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2557

Thailand National Guidelines onHIV/AIDS

Treatment and Prevention 2014

2 2557

3Thailand National Guidelines on HIV/AIDS Treatment and Prevention 2014

2557

Thailand National Guidelines on HIV/AIDS Treatment and Prevention 2014

.

.

. .

..

..

..

..

..

..

..

..

..

.

.

.

. -

. -

.

-

4 2557

.

.

. -

. -

.

.

.

1

2557 7,450


.. 2553

.. 2557

/

.. 2553

2557

CD4

2557

.. 2553

2557

6 2557


1 (Introduction) 25

2 35

(HIV Laboratory for Diagnostic and Monitoring)

2.1 36

2.2 40

2.2.1 HIV viral testing 40

2.2.2 41

2.3 55

2.3.1 CD4 (CD4 count) 55

2.3.2 (HIV viral load) 57

2.3.3 (HIV drug resistance testing) 58

2.4 61

3 (Management of HIV-Infected Adult) 65

3.1 66 3.2 72

3.3 73

3.4 75

3.5 77

3.5.1 77

3.5.2 78

(Multi-class antiretroviral treatment failure)

3.6 80

3.7 82

3.8 (Drug-drug interaction) 83

3.9 100

3.9.1 100

3.9.2 ( OIs 6) 102

8 2557

3.9.3 106

3.9.4 107

3.9.5 108

3.10 109

3.11 110

3.12 115

3.12.1 128

()

3.13 131

(Adherence to antiretroviral therapy)

3.13.1 adherence 131

3.13.2 adherence 132

3.14 Immune reconstitution inflammatory syndrome (IRIS) 137

3.15 141

3.15.1 141

(acute HIV infection)

6 (recent HIV infection)

3.15.2 143

3.15.3 148

3.15.4 150

3.15.5 154

3.15.6 156

3.15.7 158

3.15.8 159

3.16 162

3.17 (Treatment as Prevention) 165

3.18 166


4 169

(Management of HIV-Infected Children and Adolescent)

4.1 170

4.1.1 170

4.1.2 171

4.1.3 178

4.2 181

4.2.1 182

4.2.2 185

4.2.3 188

4.2.4 189

3

4.2.5 190

4.3 194

4.3.1 194

4.3.2 195

4.3.3 196

4.4 197

4.5 208

(Immune reconstitution inflammatory syndrome: IRIS)

4.6 212

4.6.1 212

4.6.2 215

10

2557

4.7 216

4.7.1 218

HIV genotyping

4.7.2 220

2NRTIs + 1NNRTI

4.7.3 221

2NRTIs + 1PI

4.7.4 3 NRTIs, NNRTIs 223

PIs

4.7.5 225

4.8 226

4.9 228

4.10 230

4.11 231

4.12 234

4.13 234

4.14 236

5 237

(Prevention of Mother-to-Child HIV Transmission)

5.1 239

5.1.1 240

5.1.2 242

5.2 245

5.3 250

11


5.3.1 251

5.3.2 253

5.3.3 258

5.3.4 259

(no ANC)

5.3.5 262

5.4 267

5.5 270

5.5.1 270

5.5.2 270

5.6 272

5.7 272

5.7.1 272

5.7.2 274

5.8 275

(Early infant diagnosis EID)

6 277

(Opportunistic Infections: Prophylaxis and Treatment)

6.1 (Tuberculosis) 278

6.2 293

6.2.1 Pneumocystis pneumonia (PCP) 294 6.2.2 Cryptococcosis 298

6.2.3 Candidiasis 302

6.2.4 Toxoplasmic encephalitis 305

6.2.5 Penicilliosis histoplasmosis 309

6.2.6 Cytomegalovirus (CMV) infection 312

6.2.7 Mycobacterium avium complex (MAC) infection 315

12

2557

7 (HIV Prevention) 333

7.1 334

(Antiretroviral-based HIV prevention)

7.1.1 (Treatment as Prevention) 334

7.1.2 337

(Pre-Exposure Prophylaxis)

7.1.3 341

(Post-Exposure Prophylaxis)

7.2 (Male circumcision) 351

7.3 356

7.4 360

7.5 367

8 369

(Service Delivery Guidance)

8.1 (Recruit) 371

8.2 (Test) 379

8.3 (Treat) 386

8.4 (Retain) 389

8.5 402

8.6 410

13


417

422

(Dose and Route of HIV Medication in Adults)

CDC Classification 432

438

(WHO Classification System for HIV-Infected Children)

