Thai Guideline on HIV Diagnosis and Treatment

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ISBN 978-974-297-984-3

1 255320,000

79465_001-016_M4.indd 2 13/11/2553 19:25

.. 2553

National Guidelines on HIV/AIDS Diagnosis and Treatment:

Thailand 2010

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NationalGuidelinesonHIV/AIDSDiagnosisandTreatment:Thailand2010

79465_001-016_M4.indd 3 12/11/2553 10:24

.

Mrs.MichalleMcConnell

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16

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1 (Introduction) 43

2 49

(HIV Laboratory for Diagnastic and Monitoring)

49

2.1 50

2.2 55

2.2.1 55

2.2.2 antibody 57

2.3 68

2.3.1 CD4 68

(CD4 cell counts)

2.3.2 70

(viral load)

2.3.3 72

(HIV drug resistance testing)

17

National Guidelines on HIV/AIDS Diagnosis and Treatment: Thailand 2010

79465_017-042_M4.indd 17 12/11/2553 10:35

2.4 75

79

3 81

(Management of HIV-Infected Adult)

3.1 81

3.2 94

(acute HIV infection)

3.3 96

(nave)

3.3.1 96

3.3.2 100

3.3.3 103

3.3.4 d4T phase out plan 104

3.4 106

3.5 (drug interaction) 112

18

.. 2553

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3.6 116

3.7 121

(Immune Reconstitution Inflammatory Syndrome: IRIS)

3.8 130

3.9 133

(adherence to antiretroviral therapy)

3.9.1 adherence 133

3.9.2 adherence 134

3.10 142

(diagnosis and management of treatment failure)

3.10.1 142

3.10.2 144

3.11 149

3.12 166

3.12.1 166

19


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3.12.2 168

3.12.3 170

3.12.4 172

3.12.5 174

methadone

3.12.6 176

3.13 178

3.14 181

3.15 185

(post-exposure prophylaxis)

3.15.1 185

(HIV Occupational Post-Exposure

Prophylaxis: HIV OCC-PEP)

3.15.2 186

(HIV Sexual Post-exposure

Prophylaxis: HIV SEX-PEP)

20

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198

4 211

(Management of HIV-Infected Children)

211

4.1 212

4.1.1 212

4.1.2 212

4.1.3 224

4.2 228

(ARV therapy in nave HIV-infected children)

4.2.1 228

4.2.2 230

4.2.3 233

(antiretroviral nave)

21


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4.2.4 234

NVP

12

4.2.5 235

(antiretroviral therapy in children with

opportunistic infection)

4.3 240

4.4 242

4.5 252

(Immune Reconstitution Inflammatory

Syndrome: IRIS)

4.6 257

(diagnosis of treatment failure in HIV-infected

children)

4.6.1 258

4.6.2 261

22

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4.7 262

4.7.1 263

genotyping

4.7.2 genotyping PIs 266

4.7.3 267

2NRTIs + 1NNRTI

4.7.4 3 275

NRTIs, NNRTIs PIs

4.7.5 275

NRTIs 2 (dual NRTIs therapy)

4.7.6 276

dual NRTIs

4.7.7 277

4.8 278

4.9 280

4.9.1 280

23


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4.9.2 280

4.10 281

(adherence to antiretroviral treatment in children)

4.11 283

285

5 293

(Prophylaxis of Mother to Child

Transmission: PMTCT)

293

5.1 295

5.2 299

5.2.1 300

5.2.2 302

5.2.3 303

5.2.4 304

(no ANC)

24

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5.3 315

5.4 316

HAART

5.5 319

5.5.1 319

5.5.2 319

(elective caesarean section)

5.6 320

5.7 321

324

6 329

(Opportunistic Infection: Prophylaxis and Treatment)

6.1 Candidiasis 330

6.2 Cryptococcosis 334

6.3 Cytomegalovirus (CMV) infection 338

25


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6.4 Mycobacterium avium complex (MAC) infection 342

6.5 Penicilliosis histoplasmosis 347

6.6 Pneumocystis pneumonia (PCP) 351

6.7 Toxoplasmic encephalitis 357

6.8 Tuberculosis 362

373

26

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379

Schematic representation of the UNAIDS and 381

WHO HIV testing strategies

382

(AIDS-defining 383

illnesses CDC classification)

Child-Pugh Score 384

(drug interaction) 385

rapid desensitization 409

TMP-SMX

411

418

421

Creatinine Clearance 432

433

434

27


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2[1] 76

2[2] 77

2[3] 78

3[1] 95

acute retroviral syndrome

3[2] 98

3[3] 101

3[4a] NRTIs 107

3[4b] NNRTIs 109

3[4c] PIs INSTIs 110

28

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3[5] 121

3[6] IRIS 125

3[7] 132

3[8a] adherence 137

/

3[8b] adherence 139

/

3[9] 2 147

3[10] 150

3[11] 169

3[12] 171

3[13] PIs 175

methadone

3[14] 179

3[15] 184

29


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3[16a] HIV OCC-PEP 189

3[16b] HIV OCC-PEP 190

3[16c] HIV OCC-PEP 191

HIV SEX-PEP

3[17] 192

HIV OCC-PEP

3[18] 192

3[19a] HIV SEX-PEP 194

anti-HIV

3[19b] HIV SEX-PEP 195

30

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3[19c] HIV SEX-PEP 196

3[20] 197

HIV SEX-PEP

4[1a] 215

2553

4[1b] Hib 217

4[1c] PCV 217

4[2a] 1-6 221

4[2b] 7-18 221

4[3] 232

4[4] 242

31


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4[5] IRIS 257

4[6a] genotyping NRTIs 265

4[6b] genotyping NNRTIs 266

4[7a] NRTIs 270

4[7b] PIs 271

4[8] 279

%CD4

5[5] 318

GCT OGTT

6[1] CD4 primary 371

secondary prophylaxis

6

6[2] CD4 primary 372

secondary prophylaxis

1-

[7] PIs 405

[8] 406

NNRTIs, RAL, PIs

[9] rapid desensitization 410

TMP-SMX

[10] 416

CD4

[11] (staging) 417

[12] 421

[13] 433

34

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2[1] 59

18

2[2] 65

18

2[3] 74

(HIV-1 drug resistance)

3[1] 188

3[2] 193

4[1] IRIS 254

4[2] 261

4[3] 262

4[4] 274

35


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5[1] 297

5[2] 298

[1] Schematic representation of the UNAIDS 381

and WHO HIV testing strategies

36

.. 2553

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ABC Abacavir

ATV Atazanavir

AZT Zidovudine

Clar Clarithromycin

CCBs Calcium channel blockers

ddI Didanosine

d4T Stavudine

ddC Zalcitabine

DRV Darunavir

EC Enteric coated

EE Ethinyl estradiol

EFV Efavirenz

ETR Etravirine

FTC Emtricitabine

GCV Ganciclovir

HAART High active antiretroviral therapy

IDV Indinavir

INH Isoniazid

IVIG Intravenous immune globulin

LPV/r Lopinavir/ritonavir

37


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NNRTI Non-nucleoside reverse transcriptase inhibitor

NRTI Nucleoside reverse transcriptase inhibitor

NVP Nevirapine

PAS Para-aminosalicylic acid

PI Protease inhibitor

PPIs Proton pump inhibitors

PZA Pyrazinamide

/r Ritonavir boosted

RAL Raltegravir

RBT Rifabutin

RTV Ritonavir

SQV Saquinavir

TDF Tenofovir

TMP Trimethoprim

TMP-SMX Trimethoprim/sulfamethoxazole

TPV Tipranavir

3TC Lamivudine

38

.. 2553

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BCG Bacillus Calmette-Gurin

DTP Diphtherias, tetanus, pertussis vaccine

DT/dT Diphtheria, tetanus vaccine

DTaP/Tdap Diphtherias, tetanus, acellular pertussis vaccine

DTwP Diphtheria, tetanus, whole cell pertussis vaccine

HAV Hepatitis A vaccine

HbOC Polyribose ribital phosphate-outer membrane protein complex

HBV Hepatitis B vaccine

Hib Haemophilus influenza type B vaccine

HPV Human papilloma vaccine

IPV Injection polio vaccine

JE Japanese encephalitis vaccine

MMR Measles, mumps, rubella vaccine

OPV Oral polio vaccine

PCV Pneumococcal conjugate vaccine

PRP-OMP Haemophilus B conjugate vaccine

PRP-T Polyribose ribital phosphate-tetanus toxoid

PS23 23-valent polysaccharide vaccine

39


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AFB Acid-fast bacilli

AUC Area under the curve

BMI Body mass index

CMV Cytomegalovirus

CO2 Serum bicarbonate

CSF Cerebrospinal fluid

CXR Chest x-ray

EKG Electrocardiography

FBS Fasting blood sugar

GCT Glucose challenge test

GDM Gestational diabetes mellitus

HAART Highly active antiretroviral therapy

HAV Hepatitis A virus

HBV Hepatitis B virus

HCV Hepatitis C virus

Hct Hematocrit

HPV Human papilloma virus

INR International normalised ratio

IRIS Immune reconstitution inflammatory syndrome

KS Kaposi sarcoma

LDL Low-density lipoprotein

MAC Mycobacterium avium complex

40

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MDR-TB Multi drug resistant TB

