Professional Documents
Culture Documents
(TH) Hiv 2017 PDF
(TH) Hiv 2017 PDF
2560
Thailand National Guidelines on HIV/AIDS Treatment and Prevention 2017
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HIV-NAT
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HIV-NAT
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1
2560 2,000
4
5
2
2535
2545
3
2557
CD4
.. 2559
/
2557
2560
2560
6
7
(Introduction) 29
2 33
(HIV Laboratory for Diagnostic and Monitoring)
2.1 35
(HIV Testing and Counselling; HTC)
2.2 39
2.2.1 (HIV viral testing) 39
2.2.2 40
2.3 55
2.3.1 CD4 (CD4 count) 55
2.3.2 (HIV viral load) 56
2.3.3 58
(HIV drug resistance testing)
2.4 61
2.5 (false positive) anti-HIV 64
2.6 65
2.6.1 65
2.6.2 66
3.4.2 78
(Multi-class antiretroviral treatment failure)
3.5 80
3.6 81
3.7 (Drug-drug interaction) 83
3.8 110
3.9 115
3.10 116
3.11 121
3.12 134
()
3.13 137
(Adherence to antiretroviral therapy)
3.14 Immune reconstitution inflammatory syndrome (IRIS) 137
3.15 141
3.15.1 141
(Acute HIV infection)
6 (Recent HIV infection)
3.15.2 144
3.15.3 155
3.15.4 158
3.15.5 161
3.15.6 164
3.15.7 165
3.15.8 166
3.16 173
8
9
4 177
(Management of HIV-Infected Children and Adolescent)
4.1 181
4.1.1 181
4.1.2 182
4.2 (Early infant diagnosis) 191
4.3 197
(ARV therapy in nave HIV-infected children)
4.3.1 198
4.3.2 201
4.3.3 203
(antitretroviral nave)
4.3.4 205
3
4.3.5 206
(antiretroviral therapy in children with opportunistic infection)
4.4 210
4.4.1 210
4.4.2 211
4.4.3 212
4.5 213
4.6 214
(Immune Reconstitution Inflammatory Syndrome: IRIS)
4.7 218
4.7.1 > 3 LPV/r 218
4.7.2 218
4.7.3 218
4.8 219
(diagnosis of treatment failure in HIV-infected children)
4.9 221
4.10 HIV genotyping 223
4.10.1 225
2NRTIs + 1NNRTIs
4.10.2 226
2NRTIs + PI
4.10.3 3 NRTIs, NNRTIs 227
PIs (salvage regimen)
4.10.4 229
4.11 230
4.12 232
4.13 234
4.14 235
(adherence to antiretroviral treatment in children)
4.15 238
4.16 (Transition to adult clinic) 239
10
11
5 243
(Prevention of Mother-to-Child HIV Transmission)
5.1 248
5.1.1 249
5.1.2 252
5.2 255
5.3 260
5.3.1 262
5.3.2 264
5.3.3 271
5.3.4 271
5.3.5 274
5.4 282
5.5 285
5.5.1 285
5.5.2 285
5.6 287
5.7 287
5.7.1 287
5.7.2 289
5.8 290
(Early infant diagnosis EID)
6 293
(Opportunistic Infections: Prophylaxis and Treatment)
6.1 (Tuberculosis) 293
6.2 313
6.2.1 Pneumocystis pneumonia (PCP) 314
6.2.2 Cryptococcosis 318
6.2.3 Candidiasis 321
6.2.4 Toxoplasmic encephalitis 324
6.2.5 Penicilliosis histoplasmosis 327
6.2.6 Cytomegalovirus (CMV) infection 331
6.2.7 Mycobacterium avium complex (MAC) infection 334
8 379
(Service delivery guidance)
8.1 (Reach & Recruit) 381
8.2 (Test) 392
8.3 (Treat) 400
12
13
437
439
(Dose and Route of HIV medication in Adults)
CDC Classification 2014 449
451
(WHO Classification System for HIV-Infected Children)
454
(Dose and Route of HIV Medication in Pediatrics)
464
creatinine clearance 475
476
480
481
482
rapid desensitization TMP-SMX 484
485
509
2560
Thailand National Guidelines on HIV/AIDS Treatment and Prevention 2017
2.1 40
2.2 41
99.5 99.0
2.3 61
2.4 63
2.5 64
3.1 69
3.2 70
3.3 72
3.4 75
3.5 75
3.6 virological failure 77
3.7 79
3.8 79
3.9 80
3.10 83
3.11 85
6
3.12 88
14
15
3.33 164
3.34 PIs methadone 165
3.35 TDF 167
3.36 174
4.1 183
.. 2559
4.2 1-6 190
4.3 7-18 190
4.4 195
4.5 202
.. 2559
4.6 203
4.7 1 204
4.8 213
4.9 227
4.10 231
CD4 < 15
16
17
5.1 249
5.2 254
5.3 262
5.4 HAART 263
5.5 265
5.6 280
5.7 282
5.8 283
HAART
5.9 100 g OGTT 284
5.10 290
6.1 297
6.2 298
6.3 299
6.4 303
6.5 304
6
6.6 304
rifampicin
18
19
8.1 415
8.2 418
8.3 431
1 437
2 439
3 449
CD4
4 450
5 454
6 rapid desensitization TMP-SMX 484
2.1 36
2.2 43
24
2.3 52
24
2.4 60
3.1 135
3.2 anti-HCV 148
3.3 TDF 169
HIV
5.1 258
5.2 259
5.3 279
6.1 310
(treatment latent tuberculous infection isoniazid preventive therapy)
6.2 312
20
21
7.1 357
7.2 (GC) (CT) 370
.. 2553-2557
7.3 373
8.1 380
8.2 387
8.3 390
8.4 407
8.5 3x4 426
8.6 429
8.7 433
/r Ritonavir boosted
3TC Lamivudine
ABC Abacavir
ATV Atazanavir
AZT Zidovudine
CCBs Calcium channel blockers
COBI Cobicistat
d4T Stavudine
DCCBs Dihydropyridine calcium channel blockers
ddl Didanosine
DMPA Depot medroxyprogesterone acetate
DRV Darunavir
DTG Dolutegravir
E Ethambutol
EE Ethinyl estradiol
ENG Etonogestrel
EFV Efavirenz
ETR Etravirine
EVG Elvitegravir
FTC Emtricitabine
HRAs H2-receptor antagonists
IDV Indinavir
LNG Levonorgestrel
INH, H, I Isoniazid
LPV/r Lopinavir/ritonavir
MVC Maraviroc
NET Norethindrone
NFV Nelfinavir
NGM Norgestimate
NRTI Nucleoside reverse transcriptase inhibitor
NSAIDs Nonsteroidal anti-inflammatory drugs
NVP Nevirapine
PAS Para-aminosalicylic acid
PI Protease inhibitor
PPIs Proton pump inhibitors
PZA, Z Pyrazinamide
R Rifampicin
RAL Raltegravir
RPV Rilpivirine
RTV Ritonavir
SQV Saquinavir
TCAs Tricyclic antidepressants
TDF Tenofovir
TMP Trimethoprim
TMP-SMX Trimethoprim/sulfamethoxazole
24
25
AFB Acid-fast bacilli
AHI Acute HIV infection
ALT Alanine aminotransferase
ARS Acute retroviral syndrome
AST Aspartate aminotransferase
AUC Area under the curve
BMD Bone mineral density
BMI Body mass index
CBC Complete blood count
CD4 Cluster of Differentiation
CITC Client-initiated testing and counseling
CMV Cytomegalovirus
CrCl Creatinine clearance
CT Chlamydia trachomatis
CXR Chest x-ray
DAA Direct Acting antivirals
DOT Directly observed therapy
DSC Disease specific certification
DXA Dual energy x-ray absorptionmetry
EBV Ebstein-Barr virus
EID Early infant diagnosis
EM Erythema multiforme
EWI Early warning indicators
FBS Fasting blood sugar
FDA Food and Drug Administration
GCT Glucose challenge test
26
27
PCR Polymerase chain reaction
PDCA Plan do check act
PEP Post-Exposure Prophylaxis
PITC Provider-initiated testing and counseling
PML Progressive multifocol leukoencephalopathy
PMTCT Prevention of mother-to-child transmission
PrEP Pre-Exposure Prophylaxis
PwP Prevention with positives
RPR Rapid plasma reagin
SDR Same day result
SJS Stevens Jonhson syndrome
TAMs Thymidine analog mutations
TasP Treatment as Prevention
TB Tuberculosis
TEN Major/Toxic epidermal necrolysis
TG Triglyceride
TLTI Treatment latent tuberculous infection
TST Tuberculin skin test
UIC Unified identification code
UNAIDS
UP Universal precaution
VCT Voluntary counseling and testing
VDRL Venereal disease research laboratory test
VL Viral load
WHO World Health Organization
.
28
Introduction
29
36.7
17 15
1.8 1.5
Sub-Saharan Africa .. 2558
2.1 1.1
15 1.5 1.1
35
.. 2543 (Millennium Development
Goal; MDG) 43 .. 2546
32 .. 2547
(Latent TB)
(Sustainable Development Goals; SDG)
SDG 3
3.3
.. 2573
(AIDS epidemic model Spectrum) .. 2559 423,778
1.1 15-49
179,590 6,304
1,821 15 78
3,180
15 3,221
.. 2558
284,434 65
.. 2543 2553
65 .. 2553
30
.. 2557
(Treatment
as prevention)
(Same
Day Result HIV Testing)
CD4 2558 32,926
2557 27,884 CD4
2556, 2557 2558 125,
129 196 cells/mm3
.. 2556 2.3
2.1 .. 2557 1.9 .. 2558
2559
(Elimination of Mother to Child Transmission on HIV and Syphilis)
30
Introduction
31
(Pre-Exposure Prophylaxis)
Tenofovir Emtricitabine
28 .. 2557 .. 2573
1,000
2559
.. 2573 .. 2563
500,000 500,000
90
90
90 1,000 copies/mm3
90-90-90
.. 2563 30
75
/
.. 2560
32
HIV Laboratory for Diagnosis and Monitoring
33
2
(HIV Laboratory for Diagnostic and Monitoring)
(Verbal consent)
3 rapid test 3
(inconclusive) 2 / 1
1
24
HIV DNA PCR 7
CD4 CD4
VL 1
VL > 1,000 copies/mL
.. 2573
.. 2563 3 90
90
90
RRTTR (Reach-Recruit-Test-Treat-Retain)
.. 2558-2562
90
34
HIV Laboratory for Diagnosis and Monitoring
35
2.1
(HIV Testing and Counselling; HTC)
(Verbal
consent)
(pre-test/post-test
counselling) 2.1
(group counselling)
(individual counselling)
2
(client-initiated testing
and counselling; CITC) (provider-initiated testing
and counselling; PITC) PITC
(WHO) (UNAIDS)
2.1
CITC PITC
(Pre-test counseling)
PrEP
(ongoing counseling)
36
HIV Laboratory for Diagnosis and Monitoring
37
rapid test
(machine based)
3
1-2
1)
2)
- - -
3)
4)
5)
6)
7)
8)
9)
10)
38
HIV Laboratory for Diagnosis and Monitoring
39
2.2
p24 Antigen
p24
Qualitative
NAT
1
(Positive or Negative)
Thailand National Guidelines on HIV/AIDS Treatment and Prevention 2017
2560
2.2.2
Enzyme-linked immunosorbent assay : ELISA,
agglutination assay, immonochromatography dot immunoassay
.. 2551
.. 2552
(sensitivity) (specificity)
2.1
2.1
1 p24 antigen 100 99.5
2 100 99.5
3 anti-HIV 99.5 99.0
: 14
.. 2552
40
HIV Laboratory for Diagnosis and Monitoring
41
2.2.2.1
(predictive value) (positive predictive value: PPV)
(negative predictive value: NPV) PPV NPV
2.2
.. 2558 0.82
PPV NPV 99.99
3 UNAIDS WHO
3 2.2
2.2
99.5
99.0
Prevalence %PPV: 1 test %PPV: 2 tests %PPV: 3 tests %NPV
0.05 14.292 83.200 99.99460 100.00
0.5 62.594 99.821 99.99946 99.999
0.82 73.356 99.891 99.99967 99.999
2.0 87.173 99.956 99.99987 99.998
5.0 94.602 99.983 99.99995 99.995
10.0 97.368 99.992 99.9998 99.989
2.2.2.2
3
3
3 2 3
(machine based assay) rapid test
simple test 1 2
3
rapid test
rapid test
2.2.2.3
24
24
3 UNAIDS WHO 2.2
42
HIV Laboratory for Diagnosis and Monitoring
43
2.2
24
1 (A1)(1)
A1_ A1+
2 (A2)(1)
A1 A2
3
(A3)(1)
(anti-HIV negative) (inconclusive)(3,4) (anti-HIV positive)(2)
(1) A1, A2 A3 1, 2 3
1
2 3
(2) (positive)
(newly diagnosed)
2 1
(3) (inconclusive) 2
1 A1, A2 A3
1
(4)
2 / 3
(3)
qualitative NAT
neutralization p24 assay window period
(Anti-HIV)
1) (anti-HIV negative)
(non-reactive)
2) (anti-HIV positive) 3
(reactive)
3) (inconclusive) 3
2 / 1
44
HIV Laboratory for Diagnosis and Monitoring
45
2
(human error)
1
2
CD4 /
(retesting)
3
1.
1.1
/
1.2 (discordant couple)
1.3 window period
1.4
1
1.5
1.6
1.7
1.8 (PEP)
(PrEP)
1.9
1
2.
2 / 1
2.1 (seroconversion)
2.2 (fasle positive)
3.
3.1
OPD card
3.2
3.3
CD4 CD4 > 500 cell/mm3
5
46
HIV Laboratory for Diagnosis and Monitoring
47
2.2.2.4
24
24
12 95
18
18-24
12 < 24
24 12
30 1
50 2
PCP
DNA PCR
2 2.3
DNA PCR
DNA PCR
24
2
(1) (dried blood spot; DBS)
EDTA
.
(DBS)
(2)
EDTA ACD 0.5-2.0 mL
48
HIV Laboratory for Diagnosis and Monitoring
49
-
.
-
12
DNA PCR
( 2.3)
1. PCR 7
2.3
2. PCR 1
PCR
3.
PCR ( 4-6
4 5)
4. PCR 1 PCR
(standard risk)
PCR 2 2-4 (high risk)
PCR 2 2 4
. 2
2.3
. 2
2 4 PCR
4
2.3
24
12-24
1. 12-24
.
.
18
5-10
18
24
PCR
2.
(HIV Ag/Ab)
18
PCR
HIV Ag/Ab
18
24
50
HIV Laboratory for Diagnosis and Monitoring
51
1. (Definitive exclusion of HIV infection)
24
. PCR 2
2 2
4
. 6
2 PCR
. PCR 1 4
1 6
CD4
2. (Presumptive exclusion of HIV infection)
. PCR 2
2
. PCR 1
2
4
PCR
. 6 1
PCR
CD4
(Positive) (Negative) (Positive) (Negative) (Positive)(9) (Negative)
DNA PCR DNA PCR DNA PCR Anti-HIV
2 18
(Positive) (Negative) (positive) (negative) (Negative) (Positive) (Positive)(10) (Negative)(11)
2560
Anti-HIV
(4) (5)
24
DNA PCR DNA PCR
4 (Positive) (Negative)
(12)
(Positive) (Negative) (Negative) (Positive) (Anti-HIV Positive) (Anti-HIV Negative)
(8) 24
(9) 12-24 Anti-HIV HIV DNA PCR PCR
(10) 3 3
2
(11) PCR 2
(12) 6
5
proviral DNA DNA PCR HIV RNA
HIV RNA HIV RNA (qualitative
HIV RNA)
(copies/mL)
(quantitative HIV RNA)
HIV RNA (qualitative HIV RNA)
(in-house)
54
HIV Laboratory for Diagnosis and Monitoring
55
2.3
CD4
CD4 2
Flow cytometry Flow cytometry
CD4 point-of-care
point-of-care
Flow cytometry
IQC EQA
CD4
CD4
CD4 350
cells/mm3 CD4 2
CD4 > 350 cells/mm3 CD4
VL 50 copies/mL
VL < 50 copies/mL 1 CD4
VL < 50 copies/mL
2 CD4
CD4
CD4
steroid
CD4
56
HIV Laboratory for Diagnosis and Monitoring
57
Viral load
VL
2
1
6 12
1
VL copies/mL ( IU/mL) Log10
equivalence
EDTA ACD
6
/
VL
1
VL > 1,000 copies/mL ( 2.4)
VL
Viral load
10
VL
4
VL
VL > 1,000 copies/mL (
2.4)
VL
EDTA ACD
58
HIV Laboratory for Diagnosis and Monitoring
59
6
/
2.5
2.4
Viral load 6 1
viral load < 1,000 copies/mL viral load > 1,000 copies/mL
drug resistance(2)
(1)
VL EDTA 6 - 9 mL
VL -20 -70C
(2)
VL drug
resistance
60
HIV Laboratory for Diagnosis and Monitoring
61
2.4
CD4 VL
ISO15189
CD4 VL
2.3
CD4 dual platform
(CBC analysis machine)
2.3
(IQC) (EQA)
IQC
HIV testing (machine based)
3 2 levels
IQC
HIV testing (simple test)
3 1 levels
IQC
HIV testing (rapid test)
3 1 level
1
IQC
CD4 count
6 1 level
IQC
Viral load testing
2 1 level
IQC
Drug resistance testing
2 1 level
CD4, VL
US FDA
CE mark IVD
CD4 VL
(WHO prequalification of diagnostics program)
2
3
/
62
2.4
Anti-HIV testing EIA/CMIA/ECIA, Clotted blood 5 mL 2-8C
agglutination test, Serum or EDTA 1 mL 24 .
immunochromatography plasma
HIV testing(1) Nucleic acid amplification EDTA blood 2-3 mL 2-8C
testing (NAT) EDTA plasma 1 mL 24 .
Dried blood spot 1
CD4 count Flow cytometry POCT EDTA blood 2-3 mL (18-25C)
6 . ( 18-25C
)
Viral load testing Real time nucleic acid EDTA or ACD blood 6-9 mL 6 .
(HIV-1 RNA) amplification EDTA ACD 2 4-8C 24 .
Plasma 1.5 mL 6 .