441

(Dose and Route of HIV Medication in Pediatrics)

creatinine clearance 450

451

rapid desensitization TMP-SMX 456

457

475

2557


14

2557

2.1 42

2.2 42

99.5

99.0

2.3 61

2.4 63

2.5 64

3.1 68

3.2 70

3.3 72

3.4 73

CD4 >500 cells/mm3

3.5 74

3.6 75

3.7 virological failure 77

3.8 79

3.9 79

3.10 81

3.11 87

3.12 NNRTIs, RAL, and PIs 97

15


3.13 111

3.14 114

3.15 116

3.16 130

3.17 adherence / 134

3.18 adherence / 135

3.19 137

Immune reconstitution inflammatory syndrome IRIS

3.20 IRIS 138

3.21 IRIS 140

3.22 acute HIV infection 143

3.23 144

3.24 147

3.25 149

3.26 157

3.27 PIs methadone 158

3.28 163

4.1 172

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4.2 1-6 177

4.3 7-18 178

16

2557

4.4 187

4.5 188

4.6 197

4.7 222

4.8 227

%CD4 < 15%

5.1 240

5.2 244

5.3 251

5.4 HAART 252

5.5 254

5.6 265

5.7 267

5.8 268

HAART

5.9 100 g OGTT 269

5.10 275

6.1 319

6.2 324

17


6.3 CD4 330

6.4 CD4 331

7.1 PrEP 337

adherence

7.2 HIV oPEP 345

HIV oPEP

7.3 HIV oPEP HIV nPEP 346

7.4 347

7.5 HIV nPEP 349

7.6 nPEP nPEP 350

8.1 396

8.2 399

8.3 411

1. 422

2. 435

CD4

3. (staging) 436

4. 437

5. 441

6. rapid desensitization TMP-SMX 456

18

2557

2.1 37

2.2 44

18

2.3 52

18

2.4 60

3.1 Crypto Ag 105

3.2 129

4.1 IRIS 210

4.2 215

4.3 217

5.1 247

5.2 248

7.1 335

7.2 body fluids 344

8.1 370

8.2 376

8.3 378

8.4 390

8.5 405

8.6 409

8.7 412

19


/r Ritonavir boosted3TC LamivadineABC AbacavirATV AtazanavirAZT ZidovudineCCBs Calcium channel blockersCOBI Cobicistatd4T StavudineDCCBs Dihydropyridine calcium channel blockersddl DidanosineDMPA Depot medroxyprogesterone acetateDRV DarunavirDTG DolutegravirE EthambutolEE Ethinyl estradiolENG EtonogestrelEFV EfavirenzETR EtravirineEVG ElvitegravirFTC EmtricitabineHRAs H2-receptor antagonistsIDV Indinavir

20

2557

LNG LevonorgestrelINH, H, I IsoniazidLPV/r Lopinavir/ritonavirMVC MaravirocNET NorethindroneNFV NelfinavirNGM NorgestimateNRTI Nucleoside reverse transcriptase inhibitorNSAIDs Nonsteroidal anti-inflammatory drugsNVP NevirapinePAS Para-aminosalicylic acidPI Protease inhibitorPPIs Proton pump inhibitorsPZA, Z PyrazinamideR RifampicinRAL RaltegravirRPV RilpivirineRTV RitonavirSQV SaquinavirTCAs Tricyclic antidepressantsTDF TenofovirTMP TrimethoprimTMP-SMX Trimethoprim/sulfamethoxazole

21


BCG Bacillus Calmette-GurinDT/dT Diphtherias, tetanus vaccineDTaP/Tdap Diphtherias, tetanus, acellular pertussis vaccineDTP Diphtherias, tetanus, pertussis vaccineDTwP Diphtheria, tetanus, whole cell pertussis vaccineHAV Hepatitis A vaccineHBV Hepatitis B vaccineHib Haemophilus influenza type B vaccineHPV Human papillomavirus vaccineIPV Injection polio vaccineJE Japanese encephalitis vaccineMMR Measles, mumps, rubella vaccineOPV Oral polio vaccinePCV Pneumococcal conjugate vaccinePPSV-23 23-valent pneumococcal polysaccharide vaccinePRP-T Polyribose ribital phosphate-tetanus toxoidTd Tetanus and diphtheria toxoidTT Tetanus toxoidVZV Varicella-zoster virus vaccine

22

2557

AFB Acid-fast bacilliAHI Acute HIV infectionALT Alanine aminotransferaseARS Acute retroviral syndromeAST Aspartate aminotransferaseAUC Area under the curveBMD Bone mineral densityBMI Body mass indexCBC Complete blood countCD4 Cluster of DifferentiationCITC Client-initiated testing and counselingCMV CytomegalovirusCrCl Creatinine clearanceCT Chlamydia trachomatisCXR Chest x-rayDOT Directly observed therapyDSC Disease specific certificationDXA Dual energy x-ray absorptionmetryEBV Ebstein-Barr virusEID Early infant diagnosisEM Erythema multiformeEWI Early warning indicatorsFBS Fasting blood sugarFDA Food and Drug AdministrationGCT Glucose challenge testHAART Highly active antiretroviral therapy

23


HAV Hepatitis A virusHBV Hepatitis B virusHct HematocritHCT HIV counseling and testingHCV Hepatitis C virusHDL High-density lipoproteinHHV Human herpes virusHPV Human papillomavirusIGRA Interferon gamma release assayINR International normalised ratioIPT Isoniazid preventive therapyIRIS Immune reconstitution inflammatory syndromeIRS Immune restoration syndromeIUD Intrauterine deviceIUI Intrauterine inseminationIVF In vitro fertilizationLDL Low-density lipoproteinMAC Mycobacterium avium complexMEMS Medication events monitoring systemMMT Methadone maintenance treatmentNAT Nucleic acid testingNTM Nontuberculous mycobacteriaOGTT Oral glucose tolerance testOI Opportunistic infectionPCP Pneumocystis carinii pneumoniaPCR Polymerase chain reaction