OFC Occipito frantal circumference

OGTT Oral glucose tolerance test

OI Opportunistic infection

PCP Pneumocystic pneumonia

PML Progressive multifocol leukoencephalopathy

PMTCT Prevention of mother to child transmission

RBC Red blood cell

RPR Rapid plasma reagin

TAMs Thymidine analog mutations

TB Tuberculosis

TC Total cholesterol

TG Triglyceride

VCT Voluntary counseling and testing

VDRL Venereal disease research laboratory test

VLDL Very low-density lipoprotein

WBC White blood cell

WHO World Health Organization

XDR-TB Extensively drug resistant TB

.

.

41


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42

.. 2553

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1

.. 2527

10

(Introduction)

1

43


1

79465_043-048_M4.indd 43 13/11/2553 19:28

()

.. 2535

.. 2543-2544

3,000

.. 2543-2544

2 1)

2)

.. 2545

3

Three by Five

(3x5) (WHO)

3 2005

(The Global Fund to Fight AIDS, Tuberculosis and Malaria)

44

.. 2553

1

79465_043-048_M4.indd 44 13/11/2553 19:28

1

50,000

.. 2545 .. 2547

Vender Managed Inventory

(VMI)

.. 2549

.. 2553

4 1)

2)

3)

4)

WHO

45


1

79465_043-048_M4.indd 45 13/11/2553 19:28

Hospital Accreditation (HA),

HIV Quality Thailand (HIVQUAL-T)

2

(HIV laboratory for diagnosis and monitoring)

(Provider-Initiated Counseling and Testing: PICT)

18

antibody

CD4 viral load

46

.. 2553

1

79465_043-048_M4.indd 46 13/11/2553 19:28

3

(management of HIV-infected adults)

methadone

4

(management of HIV-infected children)

47


1

79465_043-048_M4.indd 47 13/11/2553 19:28

5

(prevention of mother-to-child transmission)

3

HAART

Glucose Challenge Test (GCT)

6

(opportunistic infections: prophylaxis and treatment)

CD4 primary secondary prophylaxis

48

.. 2553

1

79465_043-048_M4.indd 48 13/11/2553 19:28

(HIV Laboratory for Diagnostic and Monitoring)

CD4

viral load

2

49


2

79465_049-080_M4.indd 49 13/11/2553 19:30

2.1

(Voluntary

Counseling and Testing: VCT)

(pre-test / post-test counseling)

(group counseling)

(individual counseling)

50

.. 2553

2

79465_049-080_M4.indd 50 13/11/2553 19:30

(Provider-Initiated Testing and Counseling: PITC)

(opt-out technique)

51


2

79465_049-080_M4.indd 51 13/11/2553 19:30

52

.. 2553

2

79465_049-080_M4.indd 52 13/11/2553 19:30

1)

2)

- - -

3)

4)

5)

6)

7)

8)

9)

10)

53


2

79465_049-080_M4.indd 53 13/11/2553 19:30

1)

2

2)

3 (window period)

/ 3

antibody (seroconversion)

3)

1

54

.. 2553

2

79465_049-080_M4.indd 54 13/11/2553 19:30

2.2

2

antibody

2.2.1

1)

p24 Ag

(core)

p24 Ag

p24 Ag

p24 Ag

antibody 5

5

antibody antibody

(indeterminate)

2) (Nucleic acid

AmplificationTest:NAT)

RNA

(qualitative RNA)*

* (positive or negative)

55


2

79465_049-080_M4.indd 55 13/11/2553 19:30

proviral DNA

antibody

p24 Ag

antibody

18 antibody

(positive)

(negative)

-

-

-

antibody antibody

56

.. 2553

2

79465_049-080_M4.indd 56 13/11/2553 19:30

2.2.2 antibody

antibody

35 .. 2550

99.5

99.0

antibody

1) (ELISA)

HIV antigen solid phase

antigen antibody

substrate

2) (agglutination)

HIV antigen

(simple test)

3) dotlineimmunoassay

HIV antigen solid phase

(dot) (line)

(rapid test)

57


2

79465_049-080_M4.indd 57 13/11/2553 19:30

18

antibody

3

(WHO)

Western blot 2[1]

ELISA, simple test rapid test

58

.. 2553

2

79465_049-080_M4.indd 58 13/11/2553 19:30

2[1]

18

( 5)

(1)

3 (A3)

(Non Reactive) (A1-)

(1)

1 (A1)

(1)

2 (A2)

A1

A2 (A1+, A2-)

A1 A2

A1 A2

(A1-, A2-)

A1

A2

(A1+, A2-)

A1 A2

(A1+, A2+)

(Anti-HIV Positive)(2)

2

A1, A2

A3

(A1+, A2+, A3-)

A1, A2 A3

(A1+, A2+, A3+)

(Anti-HIV Negative)

(3)

(Indeterminate)

(Reactive) (A1+)

A1 A2 (A1+ A2+)

59


2

79465_049-080_M4.indd 59 13/11/2553 19:30

(1) A1, A2 A3 1, 2 3 antibody

antibody antigen

1 2 3 (2)

(newly diagnosed) 2 antibody

1 (3) (indeterminate) 2

/ 3 6 A1, A2 A3

6

(indeterminate)

antigen antibody

(HIV Ag/Ab) fourth generation

p24 Ag

HIV Ag/Ab

p24 Ag / antibody

antibody anti-HIV 2

p24 Ag

anti-HIV p24 Ag blocking

anti-p24 antibody

HIV Ag/Ab

18

(false positive)

60

.. 2553

2

79465_049-080_M4.indd 60 13/11/2553 19:30

antibody

3 (A1, A2 A3)

antigen

antigen

A1

(sensitivity) 3 *

A2 A3

(specificity)

simple test

rapid test

* Ag/Ab windows period

61


2

79465_049-080_M4.indd 61 13/11/2553 19:30

2[1]

1. (anti-HIV negative) antibody

2. (anti-HIV positive) antibody

3

3. (indeterminate)

antibody

2 / 3 6

(indeterminate)

62

.. 2553

2

79465_049-080_M4.indd 62 13/11/2553 19:30

18

antibody

antibody

12

antibody 95

antibody 12

antibody 18

2[2]

proviral DNA PCR

(dried blood spot)

2-3

1

EDTA 2-3 mL

48

63


2

79465_049-080_M4.indd 63 13/11/2553 19:30

1:32

CSF RPR neurosyphilis

85


3

79465_081-148_M4.indd 85 13/11/2553 19:31

-

2

neurosyphilis

3.1.3

1)

latent infection primary tuberculosis

10

(life time risk) 50

5-10

6

86

.. 2553

3

79465_081-148_M4.indd 86 13/11/2553 19:31

CXR

2) CMVretinitis

CMV

CD4

100 cells/mm3

(sensitivity 7)

indirect ophthalmoscope 1

CD4 100 cells/mm3

87


3

79465_081-148_M4.indd 87 13/11/2553 19:31

3)

)17

$%

QBQ TNFBS

4)

)17

$%

QBQTNFBS

88

3

79465_081-148_M4.indd 88 13/11/2553 19:31

anal pap smear

6 1

3.1.4

1)

89


3

79465_081-148_M4.indd 89 13/11/2553 19:31

1.1)

17-30

(11-58 )

90

.. 2553

3

79465_081-148_M4.indd 90 13/11/2553 19:31

-

-

-

-

1.2)

