raltegravir (RAL)
5) Fusion inhibitors (FIs) enfuvirtide (ENF)
NNRTIs-based regimen NNRTIs
PIs-based regimen
.. 2549/2550
3[3]
100
.. 2553
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-
NRTIs
+
NNRTIs
NNRTIs
PIs
Preferred
EFV(6)
NVP(7)
Preferred
AZT + 3TC(1)
TDF + 3TC/FTC(2)
LPV/r(8)
Alternative Alternative
ABC + 3TC(3)
d4T + 3TC(4)
ddI + 3TC(5)
ATV/r
DRV/r(9)
SQV/r
3[3]
101
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3
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-
3[3]
(1) AZT + 3TC NRTIs (2) TDF NtRTIs
creatinine clearance
HBV TDF + 3TC/FTC (3) ABC + 3TC NRTIs
AZT, d4T, ddI TDF ABC
hypersensitivity reaction NVP ABC
NVP(4) d4T + 3TC NRTIs d4T
AZT, TDF 6-12
d4T (5) ddI + 3TC AZT, d4T TDF
(6) EFV NNRTI
NVP EFV
(7) NVP NNRTI
AZT + 3TC
CD4 250 cells/mm3
(8) LPV/r PI
nave 800/200 mg 24 . 400/100 mg 12 .(9) DRV/r nave 800/100 mg 24 .
IDV, IDV/r
IDV/r 400/100 mg 12 .
102
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-
3.3.3
NRTIs
2
d4T + AZT antagonism
FTC + 3TC resistance profiles
TDF + ddI
d4T + ddI peripheral neuropathy,
pancreatitis, hyperlactatemia lactic acidosis
2
TDF + 3TC + ABC
EFV
2NNRTIs combination
unboosted SQV, DRV
ATV + IDV hyperbilirubinemia
103
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3
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-
3.3.4 d4Tphaseoutplan
d4T NRTIs 15
generic
d4T, 3TC NVP (
GPO-VIR S)
d4T lipoatrophy/
lipodystrophy, peripheral neuropathy, hyperlipidemia treatment
guidelines d4T list preferred ARV
regimen WHO d4T
d4T
d4T
d4T
d4T
d4T
104
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-
d4T
1) d4T GPO
-VIR S lipoatrophy/
lipodystrophy
viral load
50 copies/mL GPO-VIR S
TDF + 3TC + NVP TDF + 3TC + EFV
2) d4T GPO
-VIR S lipoatrophy/lipodystrophy
GPO-VIR Z viral load
50 copies/mL 12
viral load 50 copies/mL
GPO-VIR S
..2554 AZT
lipoatrophy/lipodystrophy GPO-VIR Z
6 TDF + 3TC + NVP TDF + 3TC
+ EFV
3) d4T GPO-VIR S
d4T 30 mg 60 kg
d4T
105
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3
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-
(nave)
GPO-VIR S (Hb
-
3[4a]
N
RTI
s
3TC
300
mg
24
.
15
0 m
g
12
.
CrC
l (m
L/m
in)
30-4
9 15
0 m
g
24
.
15-2
915
0 m
g
100
mg
24
.
5-14
150
mg
50
mg
24
.
6
AZT
200-
300
mg
12
.
(CrC
l 38.6 C), increasing respiratory symptoms, increasing lymphadenopathy, cutaneous lesions, ascites, CXR worsening] after initiation of HAART, tuberculoma, inflammatory bowel perforation, serositis, psoas abscess
MAC and other atypical mycobacteria
Localized lymphadenitis, necrotizing subcuta-neous nodules, endobronchial tumors, small bowel involvement, paravertebral abscesses, osteomyelitis, arthritis, focal brain lesion, Ileitis
CMV CMV retinitis despite rise in CD4 cells after initiation of HAART, immune recovery vitreitis, immune recovery uveitis, early and unusual CMV pneumonitis, pseudotumoral colitis, adenitis, encephalitis, cutaneous ulceration
Viral hepatitis (B,C) Worsening hepatitis
Parvovirus B19 Encephalitis, worsening anemia
Herpes simplex Erosive herpes simplex, encephalitis
Varicella zoster virus Acute retinal necrosis early after effective HAART regimen, increase rate of shingles after HAART
Kaposi Sarcoma (KS) Worsening KS lesion with inflammation and edema
PML Inflammatory PML variant
BK virus Hemorrhagic cystitis
3[6] IRIS
125
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3
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-
Cryptococcus Recurrence of meningitis early after effective HAART, pulmonary cryptococcosis, cutaneous cryptococcosis (recurrent abscesses), necrotizing mediastinal and cervical lymphadenitis, intracranial cryptococcoma, intramedullary abscess, necro-tizing pneumonitis
PCP Pneumonitis (patchy aveolar or reticulonodular infiltrates)
Skin yeasts Folliculitis
Sarcoidosis Worsening of sarcoidosis, pulmonary infiltrates, erythrema nodosum, lymphadenopathy, inter-stitial nephritis
Toxoplasmosis Encephalitis
Leshmaniasis Vitreitis, uveitis, post-Kala-Azar dermal leshmaniasis
Bartonella henselae Granulomatous splenitis
Leprosy Leprosy cutaneous lesions
Microsporidia Keratoconjunctivitis
Chlamydia trachomatis Reiters syndrome
Non infectious etiology Grave diseases, SLE, vasculitis, relapsing Guillain-Barrs syndrome, rheumatoid arthritis, polymyositis, alopecia universalis, cerebral vasculitis, hyperergic reaction (against tatoos, foreign bodies), pre-eclampsia, multiple eruptive dermatofibromas, eruptive cheilitis, peyronies disease
126
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-
IRIS
IRIS
cryptococcus MAC
1) IRIS paradoxical
worsening
CD4 100 cells/mm3
2-4
unmasking
corticosteroids
MDR-TB, MAC
corticos-
teroids prednisolone 30 mg/day
24-48 .