24

2557

PDCA Plan do check actPEP Post-Exposure ProphylaxisPITC Provider-initiated testing and counselingPML Progressive multifocol leukoencephalopathyPMTCT Prevention of mother-to-child transmissionPrEP Pre-Exposure ProphylaxisPwP Prevention with positivesRPR Rapid plasma reaginSDR Same day resultSJS Stevens Jonhson syndromeTAMs Thymidine analog mutationsTasP Treatment as PreventionTB TuberculosisTEN Major/Toxic epidermal necrolysisTG TriglycerideTLTI Treatment latent tuberculous infectionTST Tuberculin skin test UIC Unified identification codeUNAIDS UP Universal precautionVCT Voluntary counseling and testingVDRL Venereal disease research laboratory testVL Viral loadWHO World Health Organization.


25

1Introduction

.. 2527

.. 2557 1,175,084

431,475 8,535

.. 2556 286,214

.. 2547 (58,133 )

30

CD4 200 350

cells/mm3 1 2555 5 2556

1.

(

)

2.

( CD4)

3.

4.

1(Introduction)

2557

26

1

CD4 100 cells/mm3

CD4 CD4

CD4

2555

(treatment as prevention)

(early diagnosis

and early treatment)

90 (key

populations; KPs) (same day

result HIV testing)

(PMTCT option B+)


27

1Introduction

(pre-exposure prophylaxis; PrEP)

(prevention and care

continuum)

(task shifting/task sharing)

2557

2557

28

1

2557

2

(HIV Laboratory for Diagnosis and Monitoring)

-

- algorithm

rapid test algorithm

- window period 3

1

- (indeterminate)

(inconclusive)

2 / 1 3

inconclusive 3

- DNA PCR

EDTA

(dried blood spot; DBS)

- HIV DNA PCR

HIV DNA PCR


29

1Introduction

3

(Management of HIV-Infected Adult)

-

CD4 CD4 < 500 cells/mm3

- NRTIs + NNRTI

TDF/3TC TDF/FTC EFV

- NRTIs

ABC + 3TC AZT + 3TC

- VL > 1,000 copies/mL

VL > 50 < 1,000 copies/mL

VL 2-3

2557

30

1

4

(Management of HIV-Infected Children and Adolescent)

- < 1

CD4, %CD4

- 1 (CDC category B, C

WHO stage 3, 4) CD4

- CD4

o 1-< 3 %CD4 < 25% CD4

< 1,000 cells/mm3

o 3-< 5 %CD4 < 25% CD4

< 750 cells/mm3

o 5-15 CD4 < 350 cells/mm3

CD4 350-500 cells/mm3

2 nucleoside reverse transcriptase inhibitors (NRTIs) + NNRTI Boosted PI

2NRTIs

o 12 AZT/3TC ABC/3TC

o > 12 TDF/3TC

NNRTIboostedPI

o < 3 LPV/r

o 3 EFV

- HIV viral load testing

VL > 1,000 copies/mL

HIV drug resistance testing

-


31

1Introduction

5

(Prevention of Mother-to-Child HIV Transmission)

2553 2557

CD4 350 cells/mm3

CD4 > 350 cells/mm3

14

CD4

: AZT + 3TC + LPV/r : TDF + 3TC + EFV

: AZT TDF + 3TC + LPV/r

CD4 350 cells/mm3

CD4 > 350 cells/mm3

discordant couple,

(HAART) > 4

50 copies/mL

4

> 50 copies/mL

: AZT x 4

: AZT + 3TC +

NVP x 4-6

: AZT x 4

: AZT + 3TC + NVP

x 6

2557

32

1

2553 2557

(elective caesarean

section)

latent phase

of labor

4 .

DNA

PCR 2 1-2

4-6

anti HIV 12-18

: 2 1

2-4

: 3 1, 2

4

TSH

TSH

anti-HIV 18

1

4-6


33

1Introduction

6

(Opportunistic Infections: Prophylaxis and Treatment)

-

-

CD4

o CD4 50 cells/mm3 2

o CD4 > 50 cells/mm3

2 2-8

- rifampicin EFV

EFV NVP RAL

- protease inhibitor

rifampicin

- primary prophylaxis cryptococcosis, penicilliosis,

histoplasmosis Mycobacterium avium complex (MAC)

-

-

2557

34

1

7 (HIV Prevention)

7

8

(Service Delivery Guidance)

treatment cascade

(

)

VL

1 VL < 50 copies/mL

recruit-test-treat-retain (--

-)


35

2HIV Laboratory for Diagnosis and Monitoring

.. 2555-2559

1)

2) 3)

CD4

(VL)