/

91


3

79465_081-148_M4.indd 91 13/11/2553 19:31

-

-

-

3.14

2)

BMI (kg/m2)

17

BMI 18.5 2

92

.. 2553

3

79465_081-148_M4.indd 92 13/11/2553 19:31

PIs

-

-

- 6

93


3

79465_081-148_M4.indd 93 13/11/2553 19:31

3.2 (acuteHIVinfection)

4090

acute retroviral syndrome 3[1]

infectious

mononucleosis streptococcus syphilis

viral load

( 100,000 copies/mL)

anti-HIV

negative indeterminate qualitative HIV-RNA p24 Ag

viral

set point

94

.. 2553

3

79465_081-148_M4.indd 94 13/11/2553 19:31

3[1] acute retroviral syndrome

96

74

70

(erythematous maculopapular rash)

70

54

32

32

27

14

13

(thrush) 12

( aseptic meningitis,

peripheral neuropathy, facial palsy,

Guillain-Barr Syndrome, brachial neuritis

cognitive impairment) 12

95


3

79465_081-148_M4.indd 95 13/11/2553 19:31

3.3 (nave)

3.3.1

1)

CD4 viral load

2)

CD4

..2549/2550 3[2]

3) viral load

CD4

(AIDS-related

illness)

CBC, CD4,

viral load (), FBS, AST, ALT, lipid

profile (TC, TG, LDL), HBsAg, anti-HCV, VDRL, urine

analysis, CXR, pap smear

TDF IDV

96

.. 2553

3

79465_081-148_M4.indd 96 13/11/2553 19:31

serum creatinine creatinine

clearance ABC

HLA-B*5701

hypersensitivity

fundoscopy (eye ground)

CD4 100 cells/mm3

CMV retinitis

IRIS

97


3

79465_081-148_M4.indd 97 13/11/2553 19:31

CD4

(cells/mm3)

(AIDS-defining illness)*

**

350

>350

CD4 6

CD4 >350 cells/mm3

3[2]

* (AIDS-defining illness)

**

(Pruritic Papular Eruptions: PPE)

14 10 3

herpes zoster 2 dermatomes

98

.. 2553

3

79465_081-148_M4.indd 98 13/11/2553 19:31

CD4350cells/mm3(specialconsiderationforART

initiation)

1) HBV HCV

HBV HCV

3.12.4

2) 50 (CD4

>350-500 cells/mm3)

3) discordant couples, HIV-associated

nephropathy

99


3

79465_081-148_M4.indd 99 13/11/2553 19:31

3.3.2

5

1) Nucleoside or nucleotide reverse transcriptase inhibitors

(NRTIs or NtRTI) zidovudine (AZT), stavudine (d4T), lamivudine (3TC),

emtricitabine (FTC), didanosine (ddI), abacavir (ABC), tenofovir (TDF)

fixed-dose combination AZT/3TC 300/150 mg,

d4T/3TC 30/150 mg, TDF/FTC 300/200 mg (FTC fixed-dose

combination TDF )

2) Non-nucleoside reverse transcriptase inhibitors (NNRTIs)

nevirapine (NVP), efavirenz (EFV), etravirine (ETR) NVP

fixed-dose combination NRTIs d4T/3TC/NVP 30/150/

200 mg AZT/3TC/NVP 250/150/200 mg

3) Protease inhibitors (PIs) indinavir (IDV), ritonavir

(RTV), nelfinavir (NFV), saquinavir (SQV), lopinavir/ritonavir (LPV/r),

atazanavir (ATV), darunavir (DRV)

4) Integrase inhibitors (INSTIs) raltegravir (RAL)

5) Fusion inhibitors (FIs) enfuvirtide (ENF)

NNRTIs-based regimen NNRTIs

PIs-based regimen

.. 2549/2550

3[3]

100

.. 2553

3

79465_081-148_M4.indd 100 13/11/2553 19:31

NRTIs

+

NNRTIs

NNRTIs

PIs

Preferred

EFV(6)

NVP(7)

Preferred

AZT + 3TC(1)

TDF + 3TC/FTC(2)

LPV/r(8)

Alternative Alternative

ABC + 3TC(3)

d4T + 3TC(4)

ddI + 3TC(5)

ATV/r

DRV/r(9)

SQV/r

3[3]

101


3

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3[3]

(1) AZT + 3TC NRTIs (2) TDF NtRTIs

creatinine clearance

HBV TDF + 3TC/FTC (3) ABC + 3TC NRTIs

AZT, d4T, ddI TDF ABC

hypersensitivity reaction NVP ABC

NVP(4) d4T + 3TC NRTIs d4T

AZT, TDF 6-12

d4T (5) ddI + 3TC AZT, d4T TDF

(6) EFV NNRTI

NVP EFV

(7) NVP NNRTI

AZT + 3TC

CD4 250 cells/mm3

(8) LPV/r PI

nave 800/200 mg 24 . 400/100 mg 12 .(9) DRV/r nave 800/100 mg 24 .

IDV, IDV/r

IDV/r 400/100 mg 12 .

102

.. 2553

3

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3.3.3

NRTIs

2

d4T + AZT antagonism

FTC + 3TC resistance profiles

TDF + ddI

d4T + ddI peripheral neuropathy,

pancreatitis, hyperlactatemia lactic acidosis

2

TDF + 3TC + ABC

EFV

2NNRTIs combination

unboosted SQV, DRV

ATV + IDV hyperbilirubinemia

103


3

79465_081-148_M4.indd 103 13/11/2553 19:31

3.3.4 d4Tphaseoutplan

d4T NRTIs 15

generic

d4T, 3TC NVP (

GPO-VIR S)

d4T lipoatrophy/

lipodystrophy, peripheral neuropathy, hyperlipidemia treatment

guidelines d4T list preferred ARV

regimen WHO d4T

d4T

d4T

d4T

d4T

d4T

104

.. 2553

3

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d4T

1) d4T GPO

-VIR S lipoatrophy/

lipodystrophy

viral load

50 copies/mL GPO-VIR S

TDF + 3TC + NVP TDF + 3TC + EFV

2) d4T GPO

-VIR S lipoatrophy/lipodystrophy

GPO-VIR Z viral load

50 copies/mL 12

viral load 50 copies/mL

GPO-VIR S

..2554 AZT

lipoatrophy/lipodystrophy GPO-VIR Z

6 TDF + 3TC + NVP TDF + 3TC

+ EFV

3) d4T GPO-VIR S

d4T 30 mg 60 kg

d4T

105


3

79465_081-148_M4.indd 105 13/11/2553 19:31

(nave)

GPO-VIR S (Hb

3[4a]

N

RTI

s

3TC

300

mg

24

.

15

0 m

g

12

.

CrC

l (m

L/m

in)

30-4

9 15

0 m

g

24

.

15-2

915

0 m

g

100

mg

24

.

5-14

150

mg

50

mg

24

.

6

AZT

200-

300

mg

12

.

(CrC

l 38.6 C), increasing respiratory symptoms, increasing lymphadenopathy, cutaneous lesions, ascites, CXR worsening] after initiation of HAART, tuberculoma, inflammatory bowel perforation, serositis, psoas abscess

MAC and other atypical mycobacteria

Localized lymphadenitis, necrotizing subcuta-neous nodules, endobronchial tumors, small bowel involvement, paravertebral abscesses, osteomyelitis, arthritis, focal brain lesion, Ileitis

CMV CMV retinitis despite rise in CD4 cells after initiation of HAART, immune recovery vitreitis, immune recovery uveitis, early and unusual CMV pneumonitis, pseudotumoral colitis, adenitis, encephalitis, cutaneous ulceration

Viral hepatitis (B,C) Worsening hepatitis

Parvovirus B19 Encephalitis, worsening anemia

Herpes simplex Erosive herpes simplex, encephalitis

Varicella zoster virus Acute retinal necrosis early after effective HAART regimen, increase rate of shingles after HAART

Kaposi Sarcoma (KS) Worsening KS lesion with inflammation and edema

PML Inflammatory PML variant

BK virus Hemorrhagic cystitis

3[6] IRIS

125


3

79465_081-148_M4.indd 125 13/11/2553 19:31

Cryptococcus Recurrence of meningitis early after effective HAART, pulmonary cryptococcosis, cutaneous cryptococcosis (recurrent abscesses), necrotizing mediastinal and cervical lymphadenitis, intracranial cryptococcoma, intramedullary abscess, necro-tizing pneumonitis