IRIS
rifampicin
IRIS prednisolone
8
IRIS
127
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3
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-
2) Cryptococcal meningitis IRIS
30 paradoxical worsening
localizing signs
Cryptococcal meningitis unmasking
meningitis
cryptococcal antigen
paradoxical worsening
cryptococcal meningitis
cryptococcal meningitis
6
cryptococcal
antigen india ink cryptococcal
antigen cryptococcus india ink
meningitis
cryptococcal meningitis
128
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3
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-
IRIS
prednisolone
lumbar puncture shunt
prednisolone
30-60 mg
prednisolone
3) Mycobacterium avium complex IRIS unmasking
MAC wasting,
chronic diarrhea, lymphadenitis non-caseating granuloma
necrosis
MAC
peritonitis
MAC
129
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3
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-
prednisolone 30 mg/day
prednisolone
3.8
viral load CD4 viral
load CD4
viral load 50 copies/mL
6 viral load 50 copies/mL
viral load
CD4
130
.. 2553
3
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-
CD4
clinical failure
viral load 6
1
1
viral load
. .
CD4
CD4
CD4
(OI prophylaxis)
CD4 6
CD4 100-150 cells/
CD4
CD4
CD4 25
50
CD4 viral load
50 copies/mL
131
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3
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-
* AST statin 6 12
6 rhabdomyolysis
** creatinine clearance
3[7]
CBC, CD4 6, 12 6
Viral load -
6, 12 12
( 6
)
-
3
6
12 -
FBS 6, 12 6 -
ALT* 6, 12 6 3
NNRTIs
Cr** 6, 12 6 6
TDF IDV
Lipid profile
(TC, TG, LDL, HDL)
6, 12 6 -
Urinalysis - - 6
TDF IDV
CXR - -
Pap smear 12 12
132
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-
3.9 (adherencetoantiretroviraltherapy)
3.9.1 adherence
1) multidisciplinary team
2)
3)
adherence
4) adherence
5)
()
6)
7) adherence
133
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3
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-
8) non-adherence
non-adherence
non-adherence
3.9.2 adherence
adherence 2
3[8a]
3[8b]
adherence
adherence 1
adherence
adherence
visual analogue scale, self report,
adherence
134
.. 2553
3
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-
adherence
30
%adherence
dose
dose
%adherence =
adherence
adherence
adherence
1
adherence
135
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3
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-
adherence (
)
2 adherence
fixed dose combination
adherence
adherence adherence
adherence
136
.. 2553
3
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-
1.
(vira
l loa
d as
say)
g
old
stan
dard
a
dher
ence
vira
l loa
d
v
iral lo
ad
a
dher
ence
adhe
renc
e
vira
l load
(u
ndet
ec-
tabl
e leve
l)
2.
(ther
apeu
tic d
rug
mon
itorin
g)
/
a
dher
ence
12
3[8a]
a
dher
ence
/
137
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3
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-
3.
(DO
T)
adhe
renc
e
138
.. 2553
3
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-
1.
(self r
epor
t)
2.
(pill
coun
ts)
a
dher
ence
(p
ill du
mpi
ng)
7
7
p
ill du
mpi
ng
3.
(pill
taking
rec
ord)
/
3[8b]
a
dher
ence
/
139
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3
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-
4.
(pha
rmac
y re
fill r
ecor
ds)
a
dher
ence
(p
ill du
mpi
ng)
5.
(elect
ronic
drug
mon
itorin
g)
M
EMS (m
edicat
ion
even
ts m
onito
ring
syst
em) c
aps
140
.. 2553
3
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-
6.
(follo
w u
p ap
pointm
ent)
7.Visua
lana
logu
esc
ale
s
elf re
port
M
EMS (m
edicat
ion
even
ts m
onito
ring
syst
em) c
aps
8.