HIV Laboratory for Diagnosis and Monitoring
2560
2.5
Stanford
ViroSeq
(in-house)
(mutation) Susceptible / Potential
None
low level resistance
mutation Possible Low level resistance
resistance Intermediate resistance
mutation
Resistance High level resistance
( )
(false positive)
anti HIV
(antibody cross reactivity)
(mycobacteria)
(giardia) (cytomegalovirus; CMV)
64
HIV Laboratory for Diagnosis and Monitoring
65
(influenza vaccination)
(human leukocyte
antigen; HLA) 1
2.6
2.6.1
(first generation sequencer)
(Sanger sequencing)
800 (mutant virus)
(wild type virus)
(second generation sequencer) next generation
sequencer massively parallel sequencing
PCR 200-400
(Chip)
flow cell
(single mutation)
(sensitivity)
Thailand National Guidelines on HIV/AIDS Treatment and Prevention 2017
2560
2.6.2
(severe adverse drug reaction)
(Stevens Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN))
.
HLA-B*57:01 (drug
hypersensitivity) Abacavir
HLA-B*35:05
(single nucleotide polymorphism)
Nevirapine
HLA-B*40:01
(lipodystrophy) Stavudine
CYP2B6 Efavirenz
(Efavirenz-associated CNS symptoms)
(good compliance)
VL
66
Management of HIV-Infected Adult
67
3
(Management of HIV-Infected Adult)
CD4
CD4 > 500 cells/mm3 serious AIDS-related
serious non-AIDS CD4 350
cells/mm3 Kaposi sarcoma
malignant lymphoma
VL < 50 copies/mL 2
CD4
EFV
EFV 600 ./ 400 ./ ( EFV 400 .
rifampicin) NNRTIs
RPV NVP
RPV VL VL > 500,000
copies/mL
VL RPV CD4 > 350
cells/mm3 VL < 50 copies/mL 6
2
(< 50 copies/mL) CD4
(AIDS-related illness)
(Non AIDS-related illness)
(adherence)
95 2
12 1 24
68
Management of HIV-Infected Adult
69
3.1
3.1-3.3
3.1
()
CD4
(current lifestyle) 6 12
EFV
1
Management of HIV-Infected Adult
1 1
drug adherence
HBsAg anti-HBs
Anti-HCV anti HCV: negative
active IDU ( ) CD4
< 100 cells/mm3 CD4
Syphilis (VDRL) MSM 6
3
ALT 3
Creatinine TDF ATV 6
50 < 45 .
1
Total cholesterol 1 1 < 35
Triglyceride 1 /
Fasting blood sugar < 35
2 /
35 2 /
Urinalysis TDF ATV Fanconi syndrome
50 TDF (tubular dysfunction)
< 45 . PIs TDF
NSAIDs 6 3.15.8
Management of HIV-Infected Adult
1
Chest X-ray
Drug resistance VL > 1,000 copies/mL
6
PrEP
Pap smear 1 1
Anal PAP 1 1
Serum cryptococcal Ag CD4 < 100 cells/mm3
3.2
CD4
Adherence
3.3
3.4
NRTIs + NNRTIs TDF/FTC TDF + 3TC
EFV
74
Management of HIV-Infected Adult
75
3.4
NRTIs backbone NNRTIs
TDF/FTC
EFV RPV2 LPV/r
TDF + 3TC1
+
ABC + 3TC + NVP ATV/r
AZT + 3TC NNRTIs
INSTI4
RAL
EVG/c/TDF/FTC3
DTG
1
2
RPV-Rilpivirine 25 . 3.5
3
Elvitegravir/cobicistat/TDF/FTC 1
4
3.5
NRTIs ABC + 3TC AZT +
3TC
ABC
TDF VL < 100,000 copies/mL ( dolutegravir)
EFV 600 ./ 400 ./
EFV ( EFV 400 .
rifampicin)
NNRTIs RPV
RPV
VL VL > 500,000 copies/mL
VL
CD4 > 350 cells/mm3
RPV
RPV VL < 50 copies/mL
6 NNRTIs
Thailand National Guidelines on HIV/AIDS Treatment and Prevention 2017
2560
EFV adherence EFV
EFV
2
RPV VL > 500,000 copies/mL
PIs LPV/r ATV/r
NNRTIs 3
d4T VL d4T TDF ABC
< 50 copies/mL
integrase inhibitors
3.4 3 RAL DTG
DRV/r
2
NNRTIs
(EFV/NVP intolerance) rifampicin
VL VL < 50
copies/mL RPV PI
ABC HLA-B*5701
ABC
ABC
(hypersensitivity reaction) HLA-B*5701
HLA-B*5701
ABC 6
2 (1) (2) (3)
(4) (5)
creatine phosphokinase lymphopenia
ABC Child-Pugh Score of 7-12
76
Management of HIV-Infected Adult
77
3.4
3.4.1
3 (1) virological failure
(2) immunological failure (3) clinical failure
1 2
3
virological failure
: virological failure HIV RNA (VL) > 200
copies/mL 6
(1) NNRTIs VL
> 1,000 copies/mL
(2) boosted-PIs
poor adherence
VL 50 copies/mL
LPV/r + AZT
1
VL
VL > 1,000 copies/mL
2-6
4
3.7 3.8
3.4.2
(Multi-class antiretroviral treatment failure)
VL < 50 copies/mL
3
3 2
VL 3
78
Management of HIV-Infected Adult
79
3.7
1.
2. 3
integrase inhibitor
3.
1) Integrase inhibitors: RAL, DTG
2) Protease inhibitors: DRV ()
3) NNRTIs: ETR ()
3.8
Mutation
NNRTIs + NNRTIs-associated mutation AZT TDF
NRTIs (EFV, NVP) M184I/V + 3TC (FTC) + boosted PIs boosted PIs
NRTIs mutation + INSTI (RAL DTG)
RPV TDF AZT
E138K M184I/V NRTIs + 3TC (FTC) + boosted PIs boosted PIs
mutation + INSTI (RAL DTG)
Boosted- M184I/V PIs adherence / drug interaction
PIs + NRTIs resistance mutation adherence
adherence
M184I/V + NRTIs mutation AZT TDF
PI resistance + 3TC (FTC) + boosted PI
mutation TDF AZT
+ 3TC (FTC) + boosted PI
Mutation
Boosted- M184I/V + PIs resistance genotypic
PIs + NRTIs mutation resistance
()
INSTI- M184I/V INSTI resistance Boosted PIs + NRTIs (
based + mutation )
NRTIs Boosted PIs + DTG genotypic
resistance
PI-based regimen
rifampicin ( 6 )
rifampicin lopinavir double-dose LPV/r (800/200)
12 .
TDF + 3TC (FTC)
3.5
3.9
1 NRTIs + 1 NNRTIs
1 NRTIs + 1 PIs boosted
RTV
1 NRTIs + RAL 2 NRTIs
Triple NRTIs combinations
TDF + 3TC + ABC
2 NNRTIs combination
80
Management of HIV-Infected Adult
81
d4T + AZT Pharmacologic antagonism
FTC + 3TC resistance profile
TDF + ddI ddI
d4T + ddI peripheral neuropathy, pancreatitis,
hyperlactatemia lactic acidosis
2
ATV + IDV hyperbilirubinemia
NRTIs
2
NVP
CD4 > 400 cells/mm3
CD4 > 250
cells/mm3
d4T
VL < 50 copies/mL
3.6
12
TDF/FTC 3TC EFV RPV
3.10 AZT d4T TDF VL < 50 copies/mL
HBV (HBsAg)
EFV
1-2 RPV
proton pump inhibitor
()
12
82
Management of HIV-Infected Adult
83
3.10
EFV EFV
NVP NVP 400 . 24 . RPV 25 .
RPV 25 .
1
LPV/r LPV/r 2 12 . 4 24 .
ATV/r 1
TDF TDF
AZT d4T TDF 24 .
VL < 50 copies/mL TDF
3TC 3TC (150 .) 1 12 . 300 . 24 .
TDF/FTC 1 1
NNRTIs PIs
cytochrome P450 (CYP450) CYP3A4 isoenzyme
PIs
CYP450 p-glycoprotein NRTIs
CYP450 ddI
hydroxyurea, ribavirin TDF
3
1) CYP inducer CYP inducer CYP450
CYP450
rifampicin CYP inducer NNRTIs
PIs rifampicin
EFV
PIs
2) CYP inhibitor CYP inhibitor CYP450
CYP450
RTV CYP inhibitor PIs
PIs
boosted PIs
3) CYP inducer CYP inhibitor EFV NVP
(substrate) CYP450 CYP inducer
84
3.11 6
//
1) Ergotism Ergot CYP450 CYP inhibitor Ergot
clarithromycin, ketoconazole, NNRTIs EFV PIs RTV
(peripheral vascular vasoconstriction)
(ischemia)
/
() (cyanosis) (gangrene)
(vasodilator drug) prostaglandin analogue
PIs, EFV EVG/c Ergot derivative ergotamine
Management of HIV-Infected Adult
NVP
90
Itraconazole () EVG/c itraconazole itraconazole
EVG/c itraconazole (> 200 ./)
itraconazole
Ketoconazole EFV Ketoconazole
ETR Ketoconazole ketoconazole
ETR
NVP Ketoconazole AUC 72%
NVP 15-30%
EVG/c Elvitegravir AUC: 48%; ketoconazole > 200
Cmin: 67% ./
2560
ETR ETR
EVG/c Posaconazole posaconazole
EVG/c
Voriconazole EFV Voriconazole: AUC 77% voriconazole 400 .
EFV: AUC 44% 12 . EFV 300 . 24 .
ETR Voriconazole 14% voriconazole
ETR AUC 36% voriconazole
Voriconazole () NVP Voriconazole voriconazole
NVP
RPV Voriconazole
RPV voriconazole
EVG/c Voriconazole / voriconazole
EVG/c voriconazole
(anticonvulsants)
Carbamazepine, EFV Carbamazepine + EFV: EFV
phenobarbital, Carbamazepine AUC 27%
phenytoin EFV AUC 36%
Phenytoin + EFV: EFV
Management of HIV-Infected Adult
phenytoin
ETR Anticonvulsant ETR
RPV RPV
NVP Anticonvulsant NVP NVP
EVG/c carbamazepine AUC 43%
EVG AUC 69% and Cmin > 99%
COBI expected
azithromycin ( MAC)
Rifabutin 300 .
:
rifabutin AUC
25-O-desacetyl-rifabutin AUC 625%
EVG AUC 21%, Cmin 67%
Rifampicin EFV EFV AUC 26% EFV 600 ./ EFV
ETR ETR
RPV RPV 80%
bosentan 62.5 .
PI ( unboosted ATV) bosentan
bosentan 36 . PI
PI 10 62.5 .
EVG/c Bosentan EVG/c 10 :
bosentan 62.5 .
Bosentan () EVG/c Bosentan bosentan EVG/c:
bosentan 36 . EVG/c
EVG/c 10
bosentan 62.5 .
Sildenafil PIs Sildenafil sidelnafil 25 . 25 .
+ DRV/r sildenafil boosted PIs
sidelnafil 100 . DRV/r
RPV Sildenafil
ETR Sildenafil 57% ETR
EVG/c Sildenafil pulmonary hypertension EVG/c
Management of HIV-Infected Adult
myopathy rhabdomyolysis
Pravastatin, EFV Pravastatin AUC 44% pravastatin rosuvastatin
Rosuvastatin Rosuvastatin
ETR
EVG/c Pravastatin
Rosuvastatin AUC 38% and Cmax rosuvastatin
89%
Pitavastatin EFV Pitavastatin AUC 11%, Cmax 20%
ETR, NVP, RPV
All PIs ATV Pitavastatin AUC 31%,
Cmax 60%
LPV/r Pitavastatin AUC 20%
DRV/r Pitavastatin
Oral anticoagulant
Warfarin EFV, NVP Warfarin INR warfarin
ETR Warfarin INR warfarin
All PIs Warfarin INR warfarin
EVG/c Warfarin INR warfarin
Management of HIV-Infected Adult
Clopidogrel ETR clopidogrel
Salmeterol, long-acting EVG/c Salmeterol salmeterol
2 adrenergic receptor
colchicine 0.3 .
Metformin DTG DTG 50 . metformin 1,000 ./
metformin 500 . 2 : / DTG metformin,
Metformin AUC 79%, Cmax 66% metformin
DTG 50 . 2 metformin GI
500 . 2 :
Metformin AUC 2.4 , Cmax 2
Opioid antagonist
Methadone Boosted PIs R-methadone (active form methadone withdrawal
methadone) methadone
LPV/r methadone 26-53%
ATV/r, DRV/r methadone
( methadone 16-18%)
EFV, NVP methadone 41-52% methadone withdrawal
methadone
ETR methadone
RPV R-methadone AUC 16% methadone
Management of HIV-Infected Adult
unboosted ATV
EFV,ETR,NVP Cmin Daclatasvir 17% Daclatasvir 90 ./
Daclatasvir 120 . + EFV 600 .
RPV
DTG Daclatasvir
EGV/c Daclatasvir Daclatasvir 30 ./
RAL
Dasabuvir + Paritaprevir/ ATV ATV ATV 300 . Dasabuvir +
Ombitasvir/RTV Paritaprevir/Ombitasvir/RTV RTV
DRV DRV Cmin 43-48%
LPV/r Paritaprevir AUC 117%
EFV
ETR,NVP Dasabuvir,Paritaprevir/
Ombitasvir
RPV RPV AUC 150-225% QT prolong
DTG
EVG/c
Management of HIV-Infected Adult
LPV/r LPV/r 500/125 . ETR 30-45% LPV AUC 27% RPV AUC 52% RAL
12 . + EFV 600 .: LPV 13-20% Cmin 51% Cmin 74% LPV/r
LPV LPV/r LPV/r
400/100 . 12 .
EFV
LPV/r 500/125 . LPV/r 500/125 . +
12 . + EFV 600 . NVP 200 . 12 .
24 .
EFV ETR NVP RPV RAL
NVP NVP ETR -
EFV AUC 22%
-
RAL RAL AUC 36% ETR Cmin 17% -
RAL Cmin 34%
Management of HIV-Infected Adult
-
* LPV 7.3 ./ (LPV 1-4 ./) EFV, NVP LPV/r
LPV/r + EFV
3.8
3.14
3.14
anti-HBc, anti-HBs HBsAg
(hepatitis B)
HBsAg HBV Vaccine
anti HCV CD4 > 100 cells/mm3
(hepatitis C) ( CD4 )
-
2 neurosyphilis
1 MSM,
( 2-4
) Lumbar puncture failure to treatment,
ocular Syphilis tertiary
Syphilis CSF RPR neurosyphilis
110
Management of HIV-Infected Adult
111
CXR
CXR 14
2
*
1. (unexplained)
2. 1
3. 5 1
4. > 3 1
CXR AFB
* 2
CMV retinitis indirect ophthalmoscope
CD4 < 100 cells/mm3
serum cryptococcal Ag CD4 < 100
cells/mm3
Cryptococcus Ag positive LP
meningitis ( stiff neck + ve)
cryptococcus menigitis
Anti HIV +
CD4 < 100 cells/mm3
()
Negative
serum cryptococcal
antigen + *
Positive
lumbar
puncture**
10
uconazole 200 .
1 CD4 > 100 4-6 ***
cells/mm3 3
* primary prophylaxis
primary prophylaxis
** CT brain lumbar
puncture
112
Management of HIV-Infected Adult
113
( )
() LP cryptococcemia
fluconazole LP
cryptomeningitis IRIS
/ crypto-
coccal menigitis CSF cryptococcal
antigen serum cryptococcal Ag
cryptococcal meningitis (
serum antigen meningitis
disseminated disease serum antigen
CSF ) secondary prophylaxis
fluconazole 200 . CD4 > 100 cells/mm3 3
serum cryptococcal Ag
primary prophylaxis
cryptococcal capsular polysaccharide antigen serum
CSF latex agglutination (LA) enzyme immunoassay (EIA)
overall sensitivity 93-100% specificity 93-98% test
false positive (0-0.4%)
serum CSF
: cryptococcal antigen
rheumatoid factor ( LA serum specimen
CSF), non-specific protein CSF
autoimmune diseases, malignancy CNS involvement /
lymphoma/leukemia, ,
Trichosporon spp. false positive test titer 1:8
MSM transgender (TG)
Q2
Q9
Q2 Q9
()
RPV, NVP
EFV
6
pap smear
1 CD4
controversial standard protocol
MSM digital anorectal
examination anal pap 1-3
anoscopy
114
Management of HIV-Infected Adult
115
3.9
VL CD4 VL
CD4
3.15
adherence (stable
on ART) VL < 50 copies/mL 1
3-6
6
VL < 50 copies/mL
VL > 50 copies/mL > 200 copies/mL
VL 50-200 copies/mL
VL 3
VL 6 VL < 50
copies/mL 1
2-4 VL
CD4 CD4
CD4 < 350 cells/mm3 2
CD4 350 cells/mm3
VL > 50 copies/mL
VL < 50 copies/mL
2 CD4
3.10
2 NRTIs
AZT ddI NNRTIs PIs
CrCl
Child-Pugh score
3.16 3.17
116
3.16
eGFR CrCl (./)(1)
Hemodialysis
50 30-49 10-29 < 10
NRTIs
50-25 .
3TC 300 . 24 . 150 . 12 . 150 . 24 . 100 . 24 .(2) 50-25 . 24 .(2)
24 .(2) AD(3)
300 . 300 .
TDF(4) 300 . 24 . 300 . 48 .
2 7 AD(3)
AZT 200-300 . 12 . 100 . 8 . 300 . 24 .
15 .
d4T 30 . 12 . 30 . 12 . 15 . 12 . 15 . 24 . 15 . 24 .
24 . AD(3)
Management of HIV-Infected Adult
800/100 . 24 . (nave)
DRV
600/100 . 12 .
LPV/r 400/100 . 12 . HD
Integrase inhibitors
RAL 400 . 12 .
DTG 50 . 24 .
EVG/COBI/
150/150/300/200 . 24 . CrCl < 70 ./ CrCl < 50 ./
TDF/FTC
(1)
creatinine clearance:
50 CrCl < 50 ./ TDF
TDF TDF + boosted PIs creatinine clearance (Cockcroft-Gault
Equation) < 60 ./ TDF 300 . TDF 150 . TDF
TDF
eGFR 30 ./
3.17
Child-Pugh score
5-6 A 7-9 B 10 C
NRTIs
3TC
TDF
AZT
d4T
ddI
ABC 200 . 12 .
TDF/FTC
NNRTIs
EFV
NVP
ETR
RPV
EFV/TDF/FTC
RPV/TDF/FTC
PIs
ATV 300 . 24 .