PCP Pneumonitis (patchy aveolar or reticulonodular infiltrates)

Skin yeasts Folliculitis

Sarcoidosis Worsening of sarcoidosis, pulmonary infiltrates, erythrema nodosum, lymphadenopathy, inter-stitial nephritis

Toxoplasmosis Encephalitis

Leshmaniasis Vitreitis, uveitis, post-Kala-Azar dermal leshmaniasis

Bartonella henselae Granulomatous splenitis

Leprosy Leprosy cutaneous lesions

Microsporidia Keratoconjunctivitis

Chlamydia trachomatis Reiters syndrome

Non infectious etiology Grave diseases, SLE, vasculitis, relapsing Guillain-Barrs syndrome, rheumatoid arthritis, polymyositis, alopecia universalis, cerebral vasculitis, hyperergic reaction (against tatoos, foreign bodies), pre-eclampsia, multiple eruptive dermatofibromas, eruptive cheilitis, peyronies disease

126

.. 2553

3

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IRIS

IRIS

cryptococcus MAC

1) IRIS paradoxical

worsening

CD4 100 cells/mm3

2-4

unmasking

corticosteroids

MDR-TB, MAC

corticos-

teroids prednisolone 30 mg/day

24-48 .

IRIS

rifampicin

IRIS prednisolone

8

IRIS

127


3

79465_081-148_M4.indd 127 13/11/2553 19:31

2) Cryptococcal meningitis IRIS

30 paradoxical worsening

localizing signs

Cryptococcal meningitis unmasking

meningitis

cryptococcal antigen

paradoxical worsening

cryptococcal meningitis


6

cryptococcal

antigen india ink cryptococcal

antigen cryptococcus india ink

meningitis


128

.. 2553

3

79465_081-148_M4.indd 128 13/11/2553 19:31

IRIS

prednisolone

lumbar puncture shunt

prednisolone

30-60 mg

prednisolone

3) Mycobacterium avium complex IRIS unmasking

MAC wasting,

chronic diarrhea, lymphadenitis non-caseating granuloma

necrosis

MAC

peritonitis

MAC

129


3

79465_081-148_M4.indd 129 13/11/2553 19:31

prednisolone 30 mg/day

prednisolone

3.8

viral load CD4 viral

load CD4


6 viral load 50 copies/mL

viral load

CD4

130

.. 2553

3

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CD4

clinical failure

viral load 6

1

1

viral load

. .

CD4

CD4

CD4

(OI prophylaxis)

CD4 6

CD4 100-150 cells/

CD4

CD4

CD4 25

50

CD4 viral load

50 copies/mL

131


3

79465_081-148_M4.indd 131 13/11/2553 19:31

* AST statin 6 12

6 rhabdomyolysis

** creatinine clearance

3[7]

CBC, CD4 6, 12 6

Viral load -

6, 12 12

( 6

)

-

3

6

12 -

FBS 6, 12 6 -

ALT* 6, 12 6 3

NNRTIs

Cr** 6, 12 6 6

TDF IDV

Lipid profile

(TC, TG, LDL, HDL)

6, 12 6 -

Urinalysis - - 6

TDF IDV

CXR - -

Pap smear 12 12

132

.. 2553

3

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3.9 (adherencetoantiretroviraltherapy)

3.9.1 adherence

1) multidisciplinary team

2)

3)

adherence

4) adherence

5)

()

6)

7) adherence

133


3

79465_081-148_M4.indd 133 13/11/2553 19:31

8) non-adherence

non-adherence

non-adherence

3.9.2 adherence

adherence 2

3[8a]

3[8b]

adherence

adherence 1

adherence

adherence

visual analogue scale, self report,

adherence

134

.. 2553

3

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adherence

30

%adherence

dose

dose

%adherence =

adherence

adherence

adherence

1

adherence

135


3

79465_081-148_M4.indd 135 13/11/2553 19:31

adherence (

)

2 adherence

fixed dose combination

adherence

adherence adherence

adherence

136

.. 2553

3

79465_081-148_M4.indd 136 13/11/2553 19:31

1.

(vira

l loa

d as

say)

g

old

stan

dard

a

dher

ence

vira

l loa

d

v

iral lo

ad

a

dher

ence

adhe

renc

e

vira

l load

(u

ndet

ec-

tabl

e leve

l)

2.

(ther

apeu

tic d

rug

mon

itorin

g)

/

a

dher

ence

12

3[8a]

a

dher

ence

/

137


3

79465_081-148_M4.indd 137 13/11/2553 19:31

3.

(DO

T)

adhe

renc

e

138

.. 2553

3

79465_081-148_M4.indd 138 13/11/2553 19:31

1.

(self r

epor

t)

2.

(pill

coun

ts)

a

dher

ence

(p

ill du

mpi

ng)

7

7

p

ill du

mpi

ng

3.

(pill

taking

rec

ord)

/

3[8b]

a

dher

ence

/

139


3

79465_081-148_M4.indd 139 13/11/2553 19:31

4.

(pha

rmac

y re

fill r

ecor

ds)

a

dher

ence

(p

ill du

mpi

ng)

5.

(elect

ronic

drug

mon

itorin

g)

M

EMS (m

edicat

ion

even

ts m

onito

ring

syst

em) c

aps

140

.. 2553

3

79465_081-148_M4.indd 140 13/11/2553 19:31

6.

(follo

w u

p ap

pointm

ent)

7.Visua

lana

logu

esc

ale

s

elf re

port

M

EMS (m

edicat

ion

even

ts m

onito

ring

syst

em) c

aps

8.

(pro

vide

r es

timat

ion)

adhe

renc

e

141


3

79465_081-148_M4.indd 141 13/11/2553 19:31

3.10 (diagnosisandmanagementoftreatmentfailure)

3.10.1

(virological failure) virological failure

virological failure

viral load

viral load

400 copies/mL 6


12 viral load

50 copies/mL viral load 50 copies/mL

6

viral load 50 copies/mL viral load

51-1,000 copies/mL

(viral blip)

genotypic resistance testing

142

.. 2553

3

79465_081-148_M4.indd 142 13/11/2553 19:31

viral load 2,000 copies/mL*

(immunologicalfailure)

CD4


viral load

Immunological failure CD4

CD4

CD4 50 cells/mm3

1 CD4 30

%CD4 3 CD4

* viral load genotyping

143


3

79465_081-148_M4.indd 143 13/11/2553 19:31

(clinicalfailure)

clinical failure virological

failure immunological failure

IRIS 3

3.10.2

144

.. 2553

3

79465_081-148_M4.indd 144 13/11/2553 19:31

1)

2)

3) adherence

4) (genotypic resistance testing)

2

5) viral

load (viral load

2)

3)

3

3 2

viral load 3

4) NNRTIs

NNRTIs NVP

EFV 2 boosted PIs (boosted PI-based

regimens)

4.1) boosted PIs LPV/r NRTIs

2

4.2) NRTIs 1 LPV/r

NRTIs 1

3TC

4.3) NRTIs

146

.. 2553

3

79465_081-148_M4.indd 146 13/11/2553 19:31

5) PIs

NRTIs PIs ( boosted)

boosted PIs new boosted PIs NRTIs

/ NNRTIs 2

3[9]

2

2NRTIs + NNRTI Boosted PI + 2NRTIs

()

2NRTIs + PI 1) New boosted PI + 2NRTIs

()

2) New boosted PI + 1NNRTI + 1NRTI

()

3) NNRTI + 2NRTIs

()

3

NRTIs 2

NNRTIs

monotherapy duo-

therapy

3[9] 2

147


3

79465_081-148_M4.indd 147 13/11/2553 19:31

1) 3


2)

3)

2

CD4

4)

NRTIs, NNRTIs, PIs boosted PIs

DRV/r

ETR (NNRTIs ) RAL ( INSTIs)

5)

3TC +/- NRTIs viral load

3TC CD4

148

.. 2553

3

79465_081-148_M4.indd 148 13/11/2553 19:31

3.11

3

1) (life-threatening adverse effects)

2) (serious adverse effects)

3) (long-term complications)

149


3

79465_149-210_M4.indd 149 13/11/2553 19:32

/

1)

(l

ife-thr

eate

ning

adv

erse

effe

cts)