2

(HIV Laboratory for Diagnostic and Monitoring)

2557

36

2

2.1

(voluntary counseling and testing; VCT)

(pre-test/

post-test counseling) 2.1

(group counseling)

(individual counseling)

2

(client-initiated

testing and counseling; CITC) (provider-initiated

testing and counseling; PITC) PITC

(WHO) (UNAIDS)


37


2.1

(pre-test counseling)

(ongoing counseling)

()

CITC

PITC

2557

38

2

(same day result)

rapid test

(machine based)

3

2-3


39


1)

2)

- - -

3)

4)

5)

6)

7)

8)

9)

10)

2557

40

2

1)

2

2) window period

2 1 seroconversion

3 6

3)

1

2.2

window period window

period 4

2.2.1 HIVviraltesting

p24

antigen

( window period)

18

(qualitative assay)1 NAT (nucleic acid amplification

testing) RNA proviral DNA

1 (positive or negative)


41


p24 antigen

positive

p24 antigen negative

-

-

-

2.2.2

ELISA (enzyme-linked immunosorbent assay)

(agglutination assay) dot line immunoassay

rapid test

ELISA

.. 2551

.. 2552

(sensitivity)

(specificity) 2.1

2557

42

2

2.1

1 p24 antigen 100 99.5

2 100 99.5

3 anti-HIV 99.5 99.0

: .. 2552

2.2.2.1

(predictive value) (positive predictive value: PPV)

(negative predictive value: NPV) PPV NPV

2[2]

.. 2555 0.89

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 %NPV0.05 4.7 83.2 99.8 100.00

0.5 33.3 98.0 99.98 99.997

1.4 58.6 99.3 99.993 99.99

2.0 67.0 99.5 99.995 99.98

5.0 83.97 99.8 99.998 99.97

10.0 91.7 99.9 99.9999 99.94


43


2.2.2.2

3

3

3 2 3

(machine based assay) rapid test

simple test 1 2

3

simple test rapid test

rapid test

2.2.2.3

18

18

3 UNAIDS WHO 2.2

2557

44

2

2.2

18

1 (A1)(1)

2 (A2)(1)

3

(A3)(1)

(anti-HIV negative)

(anti-HIV positive)(2)

(inconclusive)(3,4)

A1+, A2+, A3 _ A1+, A2+, A3+

A1_, A2 _ A1+, A2 _ A1+, A2+

A1+, A2 _ A1+, A2+

A1 A2

A1_ A1+


45


(1) A1, A2 A3 1, 2 3

1

2 3

(2) positive

(newly diagnosed) 2

1

(3) (inconclusive) 2

/ 1 3 A1, A2

A3 3

(4)

2 / 3

(3) NAT neutralization

p24 assay

1) (anti-HIV negative)

(non-reactive)

2) (anti-HIV positive) 3

(reactive)

3) (inconclusive) 3

2 / 1 3

2557

46

2

(false positive) anti-HIV

(false positive)

anti HIV

(antibody cross reactivity)

(mycobacteria) (giardia)

(cytomegalovirus; CMV)

(influenza vaccination)

(human

leukocyte antigen; HLA) 1


47


2.2.2.4

18

18

12 95

12-18

18 12

30 1 50 2

PCP

/

DNA PCR

2 2.3

2557

48

2

DNA PCR

DNA PCR

18

DNA PCR 2

(1) (dried blood spot ; DBS)

EDTA

.

(DBS)

(2) EDTA

citrate 0.5-2.0 mL

-

.

-

12


49


DNA

PCR

1. PCR 1

PCR

2.

PCR ( 4-6

)

4 5

3. PCR 1 PCR

PCR 2 2-4 PCR 2 2

3 4

. 2

2.3

. 2

2 4 PCR

4

2.3

18

2557

50

2

12-18

1.

12-18

.

.

18

5-10

12-18 18

2.

(HIV Ag/Ab)

18

PCR

HIV Ag/Ab 18

24


51


1. (definitive exclusion of HIV infection)

. PCR

2 2

2 4

. 6

2

. PCR 1 4

1 6

CD4

3 18

2. (presumptive exclusion of HIV infection)

. PCR

2

. PCR 1

2

. 6 1

CD4

2557

52

2

2.3

1

8

12

- 1

8

(

5)

(

5)

(

8)

(ant

i - H

IV p

ositiv

e)

(7)

18

(1

)

12

(3)

2

3

(in

conc

lusive

)

(in

conc

lusive

)

2

3

2

3

DNA P

CR

Ant

i - H

IV

1

8

HIV

DNA P

CR

1

(2)

Ant

i H

IV(6)

DNA

PCR

(4)

DNA P

CR

4

(pos

itive

)

(an

ti - H

IV n

egat

ive)

(10)

(9)

2

3

(neg

ative)

(neg

ative)

DNA P

CR

2

(neg

ative)

(pos

itive

)

(neg

ative)

(pos

itive

)


53


(1)

18

DNA PCR

(2) NAT (nucleic acid amplification testing)

(3) 4

VL 50 copies/mL

(4)