RTV
boosting
DRV
LPV/r
Integrase inhibitor
RAL
EVG/COBI/
TDF/FTC
120
Management of HIV-Infected Adult
121
Child-Pugh score
1 2 3
Total bilirubin (./) <2 2-3 >3
(./) > 35 28-35 < 28
International normalized ratio (INR)
< 1.7 1.7-2.3 > 2.3
Prothrombin time
<4 4-6 >6
()
(ascites)
Encephalopathy* 1-2 3-4
: Encephalopathy
* 1:
2:
3: routable
4:
3.11
3
1) (life-threatening adverse effects)
2) (serious adverse effects)
3) (long-term adverse effects)
3.18
: lactate
Lactate ( > 5 mmol/L) NRTIs mitochondrial toxicities
Arterial pH ( < 7.0) ABC, TDF, 3TC, FTC
Serum CO2 serum lactate
Anion gap NRTI-sparing regimens
ALT, AST, prothrombin time, bilirubin , albumin boosted PIs + NNRTI LPVr + EFV (
amylase lipase LPV/r 500/125-600/150 . 12
Histology microvesicular . EFV 600 . 24 .)
macrovesicular steatosis
/
Lactic acidosis, rapidly d4T d4T
progressive ascending
neuromuscular weakness
supportive care
d4T ascending lactic
demyelinating acidosis
polyneuropathy
Guillain-Barr plasmapheresis, high
syndrome dose steroid, IVIG,
carnitine
Management of HIV-Infected Adult
:
Serum lactate, anion gap
Arterial pH, serum CO2
Creatine phosphokinase
HSR ABC
3
Bone marrow suppression 2-3 Advanced HIV AZT AZT NRTI
AZT G-CSF
AZT neutropenia
1.1-4.0% neutropenia erythropoietin
neutropenia 1.8-8.0%
CBC
anemia
3-6 (
neutropenia cotrimoxazole, ribavirin, folic acid supplement
HBV
PIs
/
Nephrolithiasis, 1.5- IV fluid
urolithiasis, crystalluria nephrolithiasis 2
/
IDV 12.4% pyuria, hematuria, crystalluria peak IDV urinalysis serum
(4.7-34.4%) creatinine IDV creatinine 3-6 IDV
ATV, EFV
Nephrotoxicity TDF
TDF ATV serum creatinine,
nephrogenic diabetes insipidus
Management of HIV-Infected Adult
ddI TDF
ddI
hypertriglyceridemia
Bleeding episodes 2-3 PIs NNRTI Factor VIII
increase in hemophiliac hemophilia regimen
patients
PIs
/
3) (long-term adverse effects)
Lipodystrophy baseline BMI LPV/r
lipoatrophy ATV/r
Lipohypertrophy Lipohypertrophy injectable poly-L-lactic visceral fat
PI acid
NNRTI-based regimens
lipohypertrophy
d4T AZT (dorsocervical lipohypertrophy recombinant human
fat pad buffalo growth hormone
Lipoatrophy hump) GH-releasing hormone
NRTIs d4T Lipoatrophy restorative analogue
AZT,
ddI TDF,
ABC
Hyperlipidemia PIs NNRTIs cardiac risk
factors
Management of HIV-Infected Adult
PIs ( PIs LDL, TC
d4T lifestyle
unboosted ATV) 47- TG - PIs: RTV-boosted PIs fasting lipid profile modifications
75% HDL ATV, ATV/r 3-6 simvastatin
NRTIs NNRTIs DRV, LPV, SQV LDL, atorvastatin
PIs > NNRTIs boosting RTV TG
EFV > NVP d4T TG, LDL TC rhabdomyolysis
d4T > AZT > ABC > EFV, NVP LDL, TC,
TDF TG HDL EFV
3.12 ()
PIs 1.7-2.3
National Cholesterol Education Program,
Adult Treatment Panel III (NCEP ATP III)
10 Framingham
LDL 3.1
10 10
LDL-C 80
./
(lifestyle modification)
primary secondary
coronary prevention statin
LDL
3.1 LDL
134
3.1
10 1
10 20%2
Management of HIV-Infected Adult
HbA1C < 6.5-7.0% 3 (mg/dL)
4
SBP < 130 mmHg SBP < 140 mmHg 155 190
DBP < 80 mmHg DBP < 90 mmHg LDL 80 115
:
1. 10
10 Framingham www.cphiv.dk/tools.aspx
2.
. Boosted PIs RPV, NVP, RAL Boosted PIs
. d4T, AZT TDF ABC
3.
LDL
> 400 ./ LDL [ LDL =
TC - HDL - (TG/5)] LDL 30 ./
4.
> 1,000 ./
3.19
PI
NNRTI
Statin Atorvastatin 10-80 ./ 1 2
( 40 ./)
Fluvastatin 20-80 ./ 2 2
Pravastatin 20-80 ./ 2,3 2
Rosuvastatin 5-40 ./ 1 1
( 20 ./)
Simvastatin 10-40 ./ 2
Pitavastatin 1-4 ./
Cholesterol Ezetimide 10 ./
uptake
:
1. statin statin
2. statin statin statin
136
Management of HIV-Infected Adult
137
3. DRV/r pravastatin
pravastatin metabolism CYP450
. atorvastatin
atorvastatin 10-20 ./ pitavastatin
statin
pravastatin
3.13
(Adherence to antiretroviral therapy)
adherence
adherence
adherence
1 adherence
adherence
IRIS
138
Management of HIV-Infected Adult
139
3.21 IRIS
Tuberculosis paradoxical reaction
38.5oC, , ,
cutaneous lesions, ascites, CXR worsening, tuberculoma, inflammatory
bowel perforation, serositis, psoas abscess
MAC Localized lymphadenitis, necrotizing subcutaneous nodules,
atypical mycobacteria endobronchial tumors, small bowel involvement, paravertebral
abscesses, osteomyelitis, arthritis, focal brain lesion, ileitis
CMV CMV retinitis CD4 , immune recovery vitreitis,
immune recovery uveitis, CMV pneumonitis
, pseudotumoral colitis,
adenitis, encephalitis, cutaneous ulceration
Hepatitis (B,C)
Parvovirus B19 Encephalitis, worsening anemia
Herpes simplex Erosive herpes simplex encephalitis
Varicella zoster virus Acute retinal necrosis ,
Kaposi's sarcoma (KS) Worsening KS lesion with inflammation and edema
PML Inflammatory PML variant
BK virus Hemorrhagic cystitis
Cryptococcus Recurrent meningitis , pulmonary cryptococcosis,
cutaneous cryptococcosis (recurrent abscesses), necrotizing mediastinal
cervical lymphadenitis, intracranial cryptococcoma, intramedullary
abscess, necrotizing pneumonitis
PCP Pneumonitis (patchy aveolar or reticulonodular infiltrates)
Skin yeasts Folliculitis
Sarcoidosis Worsening of sarcoidosis, pulmonary infiltrates, erythrema nodosum,
lymphadenopathy, interstitial nephritis
Toxoplasmosis Encephalitis
Leishmaniasis Vitreitis, uveitis, post-kala-azar dermal leishmaniasis
Bartonella henselae Granulomatous splenitis
Leprosy Leprosy cutaneous lesions
Microsporidia Keratoconjunctivitis
Chlamydia trachomatis Reiters syndrome
Non infectious etiology Grave diseases, SLE, vasculitis, relapsing Guillain-Barres syndrome,
rheumatoid arthritis, polymyositis, alopecia universalis, cerebral
vasculitis, hyperergic reaction ( ),
pre-eclampsia, multiple eruptive dermatofibromas, eruptive cheilitis,
Peyronies disease
3.22 IRIS
Paradoxical IRIS
IRIS
1.
2. 1
1
Unmasking IRIS
IRIS
1.
2.
140
Management of HIV-Infected Adult
141
Unmasking IRIS ()
3.
3
3.15
142
Management of HIV-Infected Adult
143
3.15.2
> 40 30-50
1-4
HIV/HBV co-infection
TDF, FTC 3TC
3.24 3.25
144
Management of HIV-Infected Adult
145
3.25
/
HIV Backbone: TDF/FTC TDF + 3TC
3TC FTC TDF
HBV
FTC, 3TC hepatic
TDF flare
entecavir ( 3TC
entecavir 1 ./) hepatic flare
HIV FTC, 3TC TDF, 3TC
TDF FTC
TDF FTC 3TC d4T
TDF AZT TDF HIV RNA < 50 copies/mL
HIV/HBV HIV/HBV TDF/FTC TDF + 3TC
tenofovir HBsAg HBsAg
CrCl < 30 ./ 10-20 HIV/HBV
tenofovir HBsAg tenofovir
HBsAg HBV DNA < 2,000 IU/mL
entecavir HBV DNA
TDF/FTC TDF/3TC > 3
HBV TDF
HBV 3TC HBV
boosted PI + 3TC
TDF abacavir
HIV LPV/r + 3TC ARV
nave (GARDEL study) ARV experience HIV
RNA < 50 copies/mL (OLE study) ATV/r + 3TC
ARV experience HIV RNA < 50 copies/mL (SALT
study)
AZT d4T VL < 50 copies/mL
TDF
/
1. FTC, 3TC TDF eGFR
3.16
2. TDF entecavir entecavir
HBV 3TC
CrCl > 50 ./, entecavir 0.5 ./
CrCl 30 - < 50 ./, entecavir 0.25 ./ 0.5
. 48 .
< 30 ./, entecavir 0.15 ./ 0.5 .
CrCl
72 .
CrCl < 10 ./, hemodialysis, CAPD, entecavir 0.05
./ 0.5 . 7
HBV 3TC/decompensated liver disease
CrCl > 50 ./, entecavir 1 ./
CrCl 30 - < 50 ./, entecavir 0.5 ./ 1 .
48 .
< 30 ./, entecavir 0.3 ./ 1 . 72
CrCl
.
CrCl < 10 ./, hemodialysis, CAPD, entecavir 0.1 ./
1 . 7
3. TDF
ABC
4. HIV RNA <50 copies/mL
LPV/r + 3TC ATV/r + 3TC
> 40 > 50
liver ultrasound
HIV/HCV co-infection
3 45-50
pegyrated interferon/
ribavirin 1 30-35
pegyrated interferon/ribavirin
146
Management of HIV-Infected Adult
147
3-6
Direct acting antiviral (DAA)
(extrahepatic manifestation)
95 3
24-48
8-12 20-24
anti HCV 3.26-3.31
3.26 anti-HCV
anti-HCV
HCV RNA
anti-HCV
HCV RNA
spontaneous clearance
HCV RNA
liver fibrosis
(LFT) APRI, FIB-4
ultrasound /
(liver stiffness) transient elastography
HBsAg, anti-HBc HAV Ab
(HCV genotype)
acute
anti-HCV HCV HCV RNA
HCV RNA
CD4 HCV RNA 6
< 100 cells/mm3 3.2
(crystal metamphetamine) spontaneous
clearance
HCV RNA
anti-HCV
CD4 100 cells/mm3
3.2 anti-HCV
Anti HCV Ab
positive
HCV RNA
148
Management of HIV-Infected Adult
149
MSM IDU
(reinfection) 30-40
3.28 DAA
Sofosbuvir HCV NS5B inhibitor nucleotide metabolize cytochrome
polymerase inhibitors P450 enzyme p-
glycoprotein transporter
Ledipasvir HCV NS5A inhibitor TDF TDF
sofosbuvir + TDF
ledipasvir boosted PIs tenofovir
sofosbuvir/ledipasvir toxicity
400/90 ./ (1 1 )
CrCl < 30 ./
HCV genotype 1, 2, 4,
5, 6 3
60-70%
Dasabuvir
ombitasvir (NS5B inhibitor)
(NS5A inhibitor), Paritaprevir substrate CYP3A4
paritaprevir inhibitor CYP3A4 enzymes ATV RTV
(HCV PI)/RTV dasabuvir metabolized
CYP2C8 enzymes
ombitasvir,paritaprevir,dasabuvir
UGT1A1
substrates P-gp
150
Management of HIV-Infected Adult
151
Daclatasvir HCV NS5A inhibitor p-glycoprotein transporter
sofosbuvir
EFV, ETR, NVP
12
24 daclatasvir daclatasvir
90 ./
ribavirin ATV/r
daclatasvir daclatasvir daclatasvir
60 . (1 1 ) 30 ./
HIV/HCV
HCV
EFV RPV
ATV/r LPV/r
(ATV/r)
daclatasvir 30 ./
Elbasvir genotype 1, 4 p-glycoprotein
(NS5A inhibitor)/ 1 transporter
grazoprevir
(HCV PI) EFV
Sofosbuvir NS5B inhibitor/ p-glycoprotein
Sofosbuvir/ velpatasvir NS5A inhibitor transporter
velpatasvir genotype
1 EFV
tenofovir
tenofovir toxicity
CrCl < 30 ./
2559 pegylated
interferon, ribavirin, sofosbuvir, daclatasvir pegylated interferon,
ribavirin 2559 pegylated interferon/ribavirin + sofosbuvir 12
Daclatasvir + sofosbuvir 3 sofosbuvir/ledipasvir
3
3.29 pegylated
interferon
*
18 (decompensated cirrhosis)
> 6
HCV RNA 5,000 interferon ribavirin
IU/mL
3
HIV RNA < 50 copies/mL
* - pegylated interferon/ribavirin
- AZT, d4T ddI
ribavirin
152
3.30
DCV/SOF LDV/SOF SOF/RBV DCV/SOF DCV/SOF/RBV LDV/SOF LDV/SOF/RBV SOF/RBV
Genotype 1 12 12 * 24 12 24 12 **
Genotype 2 12 16
Genotype 3# 12 24 24
Genotype 4 12 12 24 12 24 12
Genotype 5 12 24 12
Genotype 6 12 24 12
Management of HIV-Infected Adult
* 8 nave, HCV RNA < 6 million/IU/mL, no cirrhosis
** < 75 x 103 IU/uL, RBV 24
# AASLD/IDSA guideline July 2016: SOF/DCV SOF/VEL 12 HCV genotype 3, non cirrhosis SOF/VEL SOF/DCV+/-
RBV 24 HCV genotype 3, compensated cirrhosis SOF/VEL SOF/DCV+RBV (low dose) 12 HCV genotype 3,
compensated cirrhosis
: DCV/SOF-Daclatasvir/Sofosbuvir, SOF/VEL-Sofosbuvir/Velpatasvir, LDV/SOF-Ledipasvir/Sofosbuvir, SOF/RBV-Sofosbuvir//Ribavirin
Genotype 4 12 12 24 12 a 24
Genotype 5 12 12
Genotype 6 12 12
a. genotype 1a Q80K Sim/SOF
b. genotype 1a: Ombitasvir/Paritaprevir/RTV/dasabuvir ribavirin
genotype 1b: Ombitasvir/Paritaprevir/RTV/dasabuvir
Management of HIV-Infected Adult
155
3.15.3
50
1.
(
CD4)
2. (pharmacokinetic)
> 40 glomerular
filtration rate 1 .
CrCl Child-Pugh class
3.
albumin
CYP450
AZT
TDF PIs
4.
3.32
3.32
d4T, ddI AZT
NVP, EFV boosted ATV/r DRV/r
PIs
ABC, ddI, LPV/r
TDF TDF
ATV
ATV
NVP
boosted PIs, d4T ddI
d4T
ddI non-cirrhotic
portal hypertension
156
Management of HIV-Infected Adult
157
TDF
ATV/r EFV
EFV EFV
Cognitive impairment
5.
6.
2
2
2
5
EFV
EFV
3.15.4
(MSM) (TG)
adherence
(retention)
MSM TG
/
/
MSM TG
3
6
(cardiovas-
cular disease)
TG
158
Management of HIV-Infected Adult
159
() erectile
dysfunction
(digital rectal examinations)
(
fosampinavir ampinavir
)
adherence
DMPA
3.12
TG
/ /
MSM
TG
3
160
Management of HIV-Infected Adult
161
3.15.5
2
(AIDS-related malignancies)
Kaposi sarcoma Non-Hodgkins (Non-Hodgkins
lymphoma)
(primary central nervous system lymphoma)
2 (non-AIDS-related malignancies)
(oncogenic virus) human
herpes virus (HHV) 8, Ebstein-Barr virus (EBV), human
papillomavirus
2 2
/
CD4 VL
CD4
CD4 200 cells/mm3
CD4 < 200 cells/mm3
162
Management of HIV-Infected Adult
163
()
/
CD4
(drug-
drug interaction)
protease inhibitors
taxanes, vinca alkaloids, etoposide
gefitinib
AZT
d4T ddI peripheral neuropathy
3.15.6
3.33
3.33
VL 2-3
NNRTIs NNRTIs boosted PIs
(elective) 10-14
NNRTIs 7-10
NRTIs
PIs
164
Management of HIV-Infected Adult
165
3.15.7
methadone
HCV
methadone
adherence HIV/HCV
coinfection 3.15.2
methadone 3.34 1
NVP methadone 50% methadone
withdrawal
methadone
ETR
RPV
Integrase strand transfer inhibitors (INSTIs)
RAL
DTG
EVG/COBI
* R-methadone = active form methadone
3.15.8
TDF
proximal tubular dysfunction persistent proteinuria
[urine dipstick > 1 urine protein/creatinine (UP/C) > 30 mg/mmol],
glycosuria eGFR
phosphaturia
TDF
TDF (vi)
Fanconi syndrome TDF Assessment:
Tests for proximal renal tubulopathy/renal
Fanconi syndrome(iii)
Consider renal bone disease
hypophosphataemia :
25(OH) vitamin D, PTH, DXA
166
Management of HIV-Infected Adult
167
TDF (vi)
Proximal tubulopathy with any combination TDF :
of: Progressive decline in eGFR
1. Proteinuria: urine dipstick 1,
urine protein/creatinine (UP/C) Confirmed hypophosphataemia
> 30 mg/mmol, glycosuria
(i) Osteopenia/osteoporosis
2. Progressive decline in eGFR and eGFR urine phosphate leak
< 90 mL/min(ii) eGFR
3. Phosphaturia(iii): confirmed hypophospha-
taemia secondary
phosphate
3.35 TDF
HIV
glomerular function
tubular function eGFR 6 UA 1
eGFR HIV
> 60 ml/min/1.73 m2 Protease inhibitor, ,
proteinuria, ,
normoglycemic glucosuria
phosphaturia NSAIDs
eGFR, UA
phosphorus 6
HIV
proteinuria / TDF
eGFR 60 ml/
min/1.73 m2 TDF
eGFR
eGFR
proteinuria
TDF
TDF
proteinuria
TDF
1 3
TDF
2 TDF
TDF eGFR
proximal dysfunction
dose TDF
eGFR / eGFR
proximal proximal dysfunction
dysfunction eGFR
Bone demineralization
TDF proximal tubular dysfunction
proteinuria, normoglycemic glucosuria phosphaturia
phosphorus
168
Management of HIV-Infected Adult
169
HIV
proteinuria normoglycemic
glucosuria phosphaturia fractional excretion
phosphorus proteinuria
normoglycemic glucosuria phosphorus presumptive
diagnosis TDF
proximal tubular dysfunction TDF
eGFR TDF
eGFR proximal
tubular dysfunction
1 3
6
eGFR Cr 6 UA
1 *
2
1 3
Cr (optional)
(optional)
eGFR proteinuria 1+
normoglycemic glycosuria
TDF TDF
1
TDF
TDF
1-2
1-3 Cr
(optional)
eGFR
proteinuria normoglycemic
glycosuria TDF
(hemodialysis, HD), (peritoneal dialysis, PD)
(kidney transplantation, KT)
ESRD
170
Management of HIV-Infected Adult
171
(standard infection control)
1.