(pro
vide
r es
timat
ion)
adhe
renc
e
141
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3
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-
3.10 (diagnosisandmanagementoftreatmentfailure)
3.10.1
(virological failure) virological failure
virological failure
viral load
viral load
400 copies/mL 6
viral load 50 copies/mL
12 viral load
50 copies/mL viral load 50 copies/mL
6
viral load 50 copies/mL viral load
51-1,000 copies/mL
(viral blip)
genotypic resistance testing
142
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3
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-
viral load 2,000 copies/mL*
(immunologicalfailure)
CD4
viral load 50 copies/mL
viral load
Immunological failure CD4
CD4
CD4 50 cells/mm3
1 CD4 30
%CD4 3 CD4
* viral load genotyping
143
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3
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-
(clinicalfailure)
clinical failure virological
failure immunological failure
IRIS 3
3.10.2
144
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-
1)
2)
3) adherence
4) (genotypic resistance testing)
2
5) viral
load (viral load
-
2)
3)
3
3 2
viral load 3
4) NNRTIs
NNRTIs NVP
EFV 2 boosted PIs (boosted PI-based
regimens)
4.1) boosted PIs LPV/r NRTIs
2
4.2) NRTIs 1 LPV/r
NRTIs 1
3TC
4.3) NRTIs
146
.. 2553
3
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-
5) PIs
NRTIs PIs ( boosted)
boosted PIs new boosted PIs NRTIs
/ NNRTIs 2
3[9]
2
2NRTIs + NNRTI Boosted PI + 2NRTIs
()
2NRTIs + PI 1) New boosted PI + 2NRTIs
()
2) New boosted PI + 1NNRTI + 1NRTI
()
3) NNRTI + 2NRTIs
()
3
NRTIs 2
NNRTIs
monotherapy duo-
therapy
3[9] 2
147
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3
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-
1) 3
viral load 50 copies/mL
2)
3)
2
CD4
4)
NRTIs, NNRTIs, PIs boosted PIs
DRV/r
ETR (NNRTIs ) RAL ( INSTIs)
5)
3TC +/- NRTIs viral load
3TC CD4
148
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-
3.11
3
1) (life-threatening adverse effects)
2) (serious adverse effects)
3) (long-term complications)
149
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3
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-
/
1)
(l
ife-thr
eate
ning
adv
erse
effe
cts)
Ste
vens-
Johnso
n
Syn
drom
e (S
JS)
Toxic
E
pid
erm
al
Nec
rolysis
(TEN
)
NVP
0.3
-1%
,
DLV
EFV
0.1
%,
ETR 250
cells/m
m3
0
.9%
C
D4
250
cells/
mm
3
6
.3%
C
D4 >
400
cells
/mm
3
2.3%
C
D4
400
cells/m
m3
1
-3
1
8
fulm
inan
t hep
atic fa
ilure
e
ncep
halo
path
y
50%
DRES
S s
yndr
ome
C
D4
(>25
0 ce
lls/m
m3
, >
400
cells
/
mm
3
)
A
ST
ALT
H
BV
/
HCV
NVP
C
D4
>250 cells
/mm
3
C
D4
>400 cells
/mm
3
NVP
2
NVP
A
ST
ALT
2
1
3
6
(
3TC
,
FTC
T
DF
H
BV
)
s
uppor
tive
care
N
VP
N
NR
TIs
EFV
NVP
151
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3
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-
/
Lacti
c
acid
osis
,
hepa
tic s
teat
osis +
/-
panc
reat
itis
(sev
ere
mito
chon
dria
l to
xici
-
ties)
N
RTI
s
d4T
ddI
A
ZT
0.85
%
50%
(
s
erum
lact
ate
>10
mm
ole/
L)
nons
pecific
gas
trointe
stinal
prod
rom
e
N
RT
I
d
4T
ddI,
AZT
BM
I
d4T
d
dI
ddI
hydro
xyur
ea
ribav
irin
d4T
ddI
d
4T
ddI
lact
ate
CO
2
anio
n ga
p
s
uppor
tive
care
IV
fluid
IV
bicar
bona
te,
hem
odia
lysis
/
hem
ofil
trati
on,
pare
nter
al n
utri-
tion
m
echa
ni-
cal v
entilat
ion
IV t
hiam
ine
/
ri
bofla
vin
seru
m
lact
ate
seru
m la
ctat
e
lact
ate
152
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-
/
:
La
ctat
e
(
>5
mm
ole/
L)
Arter
ial
pH
(
-
/
Lacti
c
acid
osis
,
rapid
ly p
rogr
essi
ve
asce
nding
neur
omus
-
cular w
eakn
ess
d
4T
a
scen
ding
dem
yelin
ating
polyn
euro
path
y
G
uilla
in-B
arr
syn
drom
e
:
Ser
um la
ctat
e, a
nion
gap
Ar
teria
l pH, s
erum
CO
2
Cre
atine
phos
phok
inas
e
d4T
88%
69
d4T
supp
ortiv
e ca
re
lact
ic a
cido
sis
pla
smap
her
esis
,
high
dos
e co
rtico
s-
tero
id,
intrav
enou
s
imm
unoglo
bulin
,
carn
itine
ace
tylcar
-
nitin
e
d4T
154
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-
/
Hyp
ers
ensit
ivit
y
reac
tion
(HSR)
ABC
8%
2
-9%
9
9
0%
6
A
BC
ABC
.
ana
phy-
laxis
H
LA-B
*570
1,
HLA
-DR7,
HLA
-DQ
3
H
SR g
rade
3
4
AB
C 6
00 m
g
24
.
300
mg
12
.