(5) 18

(6) 18

DNA

PCR

(7)

3 3 2

(8) PCR 2

24

(9) PCR 2

(10) 6

2557

54

2

5

18

18

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)


55


2.3

2.3.1 CD4(CD4count)

CD4

CD4 CD4

CD4

CD4 2

flow cytometer flow cytometer

flow

cytometer 2.3

CD4

CD4

CD4 1-2 CD4 VL


CD4 3-6

CD4 (absolute CD4)

2557

56

2

(CBC)

CD4

%CD4 x absolute WBC x % lymphocyte CD4 = 10,000

NRBC (nucleated RBC) CD4

%CD4

- CD4

- 5 CD4

EDTA

6

25C

CD4

CD4

steroid

CD4


57


2.3.2 (HIVviralload)

viral load (VL) RNA

real time nucleic amplification

VL

2.3

Viral load

VL

1

1

3 6

1

3 6

VL 2 copies/mL Log10 equivalence

EDTA

6

/

VL

1

VL > 1,000 copies/mL 2.4

VL

2557

58

2

viral load

10

VL

2.3.3(HIVdrugresistancetesting)

genotype

(in-house)

2.3

4

VL

VL > 1,000 copies/mL 2.4

EDTA


59


6

/

2.5

2557

60

2

2.4

(1) VL EDTA 6-9 mL

VL -20 -70C(2) VL drug

resistance

viral load (1)

drug resistance(2)

viral load 1,000 copies/mL

viral load 6 1


61


2.4

CD4 VL

ISO15189

CD4 VL

2.3

CD4 dual platform

(CBC analysis machine)

2.3

(IQC)

(EQA)

HIV testing (machine based)

3

IQC

2 levels

HIV testing (simple test)

3

IQC

2 levels

HIV testing (rapid test)

1

3

IQC

1 level

CD4 test

6

IQC

1 level

Viral load

2

IQC

1 level

Drug resistance testing

2

IQC

1 level

2557

62

2

CD4, viral

load

US FDA

IVD CE mark

(WHO prequalification of diagnostics program)

2556 ( CD4)

2

3

/


63


2.4

Ant

i-HIV

tes

ting

ELIS

A, a

gglutin

atio

n te

st,

dot/lin

e te

st

Clo

tted

bloo

d5

mL

24

.

2-8

C

Ser

um

p

lasm

a1

mL

HIV

vira

l tes

ting(

1)Nuc

leic a

cid

ampl

ificat

ion

test

ing

(NAT

)

EDTA

blo

od2-

3 m

L

24

.

2-8

C

EDTA

plasm

a1

mL

Drie

d bl

ood

spot

1

CD4

coun

tFlow

cyt

omet

ryED

TA b

lood

2-3

mL

6

. (

1

8-25

C

)

(18-

25 C)

Vira

l loa

d te

sting

(HIV

-1 R

NA)

Rea

l tim

e nu

cleic

acid

ampl

ifica

tion

EDTA

blo

od6-

9 m

L

6

.

(

4

C)

6

.

4

-8 C

24

.

EDTA

Plasm

a

2

1.5

mL

PPT

EDTA

gel

(

)

6-9

mL

Gen

otyp

eED

TA b

lood

6-9

mL

6

.

(

4

C)

6

.

4

-8 C

24

.

EDTA

plasm

a

2

1.5

mL

(1)

.,

12

,

2557

64

2

2.5

TruG

ene

Viro

Seq

Sta

nfor

d (in

-hou

se)

(mut

atio

n)

No

evid

ence

of res

ista

nce

Non

eSus

cept

ible

mut

atio

n

Pos

sibl

e re

sist

ance

Pos

sibl

e re

sist

ance

Low

leve

l res

ista

nce

Inte

rmed

iate

res

ista

nce

m

utat

ion

Res

ista

nce

Res

ista

nce

Hig

h leve

l res

ista

nce

(

)


65

3Management of HIV-Infected Adult

3(Management of HIV-Infected Adult)

2

( 50 copies/mL) CD4

(AIDS- related illness)

(adherence)

95

2 12

1 24

2557

66

3

3.1

o CD4 6-12

o

o

o

o

o

o

o


67


CD4

3.1 3.2

2557

68

3

3.1

6

12

-

sexu

al d

ysfu

nctio

n

-

(c

urre

nt li

fest

yle)

6

12


69


EFV

1

1

d

rug

adhe

renc

e

2557

70

3

3.2

C

D4

6

12

- 6

12

CD4

> 35

0 ce

lls/m

m3

VL

1,00

0 co

pies

/mL

6

Pap

sm

ear

1

1

Ana

l PAP

1

1

Ser

um c

rypt

ococ

cal A

g

C

D4

< 10

0 ce

lls/m

m3

2557

72

3

3.2


CD4 350 cells/mm3

CD4 > 500 cells/mm3

VL

2557

CD4

< 500 cells/mm3 3.3

3.3

CD4 CD4 < 500 cells/mm3

CD4 > 500 cells/mm3

adherence


73


CD4 > 500 cells/mm3

3.4

3.4 CD4 > 500 cells/mm3

CD4 > 500 cells/mm3

(Individual benefits)