2.
3.
CDC
sterilization
4. ultrafiltrate
ultrafiltrate
ultrafiltrate
ultrafiltrate
:
(dialyzer)
(blood line)
(benzalkonium chloride)
heparin
172
Management of HIV-Infected Adult
173
3.16
CD4
CD4
3.36
(live-attenuated vaccine)
measles, mumps, varicella zoster yellow fever
3.36
Hepatitis A 2 :
vaccine HAV (MSM)
(HAV) ( HBV/HCV) clotting factor
concentration HAV
serum HAV IgG
2 : 2 6-12
Hepatitis B 3 HBV HBsAg,
vaccine anti-HBs, anti-HBc
(HBV) 3 : , 2 1 , 3
2 2 4
( 2 3 1 6 )
anti-HBs 3 1
anti-HBs < 10 IU/L 1
anti-HBs 1
2
anti-HBs 1
CD4 < 350 cells/mm3
Human 3 HPV 4 (quadrivalent)
papillomavirus 9-26
vaccine (HPV) 19-26 MSM
HPV
(anal cancer)
Influenza
1
nasal spray
Tetanus and 1 1 10
diphtheria Tetanus, diphtheria and pertussis (Tdap) Td
toxoid (Td) TT 1
Tetanus
Toxoid (TT)
23-valent 1 CD4 > 200 cells/mm3
pneumococcal 1 5
polysaccharide 65 65
vaccine PCV-13 PPSV-23
(PPSV-23) 1
174
Management of HIV-Infected Adult
175
13-valent 1 CD4 > 200 cells/mm3
pneumococcal
conjugate PPSV-23 PCV-13
vaccine 2
(PCV-13)
Rabie vaccine 5 2 rabies
neutralizing antibody
()
19-27 27-64 65
Influenza
Tetanus,diphtheria,pertussis (Td/TT/Tdap) 1 Td ( TT) 10
Td (or TT) Tdap 1
(Varicella)
(HPV) 3
(0, 2, 6 )
(HPV) 3
Measles, mumps, rubella (MMR)
PCV13 1 1 ( > 50 )
PPSV-23 1 1 1
Meningococcal*
(hepatitis A) 2
:
HAV
( HBV/
HCV) clotting factor concentration
HAV
serum HAV IgG
(hepatitis B) 3
HBV
HBsAg, anti-HBs, anti-HBc
2
(optional vaccine)
*
10
(meningitis belt)
(anatomic functional asplenia)
4
(Management of HIV-Infected Children and Adolescent)
1. 18
2.
HIV DNA
PCR
HIV DNA PCR 4 , 1, 2
4
HIV DNA PCR 2
1 2-4
3. HIV DNA PCR
HIV DNA PCR HIV RNA
viral resistance
AZT + 3TC + LPV/r HIV DNA PCR
HIV DNA PCR
HIV DNA PCR
4. 18
5.
< 1 1-< 5 5-15
WHO WHO
stage 3,4 stage 3,4
CD4 CD4 < 500 cells/mm3
1-3 CD4 < 25
CD4 < 1,000 cells/mm3
3-< 5 CD4
< 25 CD4 < 750
cells/mm3
6. 4.6
< 3 3-12 > 12
AZT ( ABC) + AZT ( ABC) + TDF + 3TC (FTC) +
(preferred regimens) 3TC + LPV/r 3TC + EFV EFV
AZT ( ABC) + AZT ( ABC) + AZT ( ABC) +
(alternative regimens) 3TC + NVP 3TC + NVP 3TC + EFV
TDF + 3TC (FTC) + TDF + 3TC (FTC) +
EFV ATV/r
TDF + 3TC (FTC) + TDF + 3TC (FTC) +
NVP RPV
7. 1
4.7
8. drug interaction
rifampin efavirenz
2-8
178
Management of HIV-Infected Children and Adolescent
179
9.
CD4 6 > 5
plasma HIV Viral load < 50 copies/ml, CD4 > 500 cells/mm3
CD4
10.
4.7
11.
(Transition to adult clinic) 4.14
12.
CD4
< 12 1-5 6-12
CD4 count CD4 count CD4 count
CD4 CD4 CD4
1: 1,500 34 1,000 30 500 26
5,000
2557 2.1
100
18
( 2 2.1
)
180
Management of HIV-Infected Children and Adolescent
181
4.1
PCP 4-6
Isoniazid
HIV DNA PCR
HIV DNA PCR
HIV DNA PCR 4 1, 2
4
HIV DNA PCR 2
1 2-4
4.1.1
5
4.1.2
AZT
CBC 1
Pneumocystis
jiroveci (PCP)
1)
CD4 > 25
CD4 15
6
CD4 > 15
CD4
2)
immunoglobulin (TIG)
(RIG)
4.1
182
4.1
.. 2559
1 2 4 6 9 12 18 2 2 4-6 11-12
1 BCG
2 HBV1 (HBV2) DTwP- DTwP- DTwP-
HBV1 HBV2 HBV3
--3 DTwP DTwP DT
1 2
4 OPV1 OPV2 OPV3 OPV or OPV or
or or or IPV IPV
IPV IPV + IPV 1 2
Management of HIV-Infected Children and Adolescent
10 (influenza) 6
1.
1) BCG
BCG
BCG
2) 0.1 .
3)
4)
2.
1) 3 6
2) HBsAg 3 1-2
6 1
12 . 2 3 1 6
3) HBsAg ( HBeAg )
HBIG 0.5 . 12 . 1
HBIG
a. HBIG 2 1-2 3 6
b. HBIG 1 12 . 2
1 3 6
4) HBsAg HBIG
7
5) -
-- (DTP-HB) 2, 4, 6 HBsAg
HBIG 1
( 5 )
6) HBsAg HBsAg anti-HBs
9-18
3. --
1) (DTaP) (DTwP)
2) DTaP 2, 4, 6
3) 18 DTwP DTaP
4) 4-6 DTwP, DTaP Tdap
5) 11-12 Td Tdap Tdap 4-6
Td 10
4.
1) IPV OPV IPV
2) OPV 5 IPV
1 4 trivalent OPV bivalent OPV
2559
3) 4
18
5. --
-- (clinical stage C
CD4 < 15) CD4 > 15
1) 9-12 2
2 12 2
4-6
2) 6
2 2 3
9 2 12 3 2
3) --
--- (MMRV)
1-12 MMRV 2-6
MMRV
12-23
MMR VZV MMRV MMR
1 VZV 3
6.
3 1 0, 1 , 1
1 3 4-5
(
6 CD4 > 15% 2 3-12
)
1) (Inactivated vaccine) 2 mouse-brain derived
vaccine (MBV) P3 vero
cell (JEVACTM) 3 9-18 4
1 MBV 3
4-5
186
Management of HIV-Infected Children and Adolescent
187
Inactivated JE live-attenuated JE
1 2 3-24 ()
2-3 1 1
4 *
* Live JE 1 1
3) Live JE 1 Inactivated JE
1 12
7.
conjugate PRP-T 2
3 2, 4 6 1 12-18
2
PRP-T
2-6 0, 2, 4, Booster
7-11 0, 2, Booster
12-59
Booster 12-18 2
8.
1 2 6-12
9.
1 CD4 > 15 2
1 2 4-6 2 4
3 > 13
1
10.
1) 6 18
< 2
2) < 9 1
3) < 3 0.25 0.5 . ()
4) 3 4
11.
10 (PCV10) 13 (PCV13) 3 2, 4
6 12-15 2
PCV PS-23
2 PCV 2 PS-23
1 5
2- 7 PCV 3 6-8 PCV 1 12-15
7- 12 PCV 2 6-8 PCV 1 12-15
12-23 PCV 2 6-8
2-5 PCV 10 2 PCV 13 1
2- 6 PCV13 2 8 PS-23 1
> 6-18 PCV13 1 PCV 8
: PCV = Pneumococcal conjugate vaccine, PS-23 = 23-Valent pneumococcal polysaccharide
vaccine PCV13
2 PS-23
PCV PS-23 1 5
PCV PS-23 PS-23
PS-23 PCV
12.
1) monovalent 2 2 4
2) pentavalent 3 2, 4 6
3) 6-15
8 4
188
Management of HIV-Infected Children and Adolescent
189
4)
3
5)
6) severe combined immune deficiency (SCID)
13.
1) 2 2 (bivalent 16, 18) 4 (quadrivalent
6, 11, 16, 18)
2) 9-26 ( 11-12 ) 3
0, 1-2, 6
3)
4) > 26
5) 4 9-26
11-12 9-26
1)
2)
4.2 4.3
CD4 > 15 > 200 > 5
CD4 < 15
6
CD4 > 15
CD4
CD4
Thailand National Guidelines on HIV/AIDS Treatment and Prevention 2017
2560
4.2 1-6
1 0 DTP-HB1, OPV/IPV1, MMR
2 1 JE1
3 2 DTP-HB2, OPV/IPV2, JE2
4 4 DTP-HB3, OPV/IPV3
5 12 DTP-HB4, OPV/IPV4, JE3
4.3 7-18
1 0 dT1, OPV/IPV1, MMR
2 1 HBV1, JE1
3 2 dT2, JE2, OPV/IPV2, HBV2
4 7 HBV3
5 12 dT3, OPV/IPV3, JE3
( 6)
PCP
PCP 2-3
6 CD4 15 PCP
CD4
PCP Co-trimoxazole
(TMP-SMX) 150 mg/m2 TMP 1-2 3
TMP/SMX
46 PCP
190
Management of HIV-Infected Children and Adolescent
191
12 > 12
CD4 < 15
15 TMP/SMX dapsone
2 ./. ( 100 .) 4 ./. ( 200 .)
desensitization TMP/SMX
PPD
skin test isoniazid 10 ././ (
300 .) 9
10-15
PCP
PCR (
2 5)
1. HIV DNA PCR
1.1 ( HIV RNA
> 50 copies/mL HIV RNA
< 12
) HIV
DNA PCR 4 , 1 , 2 4
HIV DNA PCR
4-6
(AZT/3TC/NVP) (AZT/3TC/LPV/r)
( 4.7)
1.2 HIV DNA PCR
() HIV DNA PCR 2 1
2-4 HIV DNA PCR
HIV DNA PCR
(AZT/3TC/LPV/r) HIV DNA PCR
HIV DNA PCR
HIV DNA PCR
50-60 HIV DNA PCR
HIV DNA PCR
4-6 HIV DNA PCR 2 1
2-4 ( > 4
)
192
Management of HIV-Infected Children and Adolescent
193
3 HIV DNA PCR
(dried blood spot)
whole blood
HIV DNA PCR 1 2
4
HIV DNA PCR
194
4.4
HIV DNA PCR HIV Ab
1 2 4 18
-ve N/A N/A N/A N/A HIV PCR
-ve -ve -ve N/A N/A : HIV PCR
: 4
4
-ve -ve -ve -ve N/A :
18-24
:
24
-ve -ve -ve -ve +
: HIV DNA PCR
Management of HIV-Infected Children and Adolescent
+ve +ve N/A N/A N/A
-ve +ve +ve N/A N/A
-ve -ve +ve/+ve N/A N/A
-ve -ve -ve +ve/+ve N/A HIV DNA PCR
4.3
(ARV therapy in na ve HIV-infected children)
1
> 1
WHO stage 3, 4)
CD4
1-5 CD4 < 25 CD4 < 1,000 cells/mm3
3-< 5 CD4 < 25 CD4 < 750 cells/mm3
5-15 CD4 < 500 cells/mm3
CD4
CD4 6
< 3 : 2NRTIs + Boosted PI (LPV/r)
3 : 2NRTIs + NNRTIs
2 NRTIs
12 AZT/3TC ABC/3TC
> 12 TDF/3TC (FTC)
NNRTIs boosted PI
3 boosted PI LPV/r
> 3 NNRTIs EFV
(Adherence) boosted
PI Atazanavir/r
4.3.1
1. (medical evaluation)
1.1) (co-infection) (opportunistic
infections) Immune
reconstitution inflammatory syndrome (IRIS)
CXR
PPD skin test
latent TB infection
HBs Ag
HBs Ag NRTIs
Tenofovir Lamivudine Emtricitabine
anti-HCV
cytomegalovirus (CMV)
CMV (CMV retinitis) < 5 CD4 5
CD4 < 50 cells/mm3 6
floater
198
Management of HIV-Infected Children and Adolescent
199
1.2) CD4
2
Co-Trimoxazole
Adherence Co-Trimoxazole
1.3)
NNRTIs
1.4)
CBC, differential count
CD4 CD4
CD4
ALT, AST
Tenofovir (TDF) urine analysis
glycosuria, proteinuria BUN, creatinine
estimated GFR (eGFR)
2. (ARV counseling)
2.1)
2.2) ( 6 )
2.3)
200
Management of HIV-Infected Children and Adolescent
201
2.4)
2.5) (adherence
counseling) 4.14
4.3.2
1. CD4 < 1
10-15
1
CD4
> 1
CD4
CD4 1-5 CD4 > 25
5-15 CD4 > 500 cells/mm3
CD4 6
CD4
2.
2
2.1 CDC surveillance classification system .. 2537
category N, A, B C .. 2557
HIV infection stage 1,2,3 stage 1, 2
CD4 stage 3
AIDS CD4
CDC stage 3
2.2 WHO staging system .. 2549 WHO stage 1, 2, 3
4 WHO stage 3 4
WHO stage 1, 2 7
20 WHO stage 3 4
3. (Behavioral- risk HIV-infected
adolescents)
(Treatment as Prevention)
adherence
4.5 .. 2559
< 1 1 - < 5 5 -15
WHO stage 3, 4 WHO stage 3, 4
CD4 CD4 < 500 cells/mm3
1-3 CD4 < 25
CD4 < 1,000 cells/mm3
3-< 5 CD4 < 25
CD4 < 750 cells/mm3
WHO stage
1
WHO stage 1, 2 CD4
CD4 6
202
Management of HIV-Infected Children and Adolescent
203
4.3.3
(antitretroviral na ve)
4.6
4.6
< 3 3-12 > 12
AZT1 ( ABC2) + 3TC AZT1 ( ABC2) + 3TC TDF5+ 3TC (FTC) + EFV
(preferred + LPV/r3 + EFV
regimens)
AZT1 ( ABC2) + 3TC AZT1 ( ABC2) + 3TC AZT1 ( ABC2) + 3TC
(alternative + NVP4 + NVP4 + EFV
regimens)
TDF5 + 3TC (FTC) + EFV TDF5 + 3TC (FTC) + ATV/r6
TDF5 + 3TC (FTC) + NVP4 TDF5 + 3TC (FTC) + RPV7
1
(Hb < 8-9 g/dL) stavudine (d4T) 6
AZT
2
Abacavir (ABC) hypersensitivity ()
HLA-B*5701 HLA-B*5701
4.0
HLA-B*5701
6
3
Lopinavir/ritonavir (LPV/r) 14 42
post conceptional age Lopinavir propylene glycol
4
NVP AZT + 3TC + NVP (GPO-VIR Z250)
lead-in 2
2
5
Tenofovir (TDF) 2
35 tenofovir/
emtricitabine (TDF/FTC) TDF + 3TC
6
Atazanavir/r boosted PI
Efavirenz
NNRTIs NNRTIs
7
Rilpivirine (RPV) NNRTIs
EFV EFV VL >100,000 copies/mL
HIV RNA Rilpvirine HIV RNA
CD4 > 350 cells/mm3
> 12 > 35
4.7 1
AZT 3TC LPV NVP *
(10 mg/mL) (10 mg/mL) (80 mg/mL) (10 mg/mL)
(kg) 180-240 mg/m2 4 mg/kg 300 mg/m2 200 mg/m2
12 . 12 . 12 . 12 .