(5%
2%
)
HL
A-
B*5
701
scre
ening
A
BC
HS
R
A
BC
A
BC
vir
al
synd
rom
es
ABC
48
.
su
p-
porti
ve c
are
IV
fluid
ABC
H
SR
ABC
HLA
-B*5
70
1
scre
enin
g
H
SR
ABC
A
BC
155
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-
/
2)
(ser
ious
adv
erse
effe
cts)
Skin
rash
N
VP
14.8
% (
1.5%
),
EFV
26%
(
grad
es 3
-4 1
%),
ABC
250
cell/m
m3
C
D4
>40
0 ce
ll/
mm
3
AST,
ALT
3-4
AST,
ALT
A
LT>5-1
0
AST,
ALT
158
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-
/
Nep
hro
lith
iasis
,
urolith
iasis,
cry
stalluria
ID
V
12.4
%
4
.7-3
4.4%
AT
V
p
yuria
, he
mat
uria
,
crys
tallu
ria
seru
m
crea
tinine
neph
rolithias
is
p
eak
IDV
IDV
1.5-
2
ur
inal
ysis
seru
m cre
atini
ne
3-6
IV
fluid
ID
V
Nep
hrot
oxicity
ID
V
TD
F
IDV
T
DF
n
ephr
o-
geni
c dia
bet
es i
nsip
idus
F
anco
ni s
yn-
drom
e
IDV
TDF
TDF
C
D4
IDV
ser
um
crea
tinine,
urin
alys
is,
seru
m p
otas
sium
phos
phor
us
s
uppor
tive
care
elect
rolyte
s
159
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3
79465_149-210_M4.indd 159 13/11/2553 19:32
-
/
:
ID
V:
Cr
,
p
yrur
ia,
hydro
nephr
osis
ren
al
atro
phy
TD
F: C
r ,
p
rote
inur
ia,
gly
cosu
ria,
hyp
oka
lem
ia,
hy
po
ph
os
ph
ate
mia
, no
n-an
ion
gap,
met
abol
ic
acid
osis
Pan
crea
titis
1-7
%
ddI
4
-5
ddI
hydr
oxyu
rea
ddI
riba
virin
d
dI
d
4T
3
TC,
d4T
TD
F
Am
ylas
e
lip
ase
in
trace
llular
/
ser
um d
dI
panc
reat
itis
hy
per
tri
glyc
erid
emia
ddI
d4T
, hy
dro
xyur
ea,
ribav
irin
ddI
TD
F
dd
I
dd
I
p
ancr
eatit
is
dd
I
d4T
, hyd
rox-
yure
a, rib
avirin
ddI
TDF
amy-
lase
lipa
se
hype
r-tri
glyc
erid
emia
panc
reat
itis
bow
el
rest
, IV
hyd
ration,
pai
n co
ntro
l, pa
rent
eral
nutri
tion
160
.. 2553
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-
/
Ble
edin
g ep
isod
es-
incr
ease
in
he
mo-
philia
c pa
tient
s
P
Is
2-
3
PIs
hem
ophilia
NN
RT
I-b
ased
regi
men
Fact
or V
III
3)
(l
ong-
term
adv
erse
effe
cts)
Lipo
dyst
roph
y
Lip
ohyp
ertr
ophy
PI
NN
RT
I-b
as
ed
regim
ens d
4T
AZT
Li
poat
rophy
NRTI
s
d4T
A
ZT,
ddI
EFV
Lipo
hype
rtrop
hy
(dor
soce
rvical fat
pad
buffa
lo h
ump)
Lipo
atro
phy
b
aseline
BM
I
lipoa
trop
hy
injec
ta-
ble
pol
y-L-
lact
ic
acid
lipoh
yper
tro-
phy
re
stor
ative
lipoh
yper
trop
hy
recom
-bin
ant
hum
an
grow
th h
orm
one
GH-relea
s-in
g
horm
one
anal
ogue
LPV/
r
A
TV/r
vi
s-ce
ral f
at
161
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3
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-
/
Hyp
erlip
idem
ia
P
Is
(
unb
oost
-
ed A
TV)
4
7-75
%
d4T>
AZT
, EF
V>NVP
PIs
LDL,
TC
T
G
HDL
ATV
,
DRV,
LPV,
SQ
V b
oost
ing
RTV
d
4T
TG
LDL
TC
E
FV, N
VP
LD
L, T
C,
TG
HDL
E
FV
NVP
hy
perli
pi-
dem
ia
-P
Is: R
TV-b
oost
ed
PIs
ATV
/r
LDL,
TG
-N
NRTI
s:
PIs, EF
V>NVP
-N
RTIs
: d4T>
AZT
>ABC>T
DF
PIs
NNRTI
s
d4T
fa
sting
li-
pid
profi
le
3-6
c
ardiac
risk
fact
ors
lifes
tyle
mod
ifica
tions
hy
-
perlipi
dem
ia
N
atio
nal
Cho
lest
erol
Edu
-
catio
n Pro
gra
m
ATP III
guid
elines
162
.. 2553
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-
/
Insu
lin re
sist
ance
/
diab
etes
mellitus
d4T,
AZT
PIs
3
-5%
p
olyu
ria,
polydi
psia
,
polyph
agia, fat