Ste

vens-

Johnso

n

Syn

drom

e (S

JS)

Toxic

E

pid

erm

al

Nec

rolysis

(TEN

)

NVP

0.3

-1%

,

DLV

EFV

0.1

%,

ETR 250

cells/m

m3

0

.9%

C

D4

250

cells/

mm

3

6

.3%

C

D4 >

400

cells

/mm

3

2.3%

C

D4

400

cells/m

m3

1

-3

1

8

fulm

inan

t hep

atic fa

ilure

e

ncep

halo

path

y

50%

DRES

S s

yndr

ome

C

D4

(>25

0 ce

lls/m

m3

, >

400

cells

/

mm

3

)

A

ST

ALT

H

BV

/

HCV

NVP

C

D4

>250 cells

/mm

3

C

D4

>400 cells

/mm

3

NVP

2

NVP

A

ST

ALT

2

1

3

6

(

3TC

,

FTC

T

DF

H

BV

)

s

uppor

tive

care

N

VP

N

NR

TIs

EFV

NVP

151


3

79465_149-210_M4.indd 151 13/11/2553 19:32

/

Lacti

c

acid

osis

,

hepa

tic s

teat

osis +

/-

panc

reat

itis

(sev

ere

mito

chon

dria

l to

xici

-

ties)

N

RTI

s

d4T

ddI

A

ZT

0.85

%

50%

(

s

erum

lact

ate

>10

mm

ole/

L)

nons

pecific

gas

trointe

stinal

prod

rom

e

N

RT

I

d

4T

ddI,

AZT

BM

I

d4T

d

dI

ddI

hydro

xyur

ea

ribav

irin

d4T

ddI

d

4T

ddI

lact

ate

CO

2

anio

n ga

p

s

uppor

tive

care

IV

fluid

IV

bicar

bona

te,

hem

odia

lysis

/

hem

ofil

trati

on,

pare

nter

al n

utri-

tion

m

echa

ni-

cal v

entilat

ion

IV t

hiam

ine

/

ri

bofla

vin

seru

m

lact

ate

seru

m la

ctat

e

lact

ate

152

.. 2553

3

79465_149-210_M4.indd 152 13/11/2553 19:32

/

:

La

ctat

e

(

>5

mm

ole/

L)

Arter

ial

pH

(

/

Lacti

c

acid

osis

,

rapid

ly p

rogr

essi

ve

asce

nding

neur

omus

-

cular w

eakn

ess

d

4T

a

scen

ding

dem

yelin

ating

polyn

euro

path

y

G

uilla

in-B

arr

syn

drom

e

:

Ser

um la

ctat

e, a

nion

gap

Ar

teria

l pH, s

erum

CO

2

Cre

atine

phos

phok

inas

e

d4T

88%

69

d4T

supp

ortiv

e ca

re

lact

ic a

cido

sis

pla

smap

her

esis

,

high

dos

e co

rtico

s-

tero

id,

intrav

enou

s

imm

unoglo

bulin

,

carn

itine

ace

tylcar

-

nitin

e

d4T

154

.. 2553

3

79465_149-210_M4.indd 154 13/11/2553 19:32

/

Hyp

ers

ensit

ivit

y

reac

tion

(HSR)

ABC

8%

2

-9%

9

9

0%

6

A

BC

ABC

.

ana

phy-

laxis

H

LA-B

*570

1,

HLA

-DR7,

HLA

-DQ

3

H

SR g

rade

3

4

AB

C 6

00 m

g

24

.

300

mg

12

.

(5%

2%

)

HL

A-

B*5

701

scre

ening

A

BC

HS

R

A

BC

A

BC

vir

al

synd

rom

es

ABC

48

.

su

p-

porti

ve c

are

IV

fluid

ABC

H

SR

ABC

HLA

-B*5

70

1

scre

enin

g

H

SR

ABC

A

BC

155


3

79465_149-210_M4.indd 155 13/11/2553 19:32

/

2)

(ser

ious

adv

erse

effe

cts)

Skin

rash

N

VP

14.8

% (

1.5%

),

EFV

26%

(

grad

es 3

-4 1

%),

ABC

250

cell/m

m3

C

D4

>40

0 ce

ll/

mm

3

AST,

ALT

3-4

AST,

ALT

A

LT>5-1

0

AST,

ALT

158

.. 2553

3

79465_149-210_M4.indd 158 13/11/2553 19:32

/

Nep

hro

lith

iasis

,

urolith

iasis,

cry

stalluria

ID

V

12.4

%

4

.7-3

4.4%

AT

V

p

yuria

, he

mat

uria

,

crys

tallu

ria

seru

m

crea

tinine

neph

rolithias

is

p

eak

IDV

IDV

1.5-

2

ur

inal

ysis

seru

m cre

atini

ne

3-6

IV

fluid

ID

V

Nep

hrot

oxicity

ID

V

TD

F

IDV

T

DF

n

ephr

o-

geni

c dia

bet

es i

nsip

idus

F

anco

ni s

yn-

drom

e

IDV

TDF

TDF

C

D4

IDV

ser

um

crea

tinine,

urin

alys

is,

seru

m p

otas

sium

phos

phor

us

s

uppor

tive

care

elect

rolyte

s

159


3

79465_149-210_M4.indd 159 13/11/2553 19:32

/

:

ID

V:

Cr

,

p

yrur

ia,

hydro

nephr

osis

ren

al

atro

phy

TD

F: C

r ,

p

rote

inur

ia,

gly

cosu

ria,

hyp

oka

lem

ia,

hy

po

ph

os

ph

ate

mia

, no

n-an

ion

gap,

met

abol

ic

acid

osis

Pan

crea

titis

1-7

%

ddI

4

-5

ddI

hydr

oxyu

rea

ddI

riba

virin

d

dI

d

4T

3

TC,

d4T

TD

F

Am

ylas

e

lip

ase

in

trace

llular

/

ser

um d

dI

panc

reat

itis

hy

per

tri

glyc

erid

emia

ddI

d4T

, hy

dro

xyur

ea,

ribav

irin

ddI

TD

F

dd

I

dd

I

p

ancr

eatit

is

dd

I

d4T

, hyd

rox-

yure

a, rib

avirin

ddI

TDF

amy-

lase

lipa

se

hype

r-tri

glyc

erid

emia

panc

reat

itis

bow

el

rest

, IV

hyd

ration,

pai

n co

ntro

l, pa

rent

eral

nutri

tion

160

.. 2553

3

79465_149-210_M4.indd 160 13/11/2553 19:32

/

Ble

edin

g ep

isod

es-

incr

ease

in

he

mo-

philia

c pa

tient

s

P

Is

2-

3

PIs

hem

ophilia

NN

RT

I-b

ased

regi

men

Fact

or V

III

3)

(l

ong-

term

adv

erse

effe

cts)

Lipo

dyst

roph

y

Lip

ohyp

ertr

ophy

PI

NN

RT

I-b

as

ed

regim

ens d

4T

AZT

Li

poat

rophy

NRTI

s

d4T

A

ZT,

ddI

EFV

Lipo

hype

rtrop

hy

(dor

soce

rvical fat

pad

buffa

lo h

ump)

Lipo

atro

phy

b

aseline

BM

I

lipoa

trop

hy

injec

ta-

ble

pol

y-L-

lact

ic

acid

lipoh

yper

tro-

phy

re

stor

ative

lipoh

yper

trop

hy

recom

-bin

ant

hum

an

grow

th h

orm

one

GH-relea

s-in

g

horm

one

anal

ogue

LPV/

r

A

TV/r

vi

s-ce

ral f

at

161


3

79465_149-210_M4.indd 161 13/11/2553 19:32

/

Hyp

erlip

idem

ia

P

Is

(

unb

oost

-

ed A

TV)

4

7-75

%

d4T>

AZT

, EF

V>NVP

PIs

LDL,

TC

T

G

HDL

ATV

,

DRV,

LPV,

SQ

V b

oost

ing

RTV

d

4T

TG

LDL

TC

E

FV, N

VP

LD

L, T

C,

TG

HDL

E

FV

NVP

hy

perli

pi-

dem

ia

-P

Is: R

TV-b

oost

ed

PIs

ATV

/r

LDL,

TG

-N

NRTI

s:

PIs, EF

V>NVP

-N

RTIs

: d4T>

AZT

>ABC>T

DF

PIs

NNRTI

s

d4T

fa

sting

li-

pid

profi

le

3-6

c

ardiac

risk

fact

ors

lifes

tyle

mod

ifica

tions

hy

-

perlipi

dem

ia

N

atio

nal

Cho

lest

erol

Edu

-

catio

n Pro

gra

m

ATP III

guid

elines

162

.. 2553

3

79465_149-210_M4.indd 162 13/11/2553 19:32

/

Insu

lin re

sist

ance

/

diab

etes

mellitus

d4T,

AZT

PIs

3

-5%

p

olyu

ria,

polydi

psia

,

polyph

agia, fat

igue

hyper

gly

cem

ia

FB

S

1-3

3-6

d

4T,

AZT

N

NRTI

- ba

sed

regi

men

s

met

form

in,

glita

zone

s,

sulfo

nylure

a

insu

lin

Per

iphe

ral n

euro

path

y

dd

I 12

-34%

,

d4T

5

2%

m

onot

hera

py

neur

opat

hy

p

erip

hera

l

neur

opat

hy

a

dvan

ced

HIV

disea

se

d4T

d

dI

163


3

79465_149-210_M4.indd 163 13/11/2553 19:32

/

painfu

l neu

ropa

thy

int

race

llula

r ac

tiviti

es

ddI

TD

F,

hydr

oxyu

rea,

ribav

irin

gaba

pent

in, t

ricyc

lic

antid

epre

ssan

ts,

lam

otrig

ine,

oxyc

arba

maz

epin

e,

topi

ram

ate,

tram

adol,

na

rcot

ic a

nalg

esics,

caps

aicin

crea

m,

topi

cal l

idoc

aine

Ost

eone

cros

is

o

ld P

Is

HIV

s

ympt

o-m

atic

ost

eone

cros

is

0.0

8-1

.33%

as

ympto

mat

ic

ost

eonec

rosi

s 4%

M

RI

peria

rticul

ar p

ain

85%

fem

oral h

ead

a

dvan

ced

AID

S

s

tero

ids

hy

perlipi

dem

ia

st

eroi

d

15

%

bony

head

MRI

3-

6

1

6

1

C

onse

rvative

m

anag

emen

t:

Sur

gica

linte

rven

tion:

-E

arly

st

ages

c

ore

deco

m-

pres

sion

/

bo

ne g

rafti

ng

164

.. 2553

3

79465_149-210_M4.indd 164 13/11/2553 19:32

/

-S

ever

e

de

bil

ita

tin

g di

seas

e

to

tal

joint ar

thro

plas

ty

Car

diov

ascu

lar

effec

ts, includ

ing

myo

card

ial

infa

rctio

n

(MI),

cer

ebro

vasc

ular

accide

nts

(CVA

)

M

I

CVA

P

Is

M

I

A

BC

ddI

o

bser

vatio

nal

stud

ies

rand

omized

stu

dies

M

I

0

.3-0

.6%

C

VA

0.1

%

co

rona

ry

arte

ry d

isea

se

cere

brov

ascu

lar ac

cide

nts

c

ardi

ovas

-

cula

r dis

ease

h

yper

lipid

emia

c

oron

ary

arte

ry d

isea

se

p

rem

atur

e

coro

nary

art

ery

dise

ase

c

ardi

ac

risk

fact

ors

hype

rlipi

dem

ia

hype

rglyce

mia

lifes

tyle

mod

ifica

tion

h

yper

lipid

emia,

hyp

ert

en

sio

n,

insu

lin r

esista

nce/

diab

etes

mellitus

c

ardi

ac

risk

fact

ors

lif

esty

le

mod

ifica

tions

c

ardi

ovas

-

cula

r eff

ects

N

NR

TI

ATV-

base

d re

gim

en

d4T

165


3

79465_149-210_M4.indd 165 13/11/2553 19:32

3.12

3.12.1

2

(AIDS-defining neoplasms) Kaposis

sarcoma Burkitts immunoblastic

2 2

non-Hodgkins

(primary central nervous system lymphoma)

invasive

CD4 2

Hodgkins

primary effusion lymphoma, plasmablastic lymphoma

basal cell carcinoma seminoma

Hodgkins leiomyosarcoma

166

.. 2553

3

79465_149-210_M4.indd 166 13/11/2553 19:32

CD4 viral load

Kaposis sarcoma Burkitts immunoblastic

2

invasive

Hodgkin's non-small cell

CD4

CD4

200 cells/mm3

CD4 200 cells/mm3

167


3

79465_149-210_M4.indd 167 13/11/2553 19:32

3.12.2

3[11]

AZT peripheral neuropathy

d4T ddI

HBV,

HCV

168

.. 2553

3

79465_149-210_M4.indd 168 13/11/2553 19:32

vira

l loa

d

2

-3

(ele

ctiv

e)

N

NRTI

N

NRTI

s 7-

10

NRTI

s

N

NRTI

s

b

oost

ed P

Is 7

-10

P

Is

3[1

1]

169


3

79465_149-210_M4.indd 169 13/11/2553 19:32

3.12.3

TDF, 3TC, EFV

3[12] TDF viral load 50

copies/mL HBV (HBsAg)

EFV

1-2

170

.. 2553

3

79465_149-210_M4.indd 170 13/11/2553 19:32

EFV

EFV

NVP

N

VP 4

00 m

g

24

.

LPV/

r

LPV/

r

12

.

24

.

A

TV/r

IDV/

r

L

PV/

r

24

.

A

TV/r

TDF

TDF

ddI

ddI

1

.

2

.

AZT

d4T

A

ZT

d

4T

12

.

T

DF

24

.

vira

l load

12-59

Booster 12-18 2

4[1b] Hib(7)

217


4

79465_211-292_M4.indd 217 13/11/2553 20:57

(1) BCG

(2) HBV

DTP-HBV 2, 4, 6

(3) DTP DTwP DTaP (Tdap)

1

(4) Polio vaccine IPV OPV IPV

(5) MMR (clinical stage C %CD4

15) MMR2 1 MMR1

4-6

(6) JE 1 3 4-5

(7) Hib 2

1 12-18

2

4[1b]

218

.. 2553

4

79465_211-292_M4.indd 218 13/11/2553 20:57

(8) HAV 1 2

6-12

(9) VAR 1 %CD4 15 2

3

(10) Influenza vaccine

9 2

1

(11) PCV 2 3 2

12-15 4[1c]

PS23 2 PCV

2 PS23 1 5

(12) HPV 3 0, 1-2, 6 9

26

219


4

79465_211-292_M4.indd 219 13/11/2553 20:57

4[2a]

4[2b]

6

%CD4 15

220

.. 2553

4

79465_211-292_M4.indd 220 13/11/2553 20:57

1 0 dT1, OPV/IPV1, MMR, BCG

2 1 HBV1, JE1

3 2 dT2, JE2, OPV/IPV2, HBV2

4 7 HBV3

5 12 dT3, OPV/IPV3, JE3

1 0 DTP1, OPV/IPV1, Measles/MMR, BCG

2 1 HBV1, JE1

3 2 DTP2, OPV/IPV2, JE2

4 4 DTP3, OPV/IPV3, HBV2

5 8 HBV3

6 12 DTP4, OPV/IPV4, JE3

4[2a] 1-6

4[2b] 7-18

221


4

79465_211-292_M4.indd 221 13/11/2553 20:57

PCP

PCP

2-3 (

)

PCP CD4

co-trimoxazole (TMP-SMX) 150 mg/m2

TMP 1-2 3

TMP-SMX

46 PCP

6

12

12

12 %CD4 15

TMP-SMX dapsone

2 mg/kg ( 100 mg) 4 mg/kg ( 200

mg) desensitization

TMP-SMX

222

.. 2553

4

79465_211-292_M4.indd 222 13/11/2553 20:57

PPD skin test

223


4

79465_211-292_M4.indd 223 13/11/2553 20:57

4.1.3

PCP

224

.. 2553

4

79465_211-292_M4.indd 224 13/11/2553 20:57

PCR 1-2

1

PCR1-2

PCR2

PCR1-2

42

anti-HIVPCR

18anti-HIV

anti-HIV12

5-10antibody

anti-HIV

12

anti-HIV18

antibody antigen

(HIV Ag/Ab)

antibody 18

PCR

225


4

79465_211-292_M4.indd 225 15/11/2553 10:43

antibody18

antibody

antibodyantibody24

(definitive exclusion of

HIV infection)