> 3-4 . 4 mL 1.5 mL 1 mL 5 mL
> 4-5 . 5 mL 2 mL 1 mL 5 mL
> 5-6 . 6 mL 2.5 mL 1.2 mL 6 mL
> 6-7 . 7 mL 3 mL 1.4 mL 7 mL
> 7-9 . 8 mL 3.5 mL 1.6 mL 9 mL
> 9-11 . 9 mL 5 mL 1.6 mL 10 mL
12-15 . 12 mL 5 mL 1.8 mL 12 mL
* (
5.7)
* LPV/r NVP
*
(Body Surface Area) = () x ()
3600
204
Management of HIV-Infected Children and Adolescent
205
4.3.4
3
3 AZT/3TC/NVP 6
HIV DNA PCR 1
HIV DNA PCR plasma
HIV RNA HIV viral resistance
AZT/3TC/LPV/r HIV
DNA PCR AZT 3TC
4.7 HIV DNA PCR
HIV DNA PCR 1
6
HIV DNA PCR 2 2
4 HIV DNA PCR 3
HIV DNA PCR
AZT/3TC/LPV/r
( 4.8)
4.3.5
(antiretroviral therapy in children with opportunistic infection)
drug interaction
rifampin efavirenz, nevirapine ritonavir
boosted PI Efavirenz
2-8 boosted PI
rifampin
quinolone aminoglycoside rifampin
2-8 Immune reconstitution inflammatory
syndrome (IRS) CD4 CD4
Cryptococcus Cytomegalovirus (CMV) IRIS
CD4
Crytococcus antigen
(drug interaction)
IRIS
CD4
CD4 IRIS
19 4
2
tuberculosis (TB), Non tuberculous Mycobacterium (NTM) Mycobacterium
avuim intracellularae complex (MAC), Pneumocystis jiroveci (PCP), cryptococcosis,
cytomegalovirus (CMV) cryptosporidiosis,
206
Management of HIV-Infected Children and Adolescent
207
microsporidiosis, JC virus
2-8
CD4 /
2-4
4-8
> 5 CD4
( 6)
< 5
CD4 5 CD4 < 50 cells/mm3
5
floater
IRIS CMV
CD4
2-8
Adherence
rifampicin
NNRTIs PIs
EFV, NVP ritonavir-boosted PIs
1)
2
CD4
2-4 CD4
8 2
2)
3 2 NRTIs NVP
3 2NRTIs + EFV
ritonavir boosted PIs
rifampicin
CD4 (<15%)
rifampicin quinolones
aminoglycoside PIs
CD4
rifampicin 2
maintenance rifampicin PIs
PIs rifampicin 2 (
rifampicin )
NNRTIs
NVP
PIs ( NNRTIs)
CD4 (>15%) PIs
PIs rifampicin 2
208
Management of HIV-Infected Children and Adolescent
209
PIs maintenance
rifampicin quinolones
aminoglycoside CD4 (<15%)
rifampicin PIs
3.3
(immune tolerance)
tenofovir (TDF), lamivudine (3TC)
3TC
3TC 20
TDF 3TC (FTC)
TDF > 2
3TC
TDF TDF
TDF 3TC (FTC)
(hepatic flare)
4.4
Plasma HIV Viral load
6 6-12
CD4
6
> 5 plasma HIV Viral load < 50 copies/mL,
CD4 > 500 cells/mm3
CD4
4.4.1
2-3
2-3
1) (new clinical events)
IRIS
2) (secondary
sex characteristics)
3) (neurodevelopment)
2
210
Management of HIV-Infected Children and Adolescent
211
4.4.2
1) (safety monitoring)
1.1) CBC 6 AZT
3 WBC
1.2) Chemistry liver enzymes (ALT), lipid profiles (cholesterol
triglycerides), serum creatinine fasting blood sugar 6
NVP ALT 2-4
1.3) Urine analysis 6 TDF
2) (immunological virological monitoring)
2.1) CD4 CD4 6
> 5 < 50 copies/mL,
CD4 > 500 cells/mm3
CD4
2.2) plasma HIV viral load
6
viral load 6 1
virological failure
CD4
2.3) HIV genotypic drug resistance mutations
4
VL > 1,000 copies/mL genotype
wild type
4
4.4.3
1)
2)
3) (adherence
assessment)
3
212
Management of HIV-Infected Children and Adolescent
213
4.5
4.8
4.8
/ efavirenz, raltegravir, atazanavir
(neuropathy) didanosine, stavudine, zidovudine
zidovudine
zidovudine, protease inhibitors
lopinavir, didanosine
(Hyperbilirubinemia) indinavir atazanavir
nevirapine didanosine
didanosine, stavudine raltegravir
tenofovir atazanavir
(Osteopenia) Protease inhibitors, tenofovir stavudine
Steven Johnson syndrome* nevirapine
nevirapine,efavirenz
(hypersensitivity)* abacavir, nevirapine
(lipohypertrophy) Protease inhibitors, efavirenz
(lipoatrophy) stavudine, zidovudine,didanosine,
Protease inhibitors, stavudine, efavirenz
ritonavir-boosted lopinavir, stavudine, didanosine,
(Glucose intolerance) zidovudine
Lactic acidosis* didanosine, stavudine
zidovudine
PENTA guideline 2015
*
IRIS CD4
viral load
6
2-12
Nontuberculous Mycobacteria,
herpes simplex, Cryptococcus, Mycobacterium tuberculosis
cytomegaloviurs
IRIS 2 paradoxical (worsening) type
unmasking type paradoxical type
unmasking type
IRIS
NSAIDs corticosteroid
214
Management of HIV-Infected Children and Adolescent
215
IRIS 4.1
216
(clinical events)
(1)
CD4 IRIS paradoxical
/ viral load (worsening) (5, 7)
(2) (3)
2560
4.7
( )
HIV RNA < 50 copies/mL
4.7.2
2 NRTIs AZT/3TC TDF/3TC
NNRTIs Efavirenz (EFV) Rilpivirine
(RPV) boosted PI Atazanavir/ritonavir LPV/r
Lopinavir ritonavir
4.7.3
LPV/r
ATV/r
d4T AZT
(lipodystrophy) TDF ABC
218
Management of HIV-Infected Children and Adolescent
219
4.8
(diagnosis of treatment failure in HIV-infected children)
virological failure
plasma HIV Viral load
CD4
virologic failure
CD4
1-2 single dose
NVP
NNRTIs
3 1) virological failure 2) immunological
failure 3) clinical failure
viral load CD4
virological failure immunological failure
clinical failure viral load CD4
CD4
plasma HIV RNA
1. Virological failure 2
1.1
viral load > 200 copies/mL
6
viral load > 50 copies/mL
12
1.2 viral load (viral rebound)
virological failure plasma viral load > 1,000 copies/mL
viral load 50-1,000 copies/mL
viral load
1-3 viral load > 50 copies/mL
virological failure
** NNRTIs plasma HIV viral load > 1000
copies/mL resistance
mutation HIV drug resistance
** boosted PI plasma HIV viral load > 1000
copies/mL resistance mutation 4-6
2. Immunological failure
virological failure CD4
CD4
( 6)
3. Clinical failure
3.1 brain growth,
cognitive function motor function
220
Management of HIV-Infected Children and Adolescent
221
3.2
3.3 AIDS defining condition
4.9
second-line
AZT + 3TC TDF 3TC (FTC)
TDF + 3TC (FTC) AZT 3TC
NVP EFV LPV/r
LPV/r DRV/r
3 NRTIs, NNRTIs, PI
boosted darunavir, etravirine,
raltegravir
4.2
4.2
adherence
CD4 < 200 cells/mm3
1
CD4 plasma HIV VL
adherence
adherence
HIV genotyping VL > 1,000 copies/mL
genotyping
222
Management of HIV-Infected Children and Adolescent
223
224
Management of HIV-Infected Children and Adolescent
225
4.10.1
2NRTIs + 1NNRTIs
2NRTIs + 1NNRTIs (NVP
EFV)
1. 2NRTIs resistance testing
4.9
AZT TDF 3TC
( 3TC )
TDF + AZT AZT TDF K65R
AZT 2 TDF + ABC
ABC TDF
K65R ABC + 3TC
TDF ABC AZT 3TC
ABC + 3TC ABC
2NRTIs AZT + d4T TDF + ddI
d4T + ddI
ddI
()
d4T
lipodystrophy
2. boosted PI
LPV/r boosted PI RTV
ATV/r
ATV > 3
Atazanavir
200 . 300 . 20
Thailand National Guidelines on HIV/AIDS Treatment and Prevention 2017
2560
4.10.2 2NRTIs + PI
2 NRTIs + LPV/r virological
failure
1. 2NRTIs resistance testing
4.10.1 4.9
AZT + 3TC TDF ABC + 3TC
TDF ABC + AZT
ABC + 3TC TDF + AZT
TDF + 3TC (FTC) K65R
AZT + 3TC
TDF + 3TC (FTC) AZT + 3TC
2. 2NRTIs
NNRTIs 2NRTIs
NNRTIs EFV
NVP NRTIs
NNRTIs NRTIs
NRTIs
3TC TAMs TDF ABC
2NRTIs
NNRTIs DRV/r
2NRTIs
226
Management of HIV-Infected Children and Adolescent
227
4.9
(first-line regimen) (second-line regimen)
AZT + 3TC + NVP EFV TDF + 3TC (FTC) + LPV/r1 ATV/r
TDF ABC + 3TC + NVP EFV AZT + 3TC + LPV/r2 ATV/r
AZT + 3TC + LPV/r NNRTIs:
TDF + 3TC (FTC)5 + EFV 3
NNRTIs:
TDF + 3TC (FTC)5 + DRV/r 3
ABC + 3TC + LPV/r NNRTIs:
TDF + AZT+ EFV 4
NNRTIs:
TDF+ AZT + DRV/r
1
TDF + AZT ABC + 3TC TDF + ABC
2
ABC + 3TC ABC
3
TDF ABC + AZT
4
TDF + 3TC (FTC) AZT + 3TC K65R
5
35 tenofovir/
emtricitabine (TDF/FTC) TDF + 3TC
228
Management of HIV-Infected Children and Adolescent
229
Maraviroc (MVC) 16
CCR5 receptor (R5 virus) tropism
50-70
R5 MVC drug interaction
MVC
EFV, ETR PIs
CD4
NNRTIs
NNRTIs ETR
CD4 3TC
mutation CD4
NRTIs CD4
NNRTIs PI NRTIs AZT + 3TC
CD4
4.10.4
1) 1 3
adherence
PIs metabolic 2-3
lipid profile blood sugar 1-2
TDF urinalysis Creatinine 6
CrCl < 50 ./ TDF TDF
2) CD4 3-6
viral load 6 6
viral
4.11
CD4 < 15
,
, -- --
CD4 (immune recovery)
> 25 > 350 cells/mm3 ( > 5 ) 6
CD4 > 15 viral load < 50 copies/mL > 1
lymphoid tissue
(primary
immune response)
memory cell
CD4 (CD4 nadir) < 15
230
Management of HIV-Infected Children and Adolescent
231
(revaccination)
CD4 < 15
CD4 (immune
recovery) > 25 > 350 cells/mm3 ( > 5 ) 6
CD4 > 15 viral load < 50 copies/mL 1
CD4 > 15
4.10
CD4 < 15
1 2 6
HBV vaccine1 HBV1 HBV2 HBV3 3
JE vaccine ( ) 2 JE1 JE2 2
MMR vaccine3 MMR1 1
dT vaccine 7 4 10
1.
1
3 ()
CD4 15
1 antiHBs Ab > 10 mIU/ml
2 anti-HBs Ab
anti-HBs Ab
< 10 mIU/mL 3 (
)
anti-HBs Ab
10-100 mIU/mL 1
CD4
100 mIU/mL
2.
2 1 CD4
6 1
3. -- 1 CD4
6 MMR
4. -- (DTwP, DTaP Tdap) < 7
DTwP DTaP > 7 dT Tdap
4.12
4
1)
2)
3)
4)
232
Management of HIV-Infected Children and Adolescent
233
1)
2)
3)
/
4)
5)
4.13
7
10
www.cqihiv.com
234
Management of HIV-Infected Children and Adolescent
235
4.14
(adherence to antiretroviral treatment in children)
Adherence
Adherence
7
Adherence
Adherence
3 Viral load
4
.
.
.
.
(adherence)
95
adherence
adherence
adherence
4
1 :
2 :
1-2
Cotrimoxazole
(Bactrim) 2-4
3 :
(fixed dose combination)
236
Management of HIV-Infected Children and Adolescent
237
4 :
4.1 ( 7 )
4.2
4.3 :
adherence
(
Visual analog scale )
viral load
4.15
(5Ds)
D1-Disclosure
1)
> 7
2)
3)
4)
D2-Depression self esteem
13
D3-Drug :
D4-Dangers :
( 9-12 )
238
Management of HIV-Infected Children and Adolescent
239
12-14
D5-Daily activity :
(life goals)
www.
cqihiv.com
3
1
1.1
1.2 (Holistic care)
CD4 Viral Load
1.3
1
1-2
1.3.1
1.3.2
240
Management of HIV-Infected Children and Adolescent
241
2
2.1
2.2
3
1
242
Prevention of Mother-to-Child HIV Transmission
243
5
(Prevention of Mother-to-Child HIV Transmission)
1. .. 2558
2. 2
28-32
3.
4.
5. VL 34-36
4
VL
6.
12
VL 50 copies/mL
(standard risk)
VL 50 copies/mL VL
HAART > 12
(high risk)
VL > 50 copies/mL VL
HAART HAART < 12
7.
NNRTIs : AZT + 3TC + LPV/r TDF +
3TC (FTC) + LPV/r
1
HIV VL > 50 copies/mL
HIV VL
AZT + single dose NVP
NNRTI-based HAART
NNRTI
8.
9. 32
raltegravir (400 .)
HAART 32
12 VL > 1,000 copies/mL
32 raltegravir
raltegravir
244
Prevention of Mother-to-Child HIV Transmission
245
< 36
> 72 4 : anti-HIV
( 4th generation) 2
28-32
(Pre-Exposure Prophylaxis PrEP)
36
> 72 4 :
window period (4
)
window period
PrEP
246
Prevention of Mother-to-Child HIV Transmission
247
25-40
.. 2543
.. 2558
0.6 0.8 .. 2551
PCR
3.8
.. 2551 2.0 .. 2557 1.6 .. 2558
PCR
PCR 4.6
.. 2551 2.0 .. 2557 1.9 ..
2558
( 2)
.. 2558
1 .. 2563
.. 2558
1)
19
8 2)
3)
HAART
HAART
12 < 50
copies/mL 1 4)
10
.. 2558 42
0.2
1,500
5.1
Key messages
(dual protection)
CD4 VL
EFV, LPV/r
EE 30
VL < 50 copies/mL CD4 > 350 cells/mm3
248
Prevention of Mother-to-Child HIV Transmission
249
5.1.1
( 5.1)
VL < 50 copies/mL
5.1
1.
2.
3. VL < 50 copies/mL
1.
2.
3. VL < 50 copies/mL
1.
2. VL < 50
copies/mL
3. VL < 50 copies/mL
(3-5 .)
30
14
( 0.5-1
)
LH
LH
24-36
(intrauterine insemination,
IUI)
(ultrasound)
250
Prevention of Mother-to-Child HIV Transmission
251
IUI
> 3-6 (in vitro fertilization,
IVF) (intracytoplasmic sperm
injection)
(sperm washing)
IUI IVF
HIV
HIV (seminal fluid)
3
TDF/FTC 1 24
4
4
5.1.2
WHO (spermicides)
2 Jadelle LNG 2 5
Implanon etonogestrel (ENG) 1 3
252
Prevention of Mother-to-Child HIV Transmission
253
Implanon 24
depot medroxyprogesterone
acetate (DMPA) 150 . 3
DMPA
DMPA
NNRTIs PIs CD4
VL DMPA
ethinyl estradiol (EE) LNG,
norethindrone (NET), norgestimate (NGM)
EE
30-35 EE < 30 (ultra low dose)
5.2
PIs
ATV - EE , NET
ATV/r - EE , NET , NGM
DRV/r EE , NET
LPV/r - EE , NET
RTV - EE , NET
NNRTIs
EFV EE , NGM , LNG
ETR EE , NET
NVP EE , NET
RPV - EE , NET
Integrase inhibitors
RAL - EE
EVG - EE , NGM
30
EE: ethinyl estradiol, NET: norethindrone, LNG: levonorgestrel, NGM: norgestimate
254
Prevention of Mother-to-Child HIV Transmission
255
5.2
Key messages
2
28-32
1.
2.
3.
5.1
5.2
4.
: Hct/CBC, syphilis testing, HBsAg, blood gr, Rh,
anti-HIV, thalassemia screening ultrasound
anti-HIV, syphilis testing (
), thalassemia screening (
thalassemia)
5. (
)
256
Prevention of Mother-to-Child HIV Transmission
257
6.
CD4 6
VL 34-36
4 VL
(anti-HCV) 3
( / )
PMTCT
window
2560
period
5.3.5 CD4
- window period 1 2
- - -
PrEP
- -
- 1 - CD4
28-32
(same day test result)
28
Prevention of Mother-to-Child HIV Transmission
259
5.2
(b) (b)
anti-HIV
5.6
window period 2 5.6
5.7
1
(c)
positive negative
5.2
(a)
(rapid test)
(b)
rapid test
anti-HIV
rapid test
(c)
rapid test
anti HIV,
syphilis screening test HBsAg
5.3
Key messages
: CD4
TDF + 3TC (FTC) + EFV
260
Prevention of Mother-to-Child HIV Transmission
261
NNRTIs
: AZT + 3TC + LPV/r TDF + 3TC (FTC) + LPV/r
HIV genotype RT gene
32
12
VL 32 > 1,000 copies/mL
Raltegravir 400 . 12 . HAART
raltegravir 2-4
: AZT 4
: AZT + 3TC + NVP 6
(
)
CD4
5.3.1
1
5.3
5.3
( CD4 count)
* $:
TDF/FTC + EFV
TDF + 3TC + EFV
# $:
TDF/FTC + LPV/r
TDF + 3TC + LPV/r
AZT + 3TC + LPV/r
* TDF/FTC + EFV TDF + 3TC + EFV
CD4 ( TDF 300 . 24 . + 3TC 300 .
+ EFV 600 . 24 .)
$
32
raltegravir (400 .) - HAART
raltegravir
raltegravir
#
primary drug resistance 8-10
1
-
HIV VL > 50 copies/mL HIV VL
- AZT + single dose NVP NNRTIs-based
HAART NNRTIs
TDF/FTC ( TDF + 3TC)
+ LPV/r AZT + 3TC + LPV/r (TDF 300 . 24 .; AZT 200-300 .
12 .; 3TC 150 . 12 .; AZT + 3TC (300 + 150) 12 .; LPV/r (200/50) 2
12 .) () HIV genotype (RT gene)
( )
NNRTI (NNRTI)
RT genotype
262
Prevention of Mother-to-Child HIV Transmission
263
5.4 HAART
AZT TDF (300 . 24 .)
TDF AZT (300 . 12 .)
LPV/r EFV (600 . 24 .)
EFV LPV/r (200/50) 2 12 .
LPV/r EFV NVP CD4 count < 250 cells/mm3
CD4 > 250 cells/mm3
NVP
LPV, EFV, NVP boosted atazanavir (ATV/r 300/100 . )
EFV, LPV/r, NVP ATV/r HAART
AZT monotherapy AZT
NVP 200 . 1 (SD NVP)
(HAART)
tail regimen
tail regimen*
NVP
* tail regimen: AZT + 3TC TDF/FTC 14
AZT + SD NVP
VL (< 50 copies/mL)
VL 1,000 copies/mL
6
EFV
neural tube defect
Thailand National Guidelines on HIV/AIDS Treatment and Prevention 2017
2560
( 6 )
ultrasound 18-20
12
32
> 1,000 copies/mL
raltegravir (400 .)
- HAART
raltegravir
5.3.2
AZT 300 . 3 . AZT 600 .
AZT
AZT
AZT 600 . 4
AZT VL < 50 copies/mL
3 NVP
NNRTIs
AZT monotherapy NVP 200 .
1
ergot methergine ( oxytocin )
LPV/r EFV severe vasoconstriction
264
5.5
FDA
pregnancy
category*
NRTIs
AZT C CBC
Hb < 8 g/dL Hct
< 24% AZT
TDF
3TC C
3TC
TDF B
Prevention of Mother-to-Child HIV Transmission
NRTIs
TDF
NRTIs
lactic acidosis (
d4T
d4T/ddI
)
FDA
pregnancy
category*
NNRTIs
NVP B ( CD4 > 250
) antihistamine cells/mm3
( chlorpheniramine,
hydroxyzine topical
/ steroid 0.1% TA cream/
) lotion ALT
LPV/r
ALT > 2.5
upper limit
LPV/r
EFV D
Prevention of Mother-to-Child HIV Transmission
EFV
NVP
2-4 EFV neural tube
defect 6
2 .
EFV
ergot methergine
268
FDA
pregnancy
category*
RPV B 20-30
RPV
Pls
2560
2-4
glucose challenge
test ergot methergine
FDA
pregnancy
category*
ATV B indirect ATV
bilirubin ATV/r 300/100 .