igue
hyper
gly
cem
ia
FB
S
1-3
3-6
d
4T,
AZT
N
NRTI
- ba
sed
regi
men
s
met
form
in,
glita
zone
s,
sulfo
nylure
a
insu
lin
Per
iphe
ral n
euro
path
y
dd
I 12
-34%
,
d4T
5
2%
m
onot
hera
py
neur
opat
hy
p
erip
hera
l
neur
opat
hy
a
dvan
ced
HIV
disea
se
d4T
d
dI
163
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3
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-
/
painfu
l neu
ropa
thy
int
race
llula
r ac
tiviti
es
ddI
TD
F,
hydr
oxyu
rea,
ribav
irin
gaba
pent
in, t
ricyc
lic
antid
epre
ssan
ts,
lam
otrig
ine,
oxyc
arba
maz
epin
e,
topi
ram
ate,
tram
adol,
na
rcot
ic a
nalg
esics,
caps
aicin
crea
m,
topi
cal l
idoc
aine
Ost
eone
cros
is
o
ld P
Is
HIV
s
ympt
o-m
atic
ost
eone
cros
is
0.0
8-1
.33%
as
ympto
mat
ic
ost
eonec
rosi
s 4%
M
RI
peria
rticul
ar p
ain
85%
fem
oral h
ead
a
dvan
ced
AID
S
s
tero
ids
hy
perlipi
dem
ia
st
eroi
d
15
%
bony
head
MRI
3-
6
1
6
1
C
onse
rvative
m
anag
emen
t:
Sur
gica
linte
rven
tion:
-E
arly
st
ages
c
ore
deco
m-
pres
sion
/
bo
ne g
rafti
ng
164
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-
/
-S
ever
e
de
bil
ita
tin
g di
seas
e
to
tal
joint ar
thro
plas
ty
Car
diov
ascu
lar
effec
ts, includ
ing
myo
card
ial
infa
rctio
n
(MI),
cer
ebro
vasc
ular
accide
nts
(CVA
)
M
I
CVA
P
Is
M
I
A
BC
ddI
o
bser
vatio
nal
stud
ies
rand
omized
stu
dies
M
I
0
.3-0
.6%
C
VA
0.1
%
co
rona
ry
arte
ry d
isea
se
cere
brov
ascu
lar ac
cide
nts
c
ardi
ovas
-
cula
r dis
ease
h
yper
lipid
emia
c
oron
ary
arte
ry d
isea
se
p
rem
atur
e
coro
nary
art
ery
dise
ase
c
ardi
ac
risk
fact
ors
hype
rlipi
dem
ia
hype
rglyce
mia
lifes
tyle
mod
ifica
tion
h
yper
lipid
emia,
hyp
ert
en
sio
n,
insu
lin r
esista
nce/
diab
etes
mellitus
c
ardi
ac
risk
fact
ors
lif
esty
le
mod
ifica
tions
c
ardi
ovas
-
cula
r eff
ects
N
NR
TI
ATV-
base
d re
gim
en
d4T
165
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3.12
3.12.1
2
(AIDS-defining neoplasms) Kaposis
sarcoma Burkitts immunoblastic
2 2
non-Hodgkins
(primary central nervous system lymphoma)
invasive
CD4 2
Hodgkins
primary effusion lymphoma, plasmablastic lymphoma
basal cell carcinoma seminoma
Hodgkins leiomyosarcoma
166
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-
CD4 viral load
Kaposis sarcoma Burkitts immunoblastic
2
invasive
Hodgkin's non-small cell
CD4
CD4
200 cells/mm3
CD4 200 cells/mm3
167
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3
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-
3.12.2
3[11]
AZT peripheral neuropathy
d4T ddI
HBV,
HCV
168
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-
vira
l loa
d
2
-3
(ele
ctiv
e)
N
NRTI
N
NRTI
s 7-
10
NRTI
s
N
NRTI
s
b
oost
ed P
Is 7
-10
P
Is
3[1
1]
169
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3
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-
3.12.3
TDF, 3TC, EFV
3[12] TDF viral load 50
copies/mL HBV (HBsAg)
EFV
1-2
170
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-
EFV
EFV
NVP
N
VP 4
00 m
g
24
.
LPV/
r
LPV/
r
12
.
24
.
A
TV/r
IDV/
r
L
PV/
r
24
.
A
TV/r
TDF
TDF
ddI
ddI
1
.
2
.
AZT
d4T
A
ZT
d
4T
12
.
T
DF
24
.