TB/HIV co-infection

HBV/HIV co-infection with cirrhosis

HCV/HIV co-infection with cirrhosis

HIV-associated nephropathy (HIVAN)

Acute/recent HIV infection

(Public health

benefits)

(Serodiscordant couples)

TB/HIV co-infection

Acute HIV infection

3.3

CD4 < 50 cells/mm3

2

CD4 >50 cells/mm3

2-8

3.5

Cryptococcosis Cryptococcosis

4-6

2557

74

3

Pneumocystis Jiroveci pneumonia (PCP), Mycobacterium Avium Complex (MAC)

2-4

Progressive Multifocal

Leukoencephalopathy (PML)

3.5

CD4 (cells/mm3)

50 > 50

(Tuberculosis) 2 *

2 2-8

Cryptococcosis 4-6

PCP/MAC/ 2-4

CMV/PML/Cryptosporidium

:

2


75


3.4

3.6

NRTIs + NNRTI TDF + 3TC TDF/FTC

EFV

3.6

NRTI backbone

+

NNRTIs

NNRTIs

TDF/FTCEFV LPV/r

TDF + 3TC*

ABC + 3TC

AZT + 3TC

RPV

NVP

ATV/r

*

TDF NRTIs ABC + 3TC AZT

+ 3TC ABC

VL < 100,000 copies/mL

EFV

NNRTIs RPV NVP

RPV VL VL

> 100,000 copies/mL

NNRTIs 3

PIs LPV/r ATV/r

2557

76

3

d4T

d4T

VL < 50 copies/mL

integrase inhibitors

3 RAL

DRV/r

2

ABC ABC

(hypersensitivity reaction)

HLA-B*5701 HLA-B*5701

ABC

HLA-B*5701

ABC 6

2 (1) (2) (3)

(4)

creatine

phosphokinase lymphopenia

ABC Child-Pugh Score of 7-12


77


3.5

3.5.1

3 (1) virological failure

(2) immunological failure (3) clinical failure

1 2

3

virological failure

: virological failure HIV RNA (VL)

200 copies/mL 6

3.7 virological failure

virological failure

1.

adherence

VL

1 VL

2.

VL

VL

> 50-1,000

copies/mL

-

- 2-3

VL

>1,000

copies/mL

HIV drug resistance

genotypic testing

adherence

3

1 VL

VL > 10

VL

3 VL

< 50 copies/mL

VL 10

adherence

VL > 1,000

copies/mL

2557

78

3

(1) NNRTI VL

1,000 copies/mL

(2) boosted-PIs

poor adherence

VL 50 copies/mL

- VL > 1,000 copies/mL

-

- 2-6

4

3.8 3.9

3.5.2

(Multi-class antiretroviral treatment failure)

VL < 50 copies/mL

3

3 2

VL 3


79


3.8

1.

2. 3

integrase inhibitor, entry inhibitor

3.

1) Integrase inhibitors: RAL, DTG

2) Protease inhibitors: DRV ()

3) NNRTIs: ETR, RPV ()

4) CCR5 inhibitors: MVC

3.9

NRTI NRTI

TDF

AZT/3TC

LPV/r

ATV/r

DRV/r, RAL*, DTG

AZT, d4T ABC

TDF/FTC

TDF/3TC

* RAL NRTI backbone

: EVG/COBI

creatinine clearance

70 mL/min

2557

80

3

3.6

12

TDF, 3TC EFV 3.10

TDF VL < 50 copies/mL HBV

(HBsAg) EFV

1-2

()

1

12


81


3.10

EFV EFV

NVP NVP 400 mg 24 .

OD

1

LPV/r LPV/r 2 12 . 4 24 .

ATV/r

TDF TDF

AZT d4T TDF 24 .

VL < 50 copies/mL TDF

3TC 3TC 1 12 . 2 24 .

2557

82

3

3.7

1 NRTI + 1 NNRTI 1 NRTI + 1 PI boosted RTV 1 NRTI + RAL

2 NRTIs

NRTIs 2

d4T + AZT antagonism

FTC + 3TC resistance profiles

TDF + ddI ddI

d4T + ddI peripheral neuropathy, pancreatitis,

hyperlactatemia lactic acidosis

2

Triple NRTI combinations TDF + 3TC + ABC

NVP CD4 > 400 cells/mm3 CD4

> 250 cells/mm3

2 NNRTIs combination

ATV + IDV hyperbilirubinemia

VL < 50 copies/mL


83


3.8 (Drug-druginteraction)

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

2557

84

3

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

6 1) Ergotism

- (peripheral vascular vasoconstriction)

Ergot derivative ergotamine

(ischemia)

- Ergot CYP450 CYP inhibitor

Ergot clarithromycin, ketoconazole,

NNRTIs EFV PIs RTV

- PIs EFV ergotamine

: /

() (cyanosis)

(gangrene)