TDF
hyperbilirubinemia
ATV
DRV C RTV boosted
800/100 . 12
Integrase inhibitor
Prevention of Mother-to-Child HIV Transmission
RAL C , ,
, , (AST, ALT)
A (
2 3)
B
C
D
X
Prevention of Mother-to-Child HIV Transmission
271
5.3.3
PIs
NNRTIs ()
3
: 3
NNRTIs
NNRTIs NRTIs AZT TDF 3TC (FTC)
14
5.3.4
Key messages
VL 34-36 > 50 copies/
mL VL
HAART < 12
(seroconversion)
AZT 600 .
2 . NVP 200 .
2 NVP
NVP 200 .
(HAART)
(VL > 1000 copies/mL) 38 AZT
NVP 4
PMTCT AZT + 3TC + NVP 6
25-40 5.2
4
AZT 300 . NVP 200 .
AZT 300 . 3 AZT 600 .
2 NVP
NVP
272
Prevention of Mother-to-Child HIV Transmission
273
(standard risk)
VL 50 copies/mL VL HAART
12 AZT 4 ././ 12 .
4 NVP (
5.7)
(high risk)
VL > 50 copies/mL VL HAART
HAART 12
3 AZT 4 ./. 12 .
3TC 2 ./. 12 . NVP 4 ./. 24 . 6
LPV/r < 14
< 14 (expected date of
confinement, EDC)
LPV/r
< 14
PCR 1
NVP LPV/r
AZT 3TC ( 4.6 4)
LPV/r AZT + 3TC + NVP
( 4.6 4) DNA PCR
HIV genotype (viral resistance dried
blood spot )
4
2
DNA PCR
48
> 48
5.7
5.3.5
1. HAART
VL
AZT AZT
wild type AZT
2. NVP
HAART AZT TDF + 3TC (FTC)
+ LPV/r CD4 NVP
3.
3
acute retroviral syndrome (ARS)
3.1
VL < 200 copies/mL
3
274
Prevention of Mother-to-Child HIV Transmission
275
anti-HIV 28-32
6
3.2 (
1 window period
VL 200 copies/mL) ( )
3.2.1)
72
(HIV non-occupational
Post- Exposure Prophylaxis: HIV nPEP) 7
HIV nPEP
( 1-2 ) 72 .
4
AZT TDF + 3TC (FTC) + LPV/r EFV
nPEP
3.2.2) < 36
> 72 4
anti-HIV ( 4th generation)
2
28-32
(Pre-Exposure Prophylaxis PrEP)
TDF/FTC
75
(Partners PrEP) TDF
67 (Partners PrEP)
PrEP
7
3.2.3) 36
> 72 4
window period (4 )
window period
PrEP
PrEP
PrEP
PrEP
5.3
3.2 HIV DNA RNA PCR
276
Prevention of Mother-to-Child HIV Transmission
277
4.
5. anti-HIV inconclusive ()
ARS
2
ARS 3 ()
6. AHI (Acute HIV infection)
HAART
VL < 50 copies/mL
AHI 4-6
AHI 60-90
(ARS) 2-3
10 AHI
AHI
window period
inconclusive AHI
-
(4th generation immunoassay) window period 15-20
278
Prevention of Mother-to-Child HIV Transmission
279
5.3
3
#
1
VL < 200 copies/mL VL VL
anti-HIV 72 3 -1
28-32
6 nPEP* 4 wks
< 36 36
anti HIV
nPEP anti
HIV (4th gen)
(
3rd gen)
2
window period
PrEP**
28-32
()
window period
(4 )
* HIV non-occupational Post-Exposure Prophylaxis
(nPEP) ( 1-2
PrEP**
) 72 .
4
HAART PrEP**
TDF + 3TC + LPV/r EFV
** Pre-Exposure Prophylaxis (PrEP)
TDF/FTC
75
window
(Partners PrEP)
period (4 )
PrEP ( 7)
PrEP**
#
HIV DNA RNA (Qualitative)
TDF/FTC (300/200 .)
+ LPV/r (200/50 .) 2
12 .
2 HAART 4
VL < 50 copies/mL + AZT3 1
EFV 300 . 3 .
600 .
Antepartum Intrapartum Postpartum6 Newborn ( + )
3 (no ANC)
2 . AZT 600 . AZT (syr) 4 ./. 12 . +
3TC (syr) 2 ./. 12 .+
NVP (syr) 4 ./. 24 .
6 5
5.7
2 . AZT 300 . 3 . TDF/FTC/EFV TDF + 3TC + EFV
600 .
+ NVP 200 . 1
(SD NVP)
1. CD4 < 200 cells/mm3 TMP-SMX (80/400 .) 2 24 . double strength TMP-SMX (160/800 .) 1 24 .
2. LPV/r-based HAART 1) HIV VL
> 50 copies/mL HIV VL 2) AZT + single dose NVP NNRTIs-based HAART
Prevention of Mother-to-Child HIV Transmission
NNRTIs
3. AZT VL < 50 copies/mL AZT
4. 32 12 VL
> 1,000 32 Raltegravir 400 . 12 .
5. LPV/r 14 14
6.
- LVP/r-based HAART
5.7
AZT (10 ./.)* 3TC (10 ./.) NVP (10 ./.)
(.) () 4 ./. 2 ./. 12 4 ./.
12 (simplified dosing)
4000-4499 18 . (1.8 . ) 9 . (0.9 . ) 18 . (1.8 . )
3500-3999 16 . (1.6 . ) 8 . (0.8 . ) 16 . (1.6 . )
3000-3499 14 . (1.4 . ) 7 . (0.7 . ) 14 . (1.4 . )
2500-2999 12 . (1.2 . ) 6 . (0.6 . ) 12 . (1.2 . )
2000-2499 10 . (1.0 . ) 5 . (0.5 . ) 10 . (1.0 . )
1500-1999 8 . (0.8 . ) 4 . (0.4 . ) 8 . (0.8 . )
* 30-35 : AZT 2 ./. 12
8 2
* < 30 : AZT 2 ./. 12
8 4
5.4
282
Prevention of Mother-to-Child HIV Transmission
283
HAART
5.8
HAART
CD4 count 6
Viral load - 34-36 *
4
CBC AZT 4-8
Hb < 8 g/dL Hct < 24% Hb < 8 g/dL Hct < 24%
AZT TDF AZT TDF
Creatinine TDF 3 6
creatinine clearance
< 60 mL/min TDF creatinine clearance
< 50 mL/min TDF
AZT
ALT
2.5 upper 6
limit NVP 2.5 upper
limit NVP
EFV LPV/r
Urine sugar
urine sugar
LPV/r
EFV
TDF UA 6
urine protein
50 g GCT LPV/r LPV/r
24-28 LPV/r
blood sugar 4
140 mg/dL 100 g OGTT blood sugar 140 mg/dL
100 g OGTT
* HAART 8-12
VL < 1,000 copies/mL VL 34-36
4 VL
1,000 copies/mL VL > 50 copies/mL
3 AZT/3TC/NVP 6
50 g GCT (glucose challenge test) glucose 50
50% glucose 100 . blood glucose glucose 1
100 g OGTT (oral glucose tolerance test)
8 fasting blood glucose glucose
100 blood glucose 1, 2 3 glucose
OGTT
1) glucose 1
OGTT 4
2) glucose 2
284
Prevention of Mother-to-Child HIV Transmission
285
5.5
5.5.1
(artificial rupture of membranes)
oxytocin
4
scalp electrode forceps extraction vacuum
extraction / (episiotomy)
5.5.2
1. 38 VL 34-36
1,000 copies/mL
2.
4 VL
Thailand National Guidelines on HIV/AIDS Treatment and Prevention 2017
2560
3.
4.
> 3,500
4
(oligohydramnios)
scalp electrode, forceps extraction, vacuum extraction
prolonged rupture of membranes
286
Prevention of Mother-to-Child HIV Transmission
287
5.6
hypothermia
5.6
vitamin K BCG HBV
5.7
5.7.1
1)
4-6 pap smear
( 1 )
CD4 6
Thailand National Guidelines on HIV/AIDS Treatment and Prevention 2017
2560
2)
3)
3.1)
3.2)
2
4)
5)
5.1
288
Prevention of Mother-to-Child HIV Transmission
289
5.7.2
5.6 5.7
18
AZT (CBC)
7-10 g/L 21-30%
2
< 7 g/L < 21%
AZT 20-30
1 AZT
AZT
4.8
TMP-SMX prophylaxis ( TMP 150 mg/m2/day SMX 750 mg/m2/day)
3 4-6
PCR > 6
1
CD4 < 15%
5.8
(Early infant diagnosis EID)
DNA PCR
( 2 4)
5.10
*
(standard risk) HIV DNA PCR 2 1
2-4
50 copies/mL
VL AZT 4
(HAART) >12
(high risk) HIV DNA PCR 4 * 1,
> 50 2 4
copies/mL 3 (AZT + 3TC +
VL NVP) 6
12 1
3
NVP
LPV/r ( 4)
* HIV PCR
(DBS) (
)
anti-HIV 18
( 2 4)
1 HIV DNA
PCR 2
290
Prevention of Mother-to-Child HIV Transmission
291
6
(Opportunistic Infections: Prophylaxis and Treatment)
6.1 (Tuberculosis)
6
2 9
12
Directly Observed Treatment
CD4
CD4 < 50 cells/mm3 2 4
CD4 50 cells/mm3
2 4
2 8
rifampicin efavirenz
efavirenz nevirapine raltegravir dolutegravir
protease inhibitor
rifampicin
Isoniazid Preventive Therapy
CD4 < 200 cells/mm3
rifampicin
paradoxical reaction immune reconstitution inflammatory
syndrome (IRIS)
294
Opportunistic Infections: Prophylaxis and Treatment
295
(
.. 2556)
AFB
AFB
2
acid fast bacilli (AFB)
nontuberculous mycobacteria
(NTM)
needle aspiration
tissue biopsy
pancytopenia bone marrow aspiration
(cerebrospinal fluid)
> 14
AFB
NTM
polymerase chain reaction (PCR) real-time PCR
(molecular NTM
method)
3
(primary infec-
tion)
(Tuberculin
skin test TST)
indetermine
interferon gamma
release assay
(IGRA)
296
Opportunistic Infections: Prophylaxis and Treatment
297
()
TST IGRA
IGRA
6
6.1-6.2
6.1
6
9
2
12
2 4 isoniazid, rifampicin,
ethambutol pyrazinamide
4-7 isoniazid rifampicin
2 4-7
6.2
Isoniazid* 5-8 ./. (300 .)
Rifampicin (R) 10 ./. (450-600 .)
Ethambutol (E) 15-20 ./. (800-1,200 .)
Pyrazinamide (Z) 20-25 ./. (1,000-2,000 .)
* pyridoxine 25-50 . isoniazid
6-9
.. 2557
(http://www.pidst.net/A367.html)
2 (intensive phase) 4 isoniazid, rifampicin, pyrazi-
namide ethambutol
4-7 (continuation phase) isoniazid rifampicin isoniazid
rifampicin pyrazinamide
ethambutol
isoniazid rifampicin
miliary 10
12
prednisolone 1-2 ./ 4-6
miliary
endobronchial TB
6.3
Isoniazid 10-15 ./. ( 300 .)
Rifampicin 10-20 ./. ( 600 .)
Pyrazinamide 30-40 ./. ( 2,000 .)
Ethambutol 15-20 ./. ( 1,200 .)
3-4 2 (bactericidal)
Amikacin 15-20 ./. ( 1,000 .)
Kanamicin 15-30 ./. ( 1,000 .)
Ethionamide 15-20 ./. ( 1,000 .) 2-3
Capreomycin 15-30 ./. ( 1,000 .)
Cycloserine 10-20 ./. ( 1,000 .) 2
Levofloxacin (Lfx) < 5 20 ././ 2
5 10 ././ ( 1 )
Moxifloxacin (Mfx) 7.5-10 ././ ( 400 .)
Ofloxacin (Ofx) 15-20 ././ ( 800 .)
streptomycin, kanamycin, amikacin
ethionamide quinolones, cycloserine PAS
(
.. 2556)
(intensive phase)
2 2
isoniazid rifampicin
DOT
300
Opportunistic Infections: Prophylaxis and Treatment
301
(
.. 2556)
isoniazid rifampicin ethambutol
pyrazinamide 3-5
isoniazid, rifampicin pyrazinamide
alkaline phosphatase bilirubin
transaminase enzyme rifampicin
AST ALT > 5 > 3
isoniazid, rifampicin pyrazinamide ethambutol,
quinolones, streptomycin
AST ALT < 2 total bilirubin
< 1.5 isoniazid,
rifampicin pyrazinamide
1
ALT > 3
2 2SIRE/7IR, 9IRE, 9RZE
1 2SIE/16IE, 24-18IE +
quiniolone
ethambutol metabolites pyrazinamide
creatinine clearance < 30 /
3
streptomycin
hemodialysis
Rifampicin
CYP450 efflux multi-drug transporter P-
glycoprotein non-nucleoside reverse transcriptase
inhibitors (NNRTIs) protease inhibitors
NNRTIs efavirenz nevirapine
protease inhibitor
1. protease inhibitor NNRTIs ( efavirenz
nevirapine) integrase inhibitor ( raltegravir)
302
Opportunistic Infections: Prophylaxis and Treatment
303
CD4
6.4
6.4
CD4
< 50 cells/mm3 2 4
50 cells/mm3 * 2
4
2
8
*
2
rifampicin
rifampicin
1. Efavirenz 600 ./
2. Nevirapine 200 . 2 lead-in
3. Raltegravir 400 . 2
4. Dolutegravir (DTG) 50 . 2
Thailand National Guidelines on HIV/AIDS Treatment and Prevention 2017
2560
2-8
IRIS CD4
CD4
6
6 6.5
6.5
6
CD4
CD4 < 15% 2
CD4 15% * 2
2-8
*
2
6.6
rifampicin
NNRTIs efavirenz
efavirenz nevirapine (Lead-in) Integrase
inhibitor raltegravir dolutegravir
NNRTIs
rifampicin quinolones
PIs CD4 < 15% aminoglycoside
PIs
rifampicin 2
CD4 15% maintenance
304
Opportunistic Infections: Prophylaxis and Treatment
305
rifampicin quinolone
IZ IE +
quinolone 10-16
PIs
rifampicin 2 (
rifampicin )
NRTIs 3 zidovudine (AZT)
stavudine (d4T) + lamivudine (3TC) + abacavir (ABC)
rifampicin
NNRTIs PIs
NNRTIs PIs VL 100,000
copies/mL
TB paradoxical IRIS
2
12
radiculomyelitis
(serositis)
3
2-4
IRIS
IRIS
306
Opportunistic Infections: Prophylaxis and Treatment
307
TB paradoxical IRIS (non-steroidal
drugs systemic corticosteroids)
IRIS
prednisolone 1 ././ 2
4-8
Unmasking TB IRIS
(latent TB infection)
10
10
isoniazid 9
5 .
isoniazid
6-9
isoniazid preventive therapy (IPT) TLTI (treatment latent
tuberculous infection)
Thailand National Guidelines on HIV/AIDS Treatment and Prevention 2017
2560
tuberculin
48-72
(anergic)
randomized controlled trials
meta-analysis IPT
IPT
IPT
6.7 IPT
(TST) INH
(induration < 5 )
TST (induration 5 ) INH
IPT
1
308
Opportunistic Infections: Prophylaxis and Treatment
309
IPT 9
IPT
:
(LTBI)
IPT active hepatitis (acute or chronic)
symptoms of peripheral neuropathy
INH
6.8
Isoniazid 300 . 9
pyridoxine 25-50 .
Isonazid 10 ./. ( 300 .)
9
2
(pyrazinamide + rifampicin)
Rifampicin 10 ./. ( 600 .)
isoniazid 4
IPT
6 2
6.1
(treatment latent tuberculous infection isoniazid preventive therapy)
TST
(induration 5 .) (induration < 5 .)
IPT 9 IPT
CD4
310
Opportunistic Infections: Prophylaxis and Treatment
311
1. (unexplained)*
2. 1
3. 5 1
4. > 3 1
2
* 2
1. ( 2 )
2. 1
3. ( 6.2)
4.
1
(LTBI)
isoniazid 9
6.2
4
1 4
- 1
- ( 2 )
- *
-
IPT *** **
* (
3 z-score) ( 2 z-score)
(> 5)
(Strong recommendations, low quality of evidence)
** ,
contact investigation
*** INH preventive therapy (IPT)
312
Opportunistic Infections: Prophylaxis and Treatment
313
6.2
(primary and
secondary prophylaxis)
PCP
Pneumocystis jirovecii
PCP 3-6
1 CD4
P. jirovecii
30-65
A. Primary prophylaxis
CD4 < 200 cells/mm3 CD4 < 14
oropharyngeal candidiasis AIDS-defining illness ()
PCP PCP 4-6
CD4 PCP
12
CD4 CD4 15% CD4 500 cells/mm3
1-5 CD4 < 200 cells/mm3 6
CD4 clinical CDC category C
314
Opportunistic Infections: Prophylaxis and Treatment
315
co-trimoxazole (TMP-SMX) single-
strength (SS) (TMP 80 .-SMX 400 .) 1-2
2 toxoplasmosis
TMP 5 ./. 150 ././ SMX 750
././ ( TMP 320 . SMX 1,600 .) 1-2
3
co-trimoxazole
1 dapsone 2 ./. ( 100 .)
4 ./. ( 200 .) ( dapsone
atovaquone 1-3 2
30 ./. 4-24 45 ./.
12 1,500 . )
clindamycin primaquine
PCP
CD4 > 200 cells/mm3 3
primary prophylaxis CD4 < 200 cells/mm3
primary prophylaxis
6 CD4 3
1-5 CD4 > 15% > 500 cells/
mm3 6 CD4 15% > 200 cells/mm3
1 1 CD4
316
Opportunistic Infections: Prophylaxis and Treatment
317
1)
PCP
co-trimoxazole kernicterus
bilirubin
2)
PCP
co-trimoxazole co-trimoxazole
50
co-trimoxazole 5-7 pentamidine
isethionate 4 ././ 60-90
dapsone 2 ././ atovaquone 30-40 ././
2 21 co-trimoxazole
rapid desensitization desensitization
C. Secondary prophylaxis
PCP
primary prophylaxis
CD4 > 200 cells/mm3 3
CD4 < 200 cells/mm3
PCP CD4 > 200 cells/mm3 secondary
prophylaxis CD4
primary prophylaxis
1
PCP PCP CD4
6.2.2 Cryptococcosis
CD4 > 100 cells/mm3 3
B. Treatment
Induction phase: 2
Amphotericin B 0.7-1.0 ././ fluconazole
800 ./
(meningitis)
Amphotericin B 1.0 ././
fluconazole
Fluconazole 1,200 ./
amphotericin B
Consolidation phase: 8-10
Fluconazole 400-800 ./
Itraconazole 400 . 2
cryptococcal antigen
(cryptococcal anti-
genemia) consolidation phase
1)
fluconazole itraconazole teratogenic effect
2 amphotericin
B
2)
amphotericin B 0.7-1.0 ./.