vira
l load
12-59
Booster 12-18 2
4[1b] Hib(7)
217
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4
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-
(1) BCG
(2) HBV
DTP-HBV 2, 4, 6
(3) DTP DTwP DTaP (Tdap)
1
(4) Polio vaccine IPV OPV IPV
(5) MMR (clinical stage C %CD4
15) MMR2 1 MMR1
4-6
(6) JE 1 3 4-5
(7) Hib 2
1 12-18
2
4[1b]
218
.. 2553
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-
(8) HAV 1 2
6-12
(9) VAR 1 %CD4 15 2
3
(10) Influenza vaccine
9 2
1
(11) PCV 2 3 2
12-15 4[1c]
PS23 2 PCV
2 PS23 1 5
(12) HPV 3 0, 1-2, 6 9
26
219
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4
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-
4[2a]
4[2b]
6
%CD4 15
220
.. 2553
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-
1 0 dT1, OPV/IPV1, MMR, BCG
2 1 HBV1, JE1
3 2 dT2, JE2, OPV/IPV2, HBV2
4 7 HBV3
5 12 dT3, OPV/IPV3, JE3
1 0 DTP1, OPV/IPV1, Measles/MMR, BCG
2 1 HBV1, JE1
3 2 DTP2, OPV/IPV2, JE2
4 4 DTP3, OPV/IPV3, HBV2
5 8 HBV3
6 12 DTP4, OPV/IPV4, JE3
4[2a] 1-6
4[2b] 7-18
221
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-
PCP
PCP
2-3 (
)
PCP CD4
co-trimoxazole (TMP-SMX) 150 mg/m2
TMP 1-2 3
TMP-SMX
46 PCP
6
12
12
12 %CD4 15
TMP-SMX dapsone
2 mg/kg ( 100 mg) 4 mg/kg ( 200
mg) desensitization
TMP-SMX
222
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-
PPD skin test
223
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-
4.1.3
PCP
224
.. 2553
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-
PCR 1-2
1
PCR1-2
PCR2
PCR1-2
42
anti-HIVPCR
18anti-HIV
anti-HIV12
5-10antibody
anti-HIV
12
anti-HIV18
antibody antigen
(HIV Ag/Ab)
antibody 18
PCR
225
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-
antibody18
antibody
antibodyantibody24
(definitive exclusion of
HIV infection)
1) PCR2
1
4
2) anti-HIV6
2
3) PCR 1 4
anti-HIV16
CD4
226
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-
(presumptive exclusion
of HIV infection)
1) PCR2
14
1
2) PCR1
2
3) anti-HIV 6
1
CD4
227
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4.2 (ARV therapy in nave HIV-infected children)
4.2.1
1) (medicalevaluation)
1.1)
IRIS
latentTBinfection
1.2) CD4
228
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-
TMP-SMX
TMP-SMX
1.3)
CBC,ALT,AST,CD4CD4
CD4 viral load
CXRPPDskin test
PPD
skin test
HBsAg
2)
(ARV counseling)
2.1)
229
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2.2) ( 6)
2.3)
2.4)
3)
(adherence counseling)
4.10
4.2.2
1)
230
..2553
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-
(symptomatic)
1
1
1
CD4
2)
2
2.1) CDCclassificationsystem..2537
categoryA,BC
CDCcategoryBC
2.2) WHOstagingsystem..
2549WHOstage1,2,34
WHOstage34
WHOstage12720
3) CD4 %CD4HIVprognostic
markercollaborative
4,000
2,500CD4%CD4
CD4%CD44[3]
231
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-
- CD4%CD4CD4%CD4
CD4
-
CD4 %CD4
CD4
%CD4
< 1 1- 5 > 5
CDC
categoryB,C
WHO
stage3,4
CDCcategoryB,C
WHOstage3,4
CD4
%CD4
CD4
CD4
%CD425 CD4350cells/mm3
4[3]
1(12-monthmortalityrisk)
CD4%CD4
CD4%CD4
CD4%CD46
232
..2553
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-
NRTIs AZT + 3TC d4T + 3TC
AZT+3TCd4T+3TC
lipodystrophy
(Hb 3
(preferred regimens)
AZT+3TC+NVP AZT+3TC+EFV
(alternative regimens)
d4T+3TC+NVP AZT+3TC+NVP
d4T+3TC+EFV
d4T+3TC+NVP
4.2.3 (antitretroviral nave)
233
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-
NVP
d4T+3TC+NVP(GPO-VIRS)AZT+3TC+NVP
(GPO-VIRZ250)
15hypersensitivity
4.2.4 NVP 12
NVP
NNRTIs 20-57
2NRTIs+PI
NVPNVPEFV
NNRTIsNVP
2NRTIs + PI
(preferred regimens)
AZT+3TC+LPV/r
(alternative regimens)
d4T+3TC+LPV/r
NNRTI NVP EFV
EFV 3 EFV
234
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-
NNRTIs2NRTIs+LPV/r
12viralloadLPV/r
NNRTIs viral load 6
LPV/r
NVP
1
2NRTIs+PI2NRTIs+NNRTI
2NRTIs+NNRTIviral
load6viralload
PI
4.2.5 (antiretroviral therapy in children with opportunistic infection)
IRISCD4
CD4
IRIS20
235
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2
TB,MAC,PCP,cryptococcosis
cryptosporidiosis,microsporidiosis
2-8
8
(CD4)
236
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-
Rifampicin
NNRTIs PIs
PIs
NNRTIs
CXR PPD skin test
supporting evidence
INH
10mg/kg/day9PPDskintest
1) CD4
2) CD4
2-8
IRIS
CD4 CD4
237
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-
1) NNRTIs
(rifampicin)EFVEFV
25
EFVEFV3
EFVNVP
2) NNRTIs PIs
2.1)
rifampicin quinolones
aminoglycosidePIs
2.2)
rifampicin2
maintenance
rifampicin PIs
PIs rifampicin
2(rifampicin
)
3) NNRTIs
tripleNRTIsAZTd4T+3TC+ABC
rifampicin
NNRTIs
PIsABC
238
..2553
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-
NNRTIs
NVP
PIs
PIsPIs
2 (induction period)
PIs maintenance rifampicin
rifampicin
quinolones aminoglycoside
PIs
239
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-
4.3
4.3.1
2-3
2-3
1) (newclinicalevents)
IRIS
2)
(secondarysexcharacteristics)
3) (neurodevelopment)
(OFC) 2
4.3.2
1) (safetymonitoring)
1.1) CBC6AZT
3
WBC
240
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1.2) Chemistryliverenzyme,renalfunction,
lipidprofile6
NVPALT2-4
IDVTDF
urineanalysis(IDVWBC,RBC
TDFglucosuria,proteinuria)creatinine
2-3
2) (immunological and virological
monitoring)
2.1) CD4%CD4
6
2.2) viral load
6
viral load 6 1
CD4 %CD4
viralload
241
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-
1)
Mito
chon
dria
l dys
func
tion
Lacticacido
sis
N
RTIs
d4T
,dd
I
4
1-20
:
:
:
metab
olic
acidos
is
anion
ga
p>1
6
se
rumla
ctate>5
mmol/L
routine
serumla
ctate
bicarbo
nate
thiam
ine,
ribofl
avin,oralantioxida
nt
(L-carnitin
e,coe
nzym
eQ,
vitaminC
)
NRTIs
TDF
ABC
AZT
3TC
se
rumla
ctate
fluo
ride-ox
alate
tube
la
b
4
.