: (vasodilator drug)

prostaglandin analogue


85


2) Torsades de Pointes

- (ventricular arrhythmia)

QT prolong

- PIs ATV QT

prolong

: CYP inhibitor RTV

QT prolong terfenadine, astemizole,

cisapride pimozide calcium channel bolckers diltiazem

flecainide, propafenone, amiodarone,

quinidine

3) Rhabdomyolysis

-

CYP inhibitor RTV

statins simvastatin

pravastatin rosuvastatin

- fibrate statins

- 2 statins

pravastatin rosuvastatin fibrate derivative

fenofibrate gemfibrozil

2557

86

3

4) Symptomatic hypotension

-

- CYP inhibitor RTV

dihydropyridine calcium channel blockers felodipine, nifedipine,

amlodipine -blocker

sidenafil (viagra)

- sidenafil boosted PIs LPV/r

sidenafil 11

o 25 mg 48 .

o sidenafil nitrate

5) Excessive sedative

- benzodiazepines

- benzodiazepines midazolam, triazolam, alprazolam

diazepam benzodiazepines

- lorazepam CYP450

6) Cushings syndrome

Cushings syndrome

(adrenal insufficiency) RTV fluticasone

RTV CYP inhibitor

CYP450


87


3.1

1

e

rgot

amin

e

Ergo

tam

ine

grou

p

(dih

ydro

ergo

tam

ine,

ergo

tam

ine)

met

herg

in

(met

hylerg

onov

ine)

PIs, EF

V

E

rgot

boo

sted

PIs

E

rgot

PI

E

FV

seve

re v

asoc

onst

rictio

n

gan

gren

e

EVG

/CO

BI

EVG

CO

BI

E

rgot

E

rgot

EVG

/CO

BI

H 2-rec

epto

r

anta

gonist

s (H

RAs)

ATV

HRAs

ATV

b

oost

ed A

TV

/

HRAs

1

0

.

RPV

HRAs

RPV

H

RAs

12

.

4

.

R

PV

Pro

ton-

pum

p

inhibi

tors

(PPIs)

ATV

PPIs

ATV

ATV

PIs

,

P

Is

P

PIs

1

2

.

A

TV

bo

oste

d AT

V

RPV

PPIs

RPV

RPV

Cisap

ride

EVG

/CO

BI/T

DF/

FTC

c

isap

ride

s

erio

us life

-thr

eate

ning

eve

nts

EFV

Ant

ifung

als

Fluc

onaz

ole

EFV

-

ETR

ETR

NVP

NVP

AUC

110

%

NVP

2557

88

3

Itrac

onaz

ole

EFV

Itrac

onaz

ole

OH-it

raco

nazo

le A

UC,

Cm

ax

C

min

35-

44%

itrac

onaz

ole

itrac

onaz

ole

ETR

Itrac

onaz

ole

ET

R

itrac

onaz

ole

itrac

onaz

ole

NVP

Itrac

onaz

ole

NVP

itrac

onaz

ole

NVP

Ket

ocon

azol

eEF

VKet

ocon

azol

e

-

ETR

Ket

ocon

azol

e

ET

R

keto

cona

zole

NVP

Ket

ocon

azol

e AUC

72%

NVP

1

5-30

%

Pos

acon

azol

eEF

VPos

acon

azol

e: A

UC

50%

ETR

ETR

Voric

onaz

ole

EFV

Voric

onaz

ole:

AUC

77%

EFV:

AUC

44%

vor

icon

azol

e 40

0 m

g

12

.

EFV

300

mg

24

.

ETR

Voric

onaz

ole

ET

R

vor

icon

azole

voric

onaz

ole

NVP

Voric

onaz

ole

NVP

voric

onaz

ole


89


(an

ticon

vuls

ants

)

Car

bam

azep

ine,

phen

obar

bita

l,

phen

ytoi

n

EFV

Car

bam

azep

ine

+ EF

V:

Car

bam

azep

ine

AUC

27%

EFV

AUC

36%

Phe

nyto

in +

EFV

: EF

V

phen

ytoi

n

EFV

ETR

Ant

icon

vulsan

t

ETR

NVP

Ant

icon

vulsan

t

NVP

NVP

Ant

imyc

obac

teria

ls

Clarit

hrom

ycin (C

lar)

EFV

Clar AUC

39%

azith

rom

ycin

(

MAC)

ETR

Clar AUC

39%

OH-c

lar AUC

21%

ETR A

UC

42%

a

zith

rom

ycin

(

MAC)

NVP

Clar AUC

31%

OH-C

lar AUC

42%

azith

rom

ycin

(

MAC)