14 fluconazole 12 ./. 6-12 ./
./ 8
fluconazole 12 ./.
6-12 ./. ( 600 .)
fluconazole 5-6 ./. 8
C. Secondary prophylaxis
cryptococcosis induction
consolidation secondary prophylaxis
fluconazole 200-400 ./
fluconazole 6 ./. ( 200 .)
itraconazole 200 ./
itraconazole 5 ./. ( 200 .)
cryptococcosis
cryptococcosis 1
320
Opportunistic Infections: Prophylaxis and Treatment
321
6.2.3 Candidiasis
Candidiasis mucocutaneouscandidiasis
oropharyngeal candidiasis, cervicovaginal candidiasis, esophageal candidiasis
diaper dermatitis invasive candidiasis
oropharyngeal candidiasis CD4 < 100
cells/mm3, VL , WBC < 500 cells/mm3 esophageal candidiasis
herpes simplex virus CMV
A. Primary prophylaxis
B. Treatment
1. Oropharyngeal candidiasis
Clotrimazole oral troches 10 . 4-5 7-14
Fluconazole 100 . 7-14
Nystatin oral solution 500,000 5
7-14
322
Opportunistic Infections: Prophylaxis and Treatment
323
324
Opportunistic Infections: Prophylaxis and Treatment
325
2)
Congenital toxoplasmosis pyrimethamine 2 ././ 2
1 ././ 2-6 1 ./. 3
sulfadiazine 50 ./. 2 folinic acid 12
toxoplasmosis
acquired CNS ocular systemic toxoplasmosis pyrimethamine
2 /./ 3 1 ././ folinic acid 10-25 ./
sulfadiazine 25-50 ./. 4 6
sulfadiazine clindamycin 5-7.5 ./. 4 (
600 ./ ) pyrimethamine folinic acid dexamethasone
( > 1,000 ./)
pyrimethamine CBC
C. Secondary prophylaxis
toxoplasma
pyrimethamine 25-50 ./ sulfadiazine 500-1,000
. 4 folinic acid 10-25 ./
sulfadiazine 85-120 ././ 2-4
pyrimethamine 1 ./. 15 ./. ( 25 .)
folinic acid 5 . 3
326
Opportunistic Infections: Prophylaxis and Treatment
327
pyrimethamine 25-50 ./ clindamycin 600 .
8 . folinic acid 10-25 ./ co-trimoxazole SS 2
clindamycin 20-30 ././ 4
pyrimethamine 1 ./. folinic acid 5 . 3
CD4 > 200 cells/mm3 6 CD4
< 200 cells/mm3
6 CD4 > 200 cells/mm3 > 15%
1-5 CD4 15% ( CD4 > 500 cells/mm3)
3 6
1
Penicilliosis histoplasmosis
CD4 < 100 ( penicilliosis) 150 ( histoplasmosis) cells/mm3
penicilliosis papulonecrotic
skin lesions histoplasmosis
Wright stain
histoplasmosis penicilliosis
65 penicilliosis
A. Primary prophylaxis
penicilliosis histoplasmosis
cryptococcosis
cryptococcosis
primary prophylaxis 2
(optional)
CD4 < 100 cells/mm3 ( penicilliosis) 150 cells/mm3
( histoplasmosis)
itraconazole 200 .
itraconazole 5 ./.
itraconazole histoplasmosis penicilliosis
fluconazole cryptococcosis
CD4 > 100 cells/mm3 ( penicilliosis)
150 cells/mm3 ( histoplasmosis) 6
CD4
B. Treatment
Induction phase
Amphotericin B 0.6-0.7 ././ 7-14
328
Opportunistic Infections: Prophylaxis and Treatment
329
Itraconazole 200 . 3 3 200 .
2 14
Consolidation phase
Itraconazole 200 . 2 10-12
Amphotericin B 0.4-0.5 ././ 10-12
Fluconazole 800 .
1)
itraconazole
itraconazole teratogenic effect amphotericin
B
2)
2.1) Histoplasmosis itraconazole 6-8 ././ 3-12
amphotericin B 1 ./. 4-6
itraconazole 5 ./.
2.2) Penicilliosis amphotericin B 0.7 ./. 2
itraconazole 10 ././ 2 10
amphotericin B
2
C. Secondary prophylaxis
penicilliosis histoplasmosis
Itraconazole 200 . itraconazole 5 ./.
Fluconazole 400 .
Amphotericin B 0.6-0.7 ./.
malabsorption
CD4 > 100 cells/mm3 ( penicilliosis) 150
cells/mm3 (histoplasmosis) 6
CD4
6 CD4 > 100 cells/mm3
( penicilliosis) >150 cells/mm3 ( histoplasmosis)
1-5 CD4 15% itraconazole
1 6
330
Opportunistic Infections: Prophylaxis and Treatment
331
CMV CD4
50 cells/mm3
CMV
1
(congenital infection)
congenital CMV
microcephaly, intracranial calcification, bone marrow
suppression
CMV retinitis
CD4 50 cells/mm3
fundus
screening CMV retinitis 4-6
5
CD4 5% CD4 < 50 cells/mm3
6 floater
CMV IRIS
A. Primary prophylaxis
CD4
100 cells/mm3
B. Treatment
Ganciclovir 5 ./. 12 . 2-3
3-6
Valganciclovir 900 . 2 2-3
Ganciclovir intravitreous 2,000 / 1
Ganciclovir implant 4.5 .
vitreous 6-8
ganciclovir retinitis
CMV
CD4
CMV
CMV
ganciclovir
CD4 VL
1)
332
Opportunistic Infections: Prophylaxis and Treatment
333
2)
CMV CMV retinitis ganciclovir
5 ./. 12 . 2-3 congenital CMV
infection ganciclovir 6 secondary
prophylaxis
C. Secondary prophylaxis
CMV retinitis
Valganciclovir 900 .
Ganciclovir 5 ./.
Ganciclovir intravitreous 2,000 1 2-4
( )
retinitis
CMV retinitis 3-6
CD4 > 100 cells/mm3 3-6
CD4 < 100 cells/mm3
6 CD4 > 100 cells/mm3 1-5
CD4 15% CD4 500 cells/mm3 6
6
3-6
334
Opportunistic Infections: Prophylaxis and Treatment
335
clarithromycin 500 . 2 azithromycin
1,000-1,250 .
clarithromycin 7.5 ./. 2 azithromycin
20 ./. ( 1,250 .) 5 ./. (
250 .)
CD4 > 100 cells/mm3
3 CD4 < 50 cells/
mm3
6 CD4 > 100 cells/mm3 2-5 CD4
200 cells/mm3 3
Treatment
Clarithromycin 500 . 2 ethambutol 15 ././
Azithromycin 500 . ethambutol 15 ././
( 4-8
) quinolones
(ciprofloxacin 500-750 . 2 levofloxacin 500 .
moxifloxacin 400 . ) amikacin 15 ./.
1)
clarithromycin
azithromycin
2)
clarithromycin 7.5-15 ./. ( 500 .)
336
6.9
Secondary prophylaxis
Tuberculosis 2 HRZE/4-7IR
Isoniazid 5-8 ./. (300 .)
Rifampicin 10 ./. (450-600 .)
Ethambutol 15-20 ./.
(800-1,200 .)
Pyrazinamide 20-25 ./.
(1,000-2,000 .)
Pyraidoxine 20-30 ./.
(1,000-2,000 .)
Pneumocystis Co-trimoxazole TMP 15-20 Clindamycin 600 . Co-trimoxazole Dapsone 100 .
Opportunistic Infections: Prophylaxis and Treatment
Consolidation phase
Fluconazole 400-800 ./ Itraconazole 400 ./ 8-10
8-10
Toxoplasmosis
2560
2-3 / 1 . .
Valganciclovir 900 . 2
2-3 Ganciclovir implant 6-8 Ganciclovir intravitreous
2,000
1 2-4
levofloxacin 500 .
moxifloxacin 400 .
Amikacin 15 ./.
Opportunistic Infections: Prophylaxis and Treatment
341
3 6
> 6 : CD4 100 cells/mm > 6 : CD4 100 cells/mm3
3
3 6
MAC
1
CMV Not applicable < 1 :
1-5 : CD4 500 cells/mm3 15%
6
6 : CD4 > 100 cells/mm3 6
342
HIV Prevention
343
7
(HIV Prevention)
(comprehensive HIV prevention package)
PrEP 7.2-7.5
PrEP
PEP
TDF + 3TC TDF/FTC
RPV 25 .
ATV/r 300/100 .
LPV/r 400/100 . 12 . 800/200 .
DRV/r 800/100 .
TDF + 3TC TDF/FTC
RAL 400 . 12 .
DTG 50 .
EFV 600 .
(source)
oPEP nPEP
6
0, 1 3 anti-HCV 3
delayed HIV seroconversion
7.3
7.1
(Antiretroviral-based HIV prevention)
2
CD4
344
HIV Prevention
345
(Strategic Timing of AntiRetroviral Treatment : START)
CD4 > 500 cells/mm3
CD4 500 cells/mm3
.. 2558 CD4
.. 2557
TasP
50 250,000
20
CD4 50 CD4 < 100 cells/mm3
(
)
TasP
TasP
346
HIV Prevention
347
PrEP
2) PROUD
FTC/TDF 1 PrEP
PrEP 86
PrEP
2 PrEP
7.1 PrEP
adherence
Adherence
PrEP
adherence
IPERGAY MSM TDF/FTC 86% - -
PROUD MSM TDF/FTC 86% - -
Partners PrEP Serodiscordant TDF/FTC 75% 81% 90%
heterosexual couples TDF 67% 86%
TDF2 Heterosexual men TDF/FTC 63% 79% 78%
and women
iPrEX MSM TDF/FTC 44% 51% 92%
Bangkok TDF People who inject TDF 49% 84% 74%
drugs
FEM-PrEP Women TDF/FTC 6% 35-38% No protection
VOICE Women TDF/FTC -4% < 30% No protection
TDF -49% No protection
PrEP
PrEP
PrEP
600-2,000
PrEP
( 7.2)
7.2 PrEP
PrEP
PrEP
Post-Exposure Prophylaxis (PEP)
3
6
PrEP 18
/
adherence
PrEP
348
HIV Prevention
349
PrEP:
Urine PrEP
pregnancy test (
PrEP) PrEP
1 4
PrEP
1
PrEP PrEP
/
(fibrosis)
PrEP
PrEP
PrEP
2
APRI score = [AST (IU/L)/upper limit of normal (IU/L)]/platelet(109/L) x 100
3
> 40 > 50
alpha-fetoprotein (AFP)
6-12 .. 2559
350
HIV Prevention
351
7.4 PrEP
TDF/FTC 300/200 . 1
PrEP
3
PrEP
7
PrEP
Methadone Maintenance Treatment (MMT)
PrEP
PrEP PrEP
PrEP 4
( window period)
PrEP
PrEP
(active)
PrEP
PrEP
PrEP ()
PrEP
PrEP
2 PrEP
PrEP
TDF
(
1 200 1%)
1 3 6 9 12 PrEP
3
Creatinine creatinine
CrCl
6
(HBsAg)
HBsAg-negative
STI
6
( )
1 10
3-4
352
HIV Prevention
353
PrEP PrEP
Cr 1 200
PrEP
*
(acute HIV infection)
acute HIV infection anti-HIV
PrEP
nucleic acid
testing HIV RNA
PrEP (
PrEP )
controversy
PrEP
PrEP
( PrEP )
Seroconversion PrEP
HIV
non-occupational PEP (nPEP)
7.1.3.1
(HIV occupational Post-Exposure Prophylaxis: HIV oPEP)
(occupational exposures)
(percutaneous injury)
(contact of mucous membrane)
(contact of non-intact skin)
(dermatitis)
354
HIV Prevention
355
0.3 ( 95
0.2-0.5) 0.09 ( 95
0.006-0.5) 0.09
HIV oPEP 7.1
HIV oPEP 7.6 HIV oPEP
( 1-2 ) 72
* 4
HIV oPEP
(source)
VL
()
VL detectable VL NNRTI-
based regimen TDF/FTC TDF + 3TC + boosted PI
source PI-based regimen NNRTI resistance
TDF/FTC TDF + 3TC + RAL DRV/r
Dolutegravir ( 7.7)
undetectable VL
7.7
* 72
HIV oPEP
HIV oPEP
7.6
(Standard precautions)
72
1 3
6
delayed HIV seroconversion
/
HIV
oPEP CBC, Cr SGPT
/
356
HIV Prevention
357
7.1
0.9% NSS
0.9% NSS
70%
alcohol betadine
solution
5% Chlorhexidine gluconate
anti-HIV
24 . source anti-HIV
source
358
HIV Prevention
359
*
3
**
7.1.3.2
(HIV non-occupational Post-Exposure Prophylaxis: HIV nPEP)
/
7.8
Thailand National Guidelines on HIV/AIDS Treatment and Prevention 2017
2560
7.8
10,000
63
23
138
8
11
4
*
*
8-12
cervical ectopy
360
HIV Prevention
361
10,000
*
*
- HIV nPEP 7.9
- HIV nPEP HIV nPEP
7.10 HIV oPEP
HIV nPEP
( 1-2 ) 72 *
4 HIV oPEP
- HIV nPEP
HIV oPEP 7.7
- HIV nPEP
1-3 HIV nPEP
1 PrEP
- HIV nPEP
72 anti-HIV
1 3
/
HIV nPEP CBC, Cr SGPT
/
* 72
HIV nPEP
Thailand National Guidelines on HIV/AIDS Treatment and Prevention 2017
2560
362
HIV Prevention
363
.. 2539
Randomized controlled
trials 3
3
.. 2548-2550
51-60 .. 2550
58 6
(Herd
immunity)
1) (Langerhans
cells), CD4+, macrophage
364
HIV Prevention
365
2)
(keratin)
(micro injuries)
3)
4)
(keratinization)
(glans)
9.1
(balanitis)
(posthitis) HSV-2
(HR 0.72; 95% CI, 0.56-0.92) high-risk human papillomavirus (HPV) (RR 0.65;
95% CI, 0.46-0.90 RR 0.67; 95% CI, 0.51-0.89)
HPV (RR, 1.39; 95% CI, 1.17-1.64)
(chancroid)
HPV
(phimosis)
1 3
3
Shang Ring
2
Shang
Ring
366
HIV Prevention
367
7.11
(
)
1
/
"risk compensation"
1
American Academy of Pediatrics
.. 2555
American College
of Obstetricians and Gynecologists
7.12
risk compensation
368
HIV Prevention
369
7.3
2-5
3-11
(cost effectiveness strategy)
2556-2558 /
5.35 15.1
5.33 2
50-70 70-80 85-90
Test and Treat
.. 2555
Urine PCR
(polymerase chain reaction) Chlamydia trachomatis (CT)
6.6 Neisseria gonorrhoeae (NG) 2.9 CT
NG 11.4 16.1
(venue-base female sex worker)
NG CT .. 2553, 2555
2557 ( 7.2)
()
( )
( .. 2558)
25 HIV GC. CT
20.0
20
17.7
15
11.1
10 9.2
7.27
5 4.9 4.2
3.38 2.7 2.4 2.7
2.17 1.9 2.4 1.6
1.07 0.98 1.1
0
2553 2555 2557
370
HIV Prevention
371
1.
()
2.
()
(
download a idssti.ddc,moph,go.th
17
(STIQUAL program)
3,405
41.0
1
15.4
NAT
anti-HIV
7.3
372
7.3
3 1 ; ;
; RPR/VDRL titer visit
/ /
RPR/VDRL titer 4 RPR/VDRL titer 4
3
RPR/VDRL
Anti-HIV(1) 3 1
6 2
HIV Prevention
,
HIV positive HIV negative
Benzathine penicillin G
2.4
Neurosyphilis 3
anti-HIV
2560
7.4
.. 2531
(ISO) .. 2533
3 49 52 54
0.05-0.08
( 87)
HSV-2 ( 92)
chlamydia ( 26) gonorrhea
( 62) trichomonas
HPV
HPV
98 88
15
(polyurethane)
7
5.5
(polyurethane)
(latex)
374
HIV Prevention
375
15-24 8.8
80
2.3 89.2
21.5
33 0.8
78.8
aidsstithai.org/female
7.5
.. 2558
1.9-2.2
80 (The Thai
working group) .. 2558
7,324 11
.. 2532 2557
19
(Harm reduction)
7.13
1. (Outreach programme)
2.
376
HIV Prevention
377
3.
4.
5.
6.
7.
8.
9.
10.
8
(Service delivery guidance)
Treatment cascade
NAP plus Treatment
cascade
viral load
1 viral load < 50 copies/mL
8.1
-
-
/ . .. 2558
Service delivery guidance
381
4
NAP plus website
.
HIV
1. ()
(STI)
( PWID)
2. ()
3. ()
/ (
PWID)
(Reach)
1.
4
1.1 (STI)
(PWID)
1.2
PWID
1.3
1.4 Unique Identifying Code (UIC)
(Recruit)
1.
(pre-test counseling)
(mobile clinic)
382
Service delivery guidance
383
Reach Recruit
Recruit Reach
1. Outreach worker
2.
(Peer)
()
Drop in center (Mobile clinic)
1. ( MSM TG MSW FSW PWID Migrant
)
2.
3.
2 (Mobile clinic)
1. Mobile clinic
2. HCT SDR
(Mobile clinic)
3. Mobile
clinic
HCT SDR
drop-in center
Mobile clinic
384
Service delivery guidance
385
1.
drop-in center ..
2.
drop-in center ..
..
Telemedicine Skype
4
1.
2.
( outreach worker website /
)
Path2Health
www.adamslove.org
5
1.
386
Service delivery guidance
387
2.
3 8.2
8.2
6
1.
2.
3. ()
HCT SDR
4. UIC (Unique
Identifying Code)
/
8.3
1.
2.
388
Service delivery guidance
389
3.
4.
5.
8.3
390
Service delivery guidance
391
1.
2.
3.
4.
5.
/
6. /
8.2 (Test)
1. HCT
()
(
)
2.
3.
4.
5. ()
392
Service delivery guidance
393
1
(Same day result HIV testing; SDR)
1. ( .. Drop-in center)
2.
( .. Drop-in center)
3. Mobile clinic
.. Mobile clinic
(Community based HIV testing)
(Concentrated
epidemic)
CD4 Drop-in center (DIC)
99
(HIV Opt out testing) HCT
(Normalize HIV testing)
2) (Community-based HCT)
HCT
(KAP)
HCT
CD4
394
Service delivery guidance
395
2
(1)
(2)
1.
2.
3.
4.
1.
2. -
-
3.
(
)
4.
5.
(
)
1.
2.