4[4
]
4.4
242
..2553
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-
Pan
crea
titis
N
RTIs
ddI,
d4T
3TC
Serum
amylas
e
lipas
e
routine
serumamylas
e
lipas
e
se
rum
amylas
e
NRTIs
panc
reatitis
AZT
ABC
ddI
d4T
Periphe
ral
neurop
athy
d4T,ddI
hyp
orefl
exia
(
the
rape
uticran
ge)
N
RTIs
AZT
ABC
243
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-
2)
Met
abol
ic a
bnor
mal
ity
Fatmaldistrib
ution
N
RTIs
d4T
P
Is
boo
sted
PIs
lipoh
ypertro
phy
P
Is
lipoh
ypertro
phy
(
)
lipoa
troph
y
N
RTIs
d4T
dd
I
AZT
d4T,A
ZTA
BC,
TDF
244
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-
Hyp
erglyc
emia
insu
linresistan
ce
P
Is
FB
S>
126mg/dL
rand
omblood
su
gar
20
0mg/
dL
FBS
OGTT
P
Is
FB
S
rand
omblood
suga
r
FBS
6
Hyp
erlip
idem
ia
P
Is
N
NRTIs
EFV
hype
rlipide
mia
NVP
Cho
lesterol,LD
L
athe
rosc
lerosis
TG
panc
reatitis
Fa
sting
choles
terol
>200
mg/dL
Fa
stingLD
L
>130
mg/dL
Fa
stingTG
>200
mg/dL
Fa
sting
choles
terol,
HDL,LDL
TG
6
6-12
pan
crea
titis
TG
>500
mg/dL
P
Is
NNRTIs
NNRTIs
ATV
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cho
lest
erol
statin
-Prava
statin(
2,000 copies/mL**
genotyping
adherence
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4.7.1 genotyping
1) genotyping
viralload2,000copies/mL
1
2) NRTIs3TC
(mutation) Thymidine Analog
Mutations(TAMs)TAMs4NRTIs
NRTIsTAMs
4NRTIsTDF,ddIABC
multi-NRTImutation(Q151M,69i)NRTIs
(Q151MTDF)K65RTDF
NRTIs
boostedPIsNRTIs
3) 3TC
NRTIsM184V
M184I3TC3TC
M184V(lessviralfitness)
263
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4) genotyping
noevidenceofresistance,possibleresistanceresistance
mutationsgenotyping
4[6a]
possibleresistanceresistance
NRTIs
(recycle)
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4[6
a]
ge
notyping
NRTIs
(
)
NRTI
s
M
utat
ions
NRTI
s
AZT
d4T
-TA
Ms:M
41L,D
67N,K70
R,
L210
W,T2
15YF
,K21
9QE
-Multi-NRTI:Q15
1M
complex
(A62
V,V75
I,F7
7L,
F116
Y,Q
151M
),69
inse
rtion
-
TAMs
-
NNRTIs
Mutations
NVP,EFV Y181C/I,K103N,G190S/A,
L100I,V106M/A,V108I,
Y188CLH,P225H
mutation
NVPEFV
4.7.2 genotyping PIs
PIsNRTIs
NNRTIsPIsRTV
(boosting)PIsPIs
PIs2
1) mutationmajormutation
minormutationPIs
majormutationcrossresistance
LPV/rRTV
4[6b] genotypingNNRTIs
NNRTIs ETR
mutation score Update of the Drug Resistance
MutationsinHIV-1NVPEFVmutation
scoreETR
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2) mutation
mutation5
mutation
(geneticbarrier)
DRV/r
4.7.3 2NRTIs + 1NNRTI
2NRTIs+
1NNRTI(NVPEFV)
1) :2NRTIs(
genotyping)+LPV/r
2) :
2.1) 2NRTIs ( genotyping) +
ATV/rATV
6
2.2) Double-boostedPIsLPV/r+
SQVLPV/r+IDV
NRTIsNRTIs
NNRTIs
TDF
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adherence
double-boostedPIs
double-boostedPIs viral suppression
1
boosted PI +
2NRTIs/3NRTIs
1 NRTIs
2NRTIsresistancetesting
4[4](
2NRTIsAZT+d4T,d4T+ddI,TDF+ddI)
1: mutation TAMs
4NRTIs
(recyclingNRTIs)ddI+AZT,ddI+3TC,ABC+3TC,ABC+ddI
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2: TDF
mutation TAMs 4
Q151M69iK65R
1230kgTDF
TDF+3TC,TDF+ABCTDF+AZT
AZTNRTI3TDF+3TC+AZTTDF+ABC+
AZTAZTK65R
TDF
3: TDF
mutation TAMs 4
Q151M69iK65R
NRTIsNRTIs
ddI+ABC,ddI+3TCddI+AZT
NRTIsdouble-boostedPIs
3TC
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4[7a] NRTIs
NRTI
TDF
- TAMs
-
-
-
30 kg
Tannerstage>4
ABC -
lipodystrophy
-
-
-hypersensitivity
6ABC
HLA-B*5701 genotype
HLA-B*5701
ABC
-
TDF2553
www.ClinicalTrial.govNCT00352053www.ClinicalTrial.govNCT00528957
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2 PI
LPV/r
PIIDV/r
LPV/r
3 double-
boostedPIsLPV/rIDVSQV
4[7b]PIs
PI
LPV/r
-
-
-PIRTV
-
-
-43%
-
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PI
ATV/r -RTV
ATV
-
->6
-
LPV/rIDV/r
-
-RTV
-
-
conductionsystemdefect
prolongedPRinterval
-indirecthyperbiliru-
binemia
SQV/r
-RTV
SQV
-
-
LPV/rIDV
-LPV/r
doubleboostedPIs
-
-RTV
-
-
-double
boostedPIs
PIs
-50mg/kg12.