1) PCR2

1

4

2) anti-HIV6

2

3) PCR 1 4

anti-HIV16

CD4

226

..2553

4

79465_211-292_M4.indd 226 15/11/2553 10:43

(presumptive exclusion

of HIV infection)

1) PCR2

14

1

2) PCR1

2

3) anti-HIV 6

1

CD4

227


4

79465_211-292_M4.indd 227 15/11/2553 10:43

4.2 (ARV therapy in nave HIV-infected children)

4.2.1

1) (medicalevaluation)

1.1)

IRIS

latentTBinfection

1.2) CD4

228

..2553

4

79465_211-292_M4.indd 228 15/11/2553 10:43

TMP-SMX

TMP-SMX

1.3)

CBC,ALT,AST,CD4CD4

CD4 viral load

CXRPPDskin test

PPD

skin test

HBsAg

2)

(ARV counseling)

2.1)

229


4

79465_211-292_M4.indd 229 15/11/2553 10:43

2.2) ( 6)

2.3)

2.4)

3)

(adherence counseling)

4.10

4.2.2

1)

230

..2553

4

79465_211-292_M4.indd 230 15/11/2553 10:43

(symptomatic)

1

1

1

CD4

2)

2

2.1) CDCclassificationsystem..2537

categoryA,BC

CDCcategoryBC

2.2) WHOstagingsystem..

2549WHOstage1,2,34

WHOstage34

WHOstage12720

3) CD4 %CD4HIVprognostic

markercollaborative

4,000

2,500CD4%CD4

CD4%CD44[3]

231


4

79465_211-292_M4.indd 231 15/11/2553 10:43

- CD4%CD4CD4%CD4

CD4

-

CD4 %CD4

CD4

%CD4

< 1 1- 5 > 5

CDC

categoryB,C

WHO

stage3,4

CDCcategoryB,C

WHOstage3,4

CD4

%CD4

CD4

CD4

%CD425 CD4350cells/mm3

4[3]

1(12-monthmortalityrisk)

CD4%CD4

CD4%CD4

CD4%CD46

232

..2553

4

79465_211-292_M4.indd 232 15/11/2553 10:43

NRTIs AZT + 3TC d4T + 3TC

AZT+3TCd4T+3TC

lipodystrophy

(Hb 3

(preferred regimens)

AZT+3TC+NVP AZT+3TC+EFV

(alternative regimens)

d4T+3TC+NVP AZT+3TC+NVP

d4T+3TC+EFV

d4T+3TC+NVP

4.2.3 (antitretroviral nave)

233


4

79465_211-292_M4.indd 233 15/11/2553 10:43

NVP

d4T+3TC+NVP(GPO-VIRS)AZT+3TC+NVP

(GPO-VIRZ250)

15hypersensitivity

4.2.4 NVP 12

NVP

NNRTIs 20-57

2NRTIs+PI

NVPNVPEFV

NNRTIsNVP

2NRTIs + PI

(preferred regimens)

AZT+3TC+LPV/r

(alternative regimens)

d4T+3TC+LPV/r

NNRTI NVP EFV

EFV 3 EFV

234

..2553

4

79465_211-292_M4.indd 234 15/11/2553 10:43

NNRTIs2NRTIs+LPV/r

12viralloadLPV/r

NNRTIs viral load 6

LPV/r

NVP

1

2NRTIs+PI2NRTIs+NNRTI

2NRTIs+NNRTIviral

load6viralload

PI

4.2.5 (antiretroviral therapy in children with opportunistic infection)

IRISCD4

CD4

IRIS20

235


4

79465_211-292_M4.indd 235 15/11/2553 10:43

2

TB,MAC,PCP,cryptococcosis

cryptosporidiosis,microsporidiosis

2-8

8

(CD4)

236

..2553

4

79465_211-292_M4.indd 236 15/11/2553 10:43

Rifampicin

NNRTIs PIs

PIs

NNRTIs

CXR PPD skin test

supporting evidence

INH

10mg/kg/day9PPDskintest

1) CD4

2) CD4

2-8

IRIS

CD4 CD4

237


4

79465_211-292_M4.indd 237 15/11/2553 10:43

1) NNRTIs

(rifampicin)EFVEFV

25

EFVEFV3

EFVNVP

2) NNRTIs PIs

2.1)

rifampicin quinolones

aminoglycosidePIs

2.2)

rifampicin2

maintenance

rifampicin PIs

PIs rifampicin

2(rifampicin

)

3) NNRTIs

tripleNRTIsAZTd4T+3TC+ABC

rifampicin

NNRTIs

PIsABC

238

..2553

4

79465_211-292_M4.indd 238 15/11/2553 10:43

NNRTIs

NVP

PIs

PIsPIs

2 (induction period)

PIs maintenance rifampicin

rifampicin

quinolones aminoglycoside

PIs

239


4

79465_211-292_M4.indd 239 15/11/2553 10:43

4.3

4.3.1

2-3

2-3

1) (newclinicalevents)

IRIS

2)

(secondarysexcharacteristics)

3) (neurodevelopment)

(OFC) 2

4.3.2

1) (safetymonitoring)

1.1) CBC6AZT

3

WBC

240

..2553

4

79465_211-292_M4.indd 240 15/11/2553 10:43

1.2) Chemistryliverenzyme,renalfunction,

lipidprofile6

NVPALT2-4

IDVTDF

urineanalysis(IDVWBC,RBC

TDFglucosuria,proteinuria)creatinine

2-3

2) (immunological and virological

monitoring)

2.1) CD4%CD4

6

2.2) viral load

6

viral load 6 1

CD4 %CD4

viralload

241


4

79465_211-292_M4.indd 241 15/11/2553 10:43

1)

Mito

chon

dria

l dys

func

tion

Lacticacido

sis

N

RTIs

d4T

,dd

I

4

1-20

:

:

:

metab

olic

acidos

is

anion

ga

p>1

6

se

rumla

ctate>5

mmol/L

routine

serumla

ctate

bicarbo

nate

thiam

ine,

ribofl

avin,oralantioxida

nt

(L-carnitin

e,coe

nzym

eQ,

vitaminC

)

NRTIs

TDF

ABC

AZT

3TC

se

rumla

ctate

fluo

ride-ox

alate

tube

la

b

4

.

4[4

]

4.4

242

..2553

4

79465_211-292_M4.indd 242 15/11/2553 10:43

Pan

crea

titis

N

RTIs

ddI,

d4T

3TC

Serum

amylas

e

lipas

e

routine

serumamylas

e

lipas

e

se

rum

amylas

e

NRTIs

panc

reatitis

AZT

ABC

ddI

d4T

Periphe

ral

neurop

athy

d4T,ddI

hyp

orefl

exia

(

the

rape

uticran

ge)

N

RTIs

AZT

ABC

243


4

79465_211-292_M4.indd 243 15/11/2553 10:43

2)

Met

abol

ic a

bnor

mal

ity

Fatmaldistrib

ution

N

RTIs

d4T

P

Is

boo

sted

PIs

lipoh

ypertro

phy

P

Is

lipoh

ypertro

phy

(

)

lipoa

troph

y

N

RTIs

d4T

dd

I

AZT

d4T,A

ZTA

BC,

TDF

244

..2553

4

79465_211-292_M4.indd 244 15/11/2553 10:43

Hyp

erglyc

emia

insu

linresistan

ce

P

Is

FB

S>

126mg/dL

rand

omblood

su

gar

20

0mg/

dL

FBS

OGTT

P

Is

FB

S

rand

omblood

suga

r

FBS

6

Hyp

erlip

idem

ia

P

Is

N

NRTIs

EFV

hype

rlipide

mia

NVP

Cho

lesterol,LD

L

athe

rosc

lerosis

TG

panc

reatitis

Fa

sting

choles

terol

>200

mg/dL

Fa

stingLD

L

>130

mg/dL

Fa

stingTG

>200

mg/dL

Fa

sting

choles

terol,

HDL,LDL

TG

6

6-12

pan

crea

titis

TG

>500

mg/dL

P

Is

NNRTIs

NNRTIs

ATV

245


4

79465_211-292_M4.indd 245 15/11/2553 10:43

cho

lest

erol

statin

-Prava

statin(

2,000 copies/mL**

genotyping

adherence

262

..2553

4

79465_211-292_M4.indd 262 15/11/2553 10:43

4.7.1 genotyping

1) genotyping

viralload2,000copies/mL

1

2) NRTIs3TC

(mutation) Thymidine Analog

Mutations(TAMs)TAMs4NRTIs

NRTIsTAMs

4NRTIsTDF,ddIABC

multi-NRTImutation(Q151M,69i)NRTIs

(Q151MTDF)K65RTDF

NRTIs

boostedPIsNRTIs

3) 3TC

NRTIsM184V

M184I3TC3TC

M184V(lessviralfitness)