3. CD4
4.
2
1.
2.
2
1)
396
Service delivery guidance
397
2) -
8.1
6
3 (Friendly service)
1.
2.
5
1. 1
2
2. 3
4
3. 5
6
hotline,
website, facebook
7
4. 8
398
Service delivery guidance
399
5. 9
1.
8.1
6
4.
8.3 (Treat)
1.
2. 3
3. CD4 (
CD4 < 200 cells/mm3)
1 (Friendly service)
1.
2.
8.2 3
2
1.
2.
400
Service delivery guidance
401
(Holistic care)
9
35
1.
1.1
1.2 CD4 /
1.3 CD4
1.4 (HIV Viral load)
1.5 HIV Genotype
2.
2.1
2.2 PCP (Pneumocystis jiroveci
pneumonia)
2.3
2.4
2.5 CMV retinitis CD4 < 100 cells/mm3
2.6
2.7
2.8 Pap Smear
VIA 1
3.
3.1
3.2
3.3 (HAART)
3.4
402
Service delivery guidance
403
3.5
(Adherence)
3.6
4.
4.1
4.2 (Voluntary Counseling and
Testing)
(Provider-Initiated HIV Testing and Counseling, PITC)
4.3
5.
5.1
6.
6.1 (Prevention with Positives, PwP)
6.2
(PMTCT)
6.3
(PMTCT)
6.4
6.5
7.
7.1
7.2
7.3 /
8.
8.1
9. ()
9.1
9.2
9.3
HIVQUAL 10
3 1) 2) /
3)
http://www.cqihiv.com/
(.)
1. ..
2554
404
Service delivery guidance
405
1. CD4 3
2. viral load 1
3.
HIV resistance testing 4
2
NAP
1. CD4
2.
3.
3 4
NAP
8.4 (Retain)
()
1.
(
)
2.
3. viral load < 50 copies/mL
4.
1 (Retention in care)
1.
2. 12
406
Service delivery guidance
407
8.4
8.4
Re-Engagement
in Care
Loss to Follow up
Retention in Care
5
1) (Individual/Intrapersonal factors)
(Predisposing)
(Enabling)
(Perceived need)
2) (Relationship/Interpersonal factors)
3)
4) (Community factors)
5) (Policy and healthcare factors)
1. 2. 3. 5.
(Intrapersonal factors) (Interpersonal factors) (Community factors) (Policy and
healthcare factors)
1.1
/
1.2
4.
1.3
(Audit)
RRTTR
408
Service delivery guidance
409
1)
Adherence
2)
Treatment Literacy
3)
4)
5) (Case manager
Retention specialist)
Case management
Case manager
6)
3-5
31 18
2 Adherence
1.
2. 100%
410
Service delivery guidance
411
Adherence 100%
Adherence
Adherence
Treatment
Literacy
Adherence stigma discrimination
CD4 < 200 cells/mm3
1
(fast track)
*
VL > 50 copies/mL
(VL < 50 copies/mL)
1 ()
3-6
*
> 1 VL < 50 copies/mL
1.
(HIV/AIDS Treatment Literacy)
Treatment Literacy
(Treatment Literacy or TL)
7
1.
2.
3.
4.
5.
6.
7.
7
7
(Key message)
adherence
412
Service delivery guidance
413
Treatment Literacy
1.
TL
(Key message)
2.
3.
1.
2.
3.
4.
5.
414
8.1
./.
on site
(mobile HCT) (coaching on-site)
./.
.
Service delivery guidance
()
././.
routine lab
./.
(coaching on-site)
()
CD4 ( point of care CD4 .),
./.
1. 1. / 1
./. VL suppression ( 50 copies/mL)
2.
3. HCT 2.
Service delivery guidance
417
4
(Drug resistance monitoring & prevention)
1. 12
90 5
2. viral load 12
< 50 copies/mL 85
3. 12 viral load < 50
copies/mL 90
4.
5. drug resistance
2
(1)
(2)
(Early Warning
Indicators) (3)
8.2
(4) (5)
Lost follow-up
Poor adherence adherence
* case management /
. 8.6
Service delivery guidance
419
(Visit adherence drug adherence)
viral load
HIV resistance testing
1.
2. World Health Organization global strategy for the surveillance and
monitoring of HIV drug resistance: an update. World Health Organization 2012,
ISBN 978 92 4 150476 8.
1.
Thailand National Guidelines on HIV/AIDS Treatment and Prevention 2017
2560
CD4
420
Service delivery guidance
421
1. (Real life) /
International
HIV/AIDS Alliance (AIDS Net)
2. (Life-Skills Activities Manual
on HIV and AIDS)
1.
(
)
(PrEP- Pre-exposure Prophylaxis)
7
PEP (Post-exposure Prophylaxis)
8.5
1.
1.
2.
/
2573
2 1)
2)
1)
2)
/
422
Service delivery guidance
423
1.
2. 75
3x4 ( 8.5) 4
1)
2)
3) 4)
3
1.
1.1
1.2
2.
2.1
2.2 Consultative meeting
2.3 ( 2-3 )
2.4
(
)
2.5
/
3.
3.1
424
Service delivery guidance
425
Consultative
meeting /
Case conference
S&D
(50% ) +
/ /
2560
Case conference
/
E-learning
/
3 4
1. 3.
1. 2. / 3. 2. ( 2 2-3) 4.
1. Laura Nyblade, Anne Stangl, Ellen Weiss and Kim Ashburn. Combating HIV stigma in health care settings: what works?. Journal
of the International AIDS Society 2009, 12:15 doi:10.1186/1758-2652-12-15.
2. UNAIDS. 2014. Reduction of HIV-related Stigma and Discrimination.
Service delivery guidance
427
2
/
1.
( 8.6)
1.
2.
/
Thailand National Guidelines on HIV/AIDS Treatment and Prevention 2017
2560
3.
1)
2)
3)
Standard
Precaution
4.
5.
/
428
Service delivery guidance
429
8.6
1.
2.
3.
/
4.
PDCA
...
1.
2.
3.
(
)
1. .
. :
, 2555. http://
www.thailandaids.org/main/index.php/2014-02-17-04-23-20
8.6
1.
1.
2.
2
8.3 R-R-T-T-R
430
Service delivery guidance
431
8.3
Surveillance
( )
Program data
() Surveillance
- REACH & RECRUIT
() () Program data
1. STI Surveillance
2.
3. STI /
( PWID)
- TEST
1. Program data
Surveillance
2.
3.
4.
5. ()
- TREAT
1. Program data
2. 3
3. CD4 (
CD4 200)
- RETAIN
1. Program data
Estimation
2. 12
3.
4.
5. viral load < 50
copies/mL
3
(Effective Continuous
Quality Improvement)
(
)
8.7
432
Service delivery guidance
433
8.7
Death
( ) ARV resistance
( )
-
Process, Outcomes, Impact
1.
( )
2.
3. .. 2558-2562
Abacavir (ABC)
Emtricitabine (FTC)
Lamivudine (3TC)
Tenofovir (TDf)
Zidovudine (AZT) X X
HIV entry/integrase inhibitor
Dolutegravir (DTG)
Nevirapine (NVP) X X X
2560
Potease inhibitor
Lopinavir X X X
Ritonavir X X X
: 2016 X
(Dose and Route of HIV medication in Adults)
2
() /
Nucleoside reverse transcriptase inhibitors (NRTIs)
Abacavir 300 . 12 . alcohol 1.5 ./ Hypersensitivity reaction (HSR) HLA-B*5701
(ABC) 300 . dehydrogenase 1226 . positive
Appendix
600 .
glucuronyl transferase HLA ABC
82%
HSR
ABC
200 .
2560
( Insulin resistance/
.
2 . )
Tenofovir 300 . 17 ./ , Fanconi syndrome, proximal tubulopathy
disoproxil 300 . > 60 . osteomalacia
fumarate TDF
(TDF) 3 HBV-coinfected
() /
Zidovudine 300 . 12 . GAZT 1.1 ./ macrocytic anemia
(ZDV) 100, 250 300 200 . 12 . GAZT 7 . neutropenia
.
Lactic acidosis/severe hepatomegaly with hepatic
steatosis ()
Appendix
Hyperlipidemia
Insulin resistance/
Lipoatrophy
Myopathy
Lamivudine 150 . 12 . 57 ./
(3TC) 150 300 . 300 . 1822 . HBV-coinfected 3TC
70%
Complera:
FTC 200 . + RPV 25
. + TDF 300 .
Truvada Teno-EM:
FTC 200 . + TDF 300
.
() /
Non-nucleoside reverse transcriptase inhibitors (NNRTIs)
Efavirenz 600 . 40-55 .
(EFV) 50 (europsychiatric symptoms)
200 . CYPs 2B6 3A4 Increased transaminase levels
600 CYP3A4
.
EFV with 1 ( cannabinoid benzodiazepine
TDF + FTC EFV 600 . + )
Teratogenic in non-human primates and potentially
Appendix
50%
2560
lead-in
7
lead-in
28
() /
Rilpivirine 25 . 25 . CYP3A4 substrate 50 .
(RPV) EFV
1
RPV + TDF RPV 25 . +
+ FTC TDF 300 . +
FTC 200 .
Protease inhibitors (PIs)
Atazanavir ATV 300 . + RTV 100 CYP3A4 inhibitor 7 . Indirect hyperbilirubinemia
(ATV) 200 300 . . substrate PR interval prolongation: first degree
Appendix
2560
50 .
Elvitegravir 1 EVG: CYP3A, ~13 .
(EVG) UGT1A1/3
EVG 150 . + CrCl < 70 cobi: CYP3A, CYP2D6
cobi 150 . + mL/min (minor) bone mineral density
cobi/TDF/ TDF 300 . +
FTC FTC 200 . HBV-coinfected FTC
TDF
(,
CDC Classification 2014
1.
CD4
CD4 lymphocytes
1
2
3 2
3
CD4
< 12 1-5 6-12
CD4 CD4 CD4
3 %CD4 3 %CD4 %CD4
(cell/mm ) (cell/mm ) (cell/mm3)
1 : 1,500 34 1,000 30 500 26
2 : 750-1,499 26-33 500-999 22-29 200-499 14-25
3 : < 750 < 26 < 500 < 22 < 200 < 14
450
Appendix
451
(WHO Classification System for HIV-Infected Children)
452
Appendix
453
10. cryptococcosis
11. (disseminated endemic mycosis) histoplasmosis
coccidiomycosis, Penicillosis ()
12. Cryptosporidium
Isospora
13. HIV encephalopathy
14. progressive multifocal leukoencephalopathy
15. HIV-associated cardiomyopathy
16. HIV-associated nephropathy
17. Kaposis sarcoma
18. lymphoma Z (B-cell non Hodgkin lymphoma)
4-< 9 . 12 ./. 12 . (
9-30 . 9 ./. 12 . )
30 . 300 . 12 . d4T
AZT
(- 6 )
35 4 ./. 12 .
30-< 35 2 ./. 12 .
2 3 ./. 12 .
< 30 2 ./. 12 . 4
3 ./. 12 .
Lamivudine (3TC) : 10 mg/mL < 4 2 ./. 12 .
( 60 mL) 4 4 ./. 12 .
: 150, 300 . ( 150 mg/dose) ( 30 )
3 VL < 40 copies/
mL 8-10
./. ( 300 .)
CrCl < 50 mL/min
Appendix
25-< 60 . 250 . 24 .
2560
60 . 400 . 24 .
Abacavir (ABC) : 20 mg/mL 8 ./. 12 . ( 300 mg/dose)
: 300 . 3
14-< 20 . 150 . 12 . 300 . 6
20-< 25 . 150 . , 300 . HLA-B* 5701
450 .
25 . 300 . 12 . 600 .
Tenofovir (TDF) : 300 . 2-< 12 8 ./. ddI
2 12 35 . 300 .
Lopinavir Atazanavir
14-< 20 .: 150 . Tenofovir
20-< 30 .: 225 . CrCl < 50 mL/
> 30 .: 300 . min
48 . CrCl 30-49 mL/
min 72-96 . CrCl 10-29
mL/min
Appendix
Nonnucleoside reverse transcriptase inhibitor (NNRTI)
Nevirapine (NVP) : 10 mg/mL < 1 6 ./. 12 . Rifampicin NVP
: 200 . ( Lead-in) 20-30% NVP
1 < 8 200 mg/m2 12 . 2-4
8 120-150 mg/m2 12 .
( 200 mg/dose)
(Lead-in) 14
24 .
12 .
) 32.5-< 40 . 400 .
40 . 600 .
400 .
< 40 .
Etravirine (ETR) : 100 . 16-< 20 . 100 . 12 .
6 20-< 25 . 125 . 12 . 1-2
25-< 30 . 150 . 12 .
30 . 200 . 12 . NNRTI ETR
Rilpivirine 25 . >12 > 12 25 .
VL < 100,000 copies/mL
VL < 50
copies/mL
Fixed dose combined pill of NRTI and NNRTI
AZT + 3TC : AZT 300 . + 30 . 1 12 .
(fixed dose 3TC 150 .
combination) 30-60 .
Appendix
AZT 200 mg/dose
GPO-VIR S30 d4T 30 . + 3TC 150 GPO-VIR S30 2-4
. + NVP 200 . NVP 160-200
mg/m2 12 .
(Lead-in) NVP
14 10-< 14 . 12 .
GPO-VIR d4T+ 3TC 14-25 . 12 .
14 1
GPO-VIR > 25 . 1 12 .
40 . 300 . 2
> 12 25
. film-coated tablet 400 . 1
2
Dolutegravir 50 . 12 50 .
Efavirenz Rifampicin 50
> 40 . . 2
Elvitegravir : 85, 150 . 12
> 35 ATV/r LPV/r 85
. .
DRV/r 150 .
< 42
2560
1-2
EFV 2-4 4 mcg/mL
absence
2) Mitochondrial dysfunction
Lactic acidosis 1-20 metabolic serum lactate
NRTIs acidosis routine serum IV fluid fluoride-oxalate
d4T, ddI (anion gap >16) lactate tube
serum lactate 4
> 5 mmol/L
NRTIs
TDF ABC
AZT 3TC
Pancreatitis serum ddI
Appendix
http://
2560
(BMI) www.rihes.cmu.ac.th/Ped_
HIV/10-BMI-WHR_z_score/
index.html
lipoatrophy
/ d4T
AZT ABC
TDF
NRTIs
d4T ddI AZT
4) metabolic syndrome insulin resistance ( type 2 diabetes impaired fasting glucose 100 mg/dL
impaired glucose tolerance test) 2 130/85 mmHg BMI
(triglycerides 150 mg/dL HDL cholesterol < 40 mg/dL) albuminuria metabolic syndrome
atherosclerosis
Hyperglycemia, FBS
insulinresistance, fasting blood 6
diabetes sugar > 126
mg/dL 3 60
NRTIs random BS
Appendix
d4T NNRTIs ()
2560
14-18 40 .
Fibrate
8-10 10 .
LDL > 190 mg/dL LDL 4
>160 mg/dL atorvastatin
> 6 10-20 .
statin
5)
liver enzyme ALT / AST /
(hepatotoxicity) () AST ALT NVP
ARV NVP
6 ALT
NVP AST > 5-10 fluconazole
NNRTIs NVP 10 upper normal limit
(NVP EFV) upper normal hepatitis A, B, C EBV
hypersensitivity limit 2-4 CMV
Appendix
NRTIs ALT
lactic acidosis AST 5-10
upper normal limit
6 lactic
acidosis
AZT, d4T, ddI
Indirect bilirubin
hyperbilirubinemia liver
ATV enzyme indirect
bilirubin
2560
6)
Hb <7-8 g/dL AZT
AZT
MAC, TB
CBC 6
AZT
AZT d4T
heart failure CBC TDF
3
6
6
CBC: absolute CBC 6
neutrophil AZT
(neutropenia) count < 500 CBC MAC
AZT cells/mm3 3
absolute neutrophil (severe < 250 6
(< 250 cells/mm3) cells/mm3) 6
7) Allergic reaction/ Hypersensitivity
Appendix
maculo-papular
rash 2-4 2-8 antihistamine ABC hypersensitivity
2-3
(rechallenge)
systemic hypersensitivity
NVP ABC TMP- systemic
SMX,
systemic ()
1-2 NVP
2560
NNRTIs systemic
NVP TMP-SMX, EFV
AZT, NVP
ddI, LPV/r, ATV 2
8)
Impaired renal function U/A, Cr. eGFR
eGFR < 60 mL/min/1.73 m2 6 Cr. Schwartz
Fanconi syndrome eGFR (
TDF , acute tubular aminoacid, )
IDV necrosis, interstitial nephritis, glucose uric
renal proximal renal tubulopathy, serum glucose TDF FEP = [(Urine
cortical atrophy nephrogenic DI, Cr. acidosis, phosphate/serum
acute renal , sodium potassium phosphate)/(urine
failure phosphate phosphate wasting creatinine/plasma
Appendix
x-ray absorptiometry)
(bone
mineral density)
12
Appendix
475
creatinine clearance
4-12
1.
1)
8 4
8-10 1
2)
3)
4)
5)
6)
2.
476
Appendix
477
5-10 2-3
5
2
8 1:2 ( 1 2 )
4-5 1:1 ( 1 1 )
3.
1)
2) 1-2 2-3
3-4 4
4-6 6-7 5
6 7-8 4
3)
4)
5) 2
6)
4.
1)
2)
3)
4)
5) 2-3
6)
2
2 1 2
ORS
478
Appendix
479
5.
(month) (g) (mL/dose) (dose/day) (mL/day) (kg/month)
0 3,000 75 6 450 2
1 3,400 85 6 510 2.3
2 4,200 105 6 630 2.8
3 5,000 125 6 750 3.5
4 5,800 145 6 870 4
5 6,600 160 6 960 4.3
6 7,400 185 6 1,110 5
7 7,800 195 5 975 4.5
8 8,200 205 5 1,025 4.6
9 8,600 215 5 1,075 4.8
10 9,000 225 4 900 4
11 9,400 240 4 960 4.3
12 9,800 240 4 960 4.3
: ()
.. ;
1 = 30 mL; 1 4.5 g; 50 kg/
6.
450 1
450 () 1 ()
(
)
()
1.
2.
3.
4.
5.
6.
KY-jelly
7.
480
Appendix
481
1.
2.
3.
4.
5.
1.
(: )
2.
3.
4.
5.
482
Appendix
483
6.
7.
8.
rapid desensitization TMP-SMX
484
Reference
485
486
Reference
487
1. .
2557. 1. :
; 2557.
2. .
.. 2550-2554
[]. [ 17 2556]. : http://bps.ops.
moph.go.th/E-book/statistic/statistic54/2.1.5_54.pdf
3.
.
.. 2546-2549. . 2550.
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.
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.
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6. . Test and Treat MSM/TG
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