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-
PI
IDV/r -RTV
IDV
-
-LPV/r
doubleboostedPIs
-
-RTV
-
-double
boostedPIs
PIs
-220-300mg/m2
12.
-
2
trough0.1g/L
2.
10g/L
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4[4]
viral load 3-6
- single boosted PI NRTIs
ddI + ABC, ddI + 3TC ddI + AZT
LPV/r ATV/r
- double-boosted PIs
LPV/r + SQV LPV/r + IDV
3TC, AZT + 3TC, ABC + 3TC
1 boosted PI
: LPV/r
: ATV/r
TDF + 3TC TDF + ABC TDF + AZT
AZT NRTI 3
TDF + 3TC + AZT TDF + ABC + AZT
ddI + 3TC, ddI + AZT,
ABC + 3TC, ABC + ddI
>12
>30 kg
TDF + 3TC,TDF + AZT,
TDF + ABC
3
TAMs >4 69i
K65R
30 kg
2 NRTIs
2 2NRTIs genotype + 1 boosted PI
genotyping
viral load >2,000 copies/mL*
6
d4T AZT + 3TC + NVP EFV
*viralloadgenotyping
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4.7.4 3 NRTIs, NNRTIs PIs
3
2
genotypicresistance
testing
FTC(NNRTI),
DRV/r(PI),RAL(INSTI),maraviroc(CCR5inhibitor)
DRV/r 6
viralload6viralload
1,000copies/mL
CD4
NNRTIs
NNRTI CD4
3TC
mutation CD4
(3)
4.7.5 NRTIs 2 (dual NRTIs therapy)
1-2
NRTIs
275
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viralload50copies/mL2NRTIs+
1NNRTI viral load genotypic resistance
testing4.7.6
4.7.6 dual NRTIs
1) 2NRTIsgenotyping+boostedPI
NRTIsPIs
2NRTIs+1NNRTI
2) 2
2.1) 2NRTIs + 1NNRTITAMs
4 multi-NRTI mutation
NNRTIsNRTIs
2.2) NNRTI + booosted PI + 1NRTI/2NRTIs(recycle)
NRTIs
TAMs4multi-NRTImutation
NNRTIsPIs
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4.7.7
1) 1
3
adherencePIsmetabolic
lipidprofile2TDF
IDVurinalysis,Cr*bloodsugar6
CrCl50mL/minTDF
2) 1
32-3CD4
3-66viralload
6
viral load1,000copies/mL6
3)
PIs 2
PIs
double-boostedPIs
IDV/rSQV/r25kg
PIs2
*creatinineclearance
277
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4.8
T cell B cell
CD4
%CD415
%CD425CD4350cells/mm3
(>5)6%CD415viral
suppression400copies/mL1
4[8]
CD4
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%CD415
4[8]
%CD415
*
**MMR
1 2 6
HBVvaccine HBV1 HBV2 HBV3 3
JEvaccine* JE1 JE2 2
Measlesvaccine** MMR1 1
dTvaccine
>710
279
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4.9
4.9.1
41)2)
3)
4)
4.9.2
10
280
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4.10 (adherence to antiretroviral treatment in children)
adherence
95
adherence
5
1 :
281
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2 :
1-2
DOT
TMP-SMX
2-4
3 :
(fixeddosecombination)
TDF+3TC+EFV
4 :
5
:adherence
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4.11
(5Ds)
D1-Disclosure :
9-10
1)
2)3)
4)
5)
D2-Depression : 13
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D3-Drug :
D4-Dangers :
9-12
12-14
D5-Daily activity :
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1. CentersforDiseaseControlandPrevention.Guidelinesfortheprevention
andtreatmentofopportunistic infectionsamongHIV-exposedandHIV-
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