263


4

79465_211-292_M4.indd 263 15/11/2553 10:43

4) genotyping

noevidenceofresistance,possibleresistanceresistance

mutationsgenotyping

4[6a]

possibleresistanceresistance

NRTIs

(recycle)

264

..2553

4

79465_211-292_M4.indd 264 15/11/2553 10:43

4[6

a]

ge

notyping

NRTIs

(

)

NRTI

s

M

utat

ions

NRTI

s

AZT

d4T

-TA

Ms:M

41L,D

67N,K70

R,

L210

W,T2

15YF

,K21

9QE

-Multi-NRTI:Q15

1M

complex

(A62

V,V75

I,F7

7L,

F116

Y,Q

151M

),69

inse

rtion

-

TAMs

NNRTIs

Mutations

NVP,EFV Y181C/I,K103N,G190S/A,

L100I,V106M/A,V108I,

Y188CLH,P225H

mutation

NVPEFV

4.7.2 genotyping PIs

PIsNRTIs

NNRTIsPIsRTV

(boosting)PIsPIs

PIs2

1) mutationmajormutation

minormutationPIs

majormutationcrossresistance

LPV/rRTV

4[6b] genotypingNNRTIs

NNRTIs ETR

mutation score Update of the Drug Resistance

MutationsinHIV-1NVPEFVmutation

scoreETR

266

..2553

4

79465_211-292_M4.indd 266 15/11/2553 10:43

2) mutation

mutation5

mutation

(geneticbarrier)

DRV/r

4.7.3 2NRTIs + 1NNRTI

2NRTIs+

1NNRTI(NVPEFV)

1) :2NRTIs(

genotyping)+LPV/r

2) :

2.1) 2NRTIs ( genotyping) +

ATV/rATV

6

2.2) Double-boostedPIsLPV/r+

SQVLPV/r+IDV

NRTIsNRTIs

NNRTIs

TDF

267


4

79465_211-292_M4.indd 267 15/11/2553 10:43

adherence

double-boostedPIs

double-boostedPIs viral suppression

1

boosted PI +

2NRTIs/3NRTIs

1 NRTIs

2NRTIsresistancetesting

4[4](

2NRTIsAZT+d4T,d4T+ddI,TDF+ddI)

1: mutation TAMs

4NRTIs

(recyclingNRTIs)ddI+AZT,ddI+3TC,ABC+3TC,ABC+ddI

268

..2553

4

79465_211-292_M4.indd 268 15/11/2553 10:43

2: TDF

mutation TAMs 4

Q151M69iK65R

1230kgTDF

TDF+3TC,TDF+ABCTDF+AZT

AZTNRTI3TDF+3TC+AZTTDF+ABC+

AZTAZTK65R

TDF

3: TDF

mutation TAMs 4

Q151M69iK65R

NRTIsNRTIs

ddI+ABC,ddI+3TCddI+AZT

NRTIsdouble-boostedPIs

3TC

269


4

79465_211-292_M4.indd 269 15/11/2553 10:43

4[7a] NRTIs

NRTI

TDF

- TAMs

-

-

-

30 kg

Tannerstage>4

ABC -

lipodystrophy

-

-

-hypersensitivity

6ABC

HLA-B*5701 genotype

HLA-B*5701

ABC

-

TDF2553

www.ClinicalTrial.govNCT00352053www.ClinicalTrial.govNCT00528957

270

..2553

4

79465_211-292_M4.indd 270 15/11/2553 10:43

2 PI

LPV/r

PIIDV/r

LPV/r

3 double-

boostedPIsLPV/rIDVSQV

4[7b]PIs

PI

LPV/r

-

-

-PIRTV

-

-

-43%

-

271


4

79465_211-292_M4.indd 271 15/11/2553 10:43

PI

ATV/r -RTV

ATV

-

->6

-

LPV/rIDV/r

-

-RTV

-

-

conductionsystemdefect

prolongedPRinterval

-indirecthyperbiliru-

binemia

SQV/r

-RTV

SQV

-

-

LPV/rIDV

-LPV/r

doubleboostedPIs

-

-RTV

-

-

-double

boostedPIs

PIs

-50mg/kg12.

272

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PI

IDV/r -RTV

IDV

-

-LPV/r

doubleboostedPIs

-

-RTV

-

-double

boostedPIs

PIs

-220-300mg/m2

12.

-

2

trough0.1g/L

2.

10g/L

273


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4[4]

viral load 3-6

- single boosted PI NRTIs

ddI + ABC, ddI + 3TC ddI + AZT

LPV/r ATV/r

- double-boosted PIs

LPV/r + SQV LPV/r + IDV

3TC, AZT + 3TC, ABC + 3TC

1 boosted PI

: LPV/r

: ATV/r

TDF + 3TC TDF + ABC TDF + AZT

AZT NRTI 3

TDF + 3TC + AZT TDF + ABC + AZT

ddI + 3TC, ddI + AZT,

ABC + 3TC, ABC + ddI

>12

>30 kg

TDF + 3TC,TDF + AZT,

TDF + ABC

3

TAMs >4 69i

K65R

30 kg

2 NRTIs

2 2NRTIs genotype + 1 boosted PI

genotyping

viral load >2,000 copies/mL*

6

d4T AZT + 3TC + NVP EFV

*viralloadgenotyping

274

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4.7.4 3 NRTIs, NNRTIs PIs

3

2

genotypicresistance

testing

FTC(NNRTI),

DRV/r(PI),RAL(INSTI),maraviroc(CCR5inhibitor)

DRV/r 6

viralload6viralload

1,000copies/mL

CD4

NNRTIs

NNRTI CD4

3TC

mutation CD4

(3)

4.7.5 NRTIs 2 (dual NRTIs therapy)

1-2

NRTIs

275


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viralload50copies/mL2NRTIs+

1NNRTI viral load genotypic resistance

testing4.7.6

4.7.6 dual NRTIs

1) 2NRTIsgenotyping+boostedPI

NRTIsPIs

2NRTIs+1NNRTI

2) 2

2.1) 2NRTIs + 1NNRTITAMs

4 multi-NRTI mutation

NNRTIsNRTIs

2.2) NNRTI + booosted PI + 1NRTI/2NRTIs(recycle)

NRTIs

TAMs4multi-NRTImutation

NNRTIsPIs

276

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4.7.7

1) 1

3

adherencePIsmetabolic

lipidprofile2TDF

IDVurinalysis,Cr*bloodsugar6

CrCl50mL/minTDF

2) 1

32-3CD4

3-66viralload

6

viral load1,000copies/mL6

3)

PIs 2

PIs

double-boostedPIs

IDV/rSQV/r25kg

PIs2

*creatinineclearance

277


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4.8

T cell B cell

CD4

%CD415

%CD425CD4350cells/mm3

(>5)6%CD415viral

suppression400copies/mL1

4[8]

CD4

278

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%CD415

4[8]

%CD415

*

**MMR

1 2 6

HBVvaccine HBV1 HBV2 HBV3 3

JEvaccine* JE1 JE2 2

Measlesvaccine** MMR1 1

dTvaccine

>710

279


4

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4.9

4.9.1

41)2)

3)

4)

4.9.2

10

280

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4.10 (adherence to antiretroviral treatment in children)

adherence

95

adherence

5

1 :

281


4

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2 :

1-2

DOT

TMP-SMX

2-4

3 :

(fixeddosecombination)

TDF+3TC+EFV

4 :

5

:adherence

282

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4.11

(5Ds)

D1-Disclosure :

9-10

1)

2)3)

4)

5)

D2-Depression : 13

283


4

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D3-Drug :

D4-Dangers :

9-12

12-14

D5-Daily activity :

284

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Documents

Thai Guideline on HIV Diagnosis and Treatment