ATV/

rClar AUC

94%

Q

T pr

olon

g

clar

ithro

myc

in 5

0%

azith

rom

ycin

2557

90

3

DRV/

r, LP

V/r

Clar AUC

5

7%

clar

ithro

myc

in

azith

rom

ycin

- CrC

l 30-

60 m

L/m

in

clar

ithro

myc

in 5

0%

- CrC

l < 3

0 m

L/m

in

clar

ithro

myc

in 7

5%

Rifa

butin

EFV

Rifa

butin

3

8%Rifa

butin

450

-600

mg/

day

EFV

P

Is

ETR

Rifa

butin

met

abol

ite A

UC

17%

ETR A

UC

37%

Rifa

butin

300

mg/

day

ETR

b

oost

ed P

Is

b

oost

ed P

Is

rifa

butin

NVP

Rifa

butin

AUC

17%

met

abol

ite

AUC

24%

, NVP

Cm

in

16%

rifab

utin

Rifa

mpi

cin

EFV

EFV

AUC

26%

E

FV 6

00 m

g/da

y

>60

kg

E

FV 8

00

mg/

day

ETR

ETR

NVP

NVP

2

0-58

%

NVP

400

mg/

day

lead

-in

E

FV

EVG

/CO

BI/T

DF/

FTC

Rifa

mpi

cin

EVG

CO

BI

RAL

RAL

400

mg:

RAL

AUC

40%

, C

min

61%

RAL

400

mg

12

.,

rifam

picin

RAL

800

mg

12

.

RAL

AUC

27%

, C

min

53%

RAL

800

mg

12

.

rifab

utin


91


Ben

zodi

azep

ines

Alp

razo

lam

ETR

alpr

azol

am

PIs

PIs

benz

odiaze

pine

Diaze

pam

ETR

d

iaze

pam

d

iaze

pam

PIs

PIs

benz

odiaze

pine

Lora

zepa

mEF

VLo

raze

pam

: C

max

16%

,

AUC

Mid

azol

amPIs

E

FV

mid

azol

am

Triazo

lam

PIs

E

FV

triaz

olam

Ant

idep

ress

ants

Ser

tralin

eDRV/

r, EF

V

s

ertra

line

sertr

aline

Traz

odon

ePIs

tra

zodo

ne

tra

zodo

ne

Tricyc

lic

antid

epre

ssan

ts (T

CAs

)

PIs

T

CAs

T

CAs

(al

pha-

adre

nerg

ic b

lock

ers

5-al

pha-

redu

ctas

e in

hibi

tors

)

Tam

sulo

sin

PIs

tam

sulo

sin

tam

sulo

sin

d

ose

Fina

ster

ide

PIs

fi

nast

erid

e

finas

terid

e

2557

92

3

Am

ioda

rone

PIs

a

mio

daro

ne

Diltiaze

mPIs

d

iltiaze

m

diltiaze

m

50

%

ATV

R

TV

EFV

d

iltiaze

m A

UC

69%

diltiaz

em

NVP

Diltiaze

m

diltiaz

em

Dihyd

ropy

ridine

calcium

chan

nel b

lock

ers (D

CCBs

)

EFV,

NVP

DCCBs

C

CBs

PIs

D

CCBs

D

CCBs

pu

lmon

ary

arte

rial h

yper

tent

ion

Bos

enta

nPIs

b

osen

tan

b

osen

tan

unbo

oste

d AT

V

PI (

u

nboo

sted

ATV

)

> 1

0

b

osen

tan

62.5

mg

PI (

u

nboo

sted

ATV

)

bos

enta

n

b

osen

tan

36

.

P

I

PI

1

0

62.

5 m

g

Sild

enafi

lPIs

s

ilden

afil

P

Is

ETR

s

ilden

afil

E

TR


93


(co

rtic

oste

roid

s)

Dex

amet

haso

nePIs, NVP

, EF

V, E

TR,

RPV

Dex

amet

haso

ne

P

Is, N

VP, E

FV,

ETR, RPV

R

PV,

dex

amet

haso

ne

Flut

icas

one, b

udes

onide

(inha

led

intra

nasa

l)

RTV

bo

oste

d

PIs

flutic

ason

e

bu

deso

nide

Her

bal p

rodu

cts

St.J

ohn

s W

ort

EFV,

ETR

, NVP

NNRTI

s

Hor

mon

al c

ontrac

eptiv

es

Ethiny

l est

radi

ol (E

E),

prog

estin

,

norg

estim

ate,

nore

thindr

one

ETR

EE A

UC

22%

Nor

ethind

rone

NVP

EE A

UC

20%

Nor

ethind

rone

AUC

19%

Dep

ot m

edro

xypr

oges

tero

ne a

ceta

te

EFV

EE

A

UC, levo

noge

stre

l

AUC

83%

, no

relg

estro

min

AUC

64%

,

et

onog

estre

l (im

plan

t)

le

vono

gest

rel, no

relg

estro

min, e

tono

gest

rel

2557

94

3

RPV

EE

14%

nore

thindr

one:

no

sign

ifica

nt e

ffect

IDV

EE A

UC

25%

nore

thindr

one

AUC

26%

NFV

EE A

UC

47%

nore

thindr

one

AUC

18%

ATV/

rEE

prog

estin

, no

rges

timat

e

E

E

3

5 g

p

roge

stin

norg

estim

ate

nor

ethind

rone

DRV/

rEE

AUC

44%

nore

thindr

one

AUC

14%

LPV/

rEE

4

2%

nore

thindr

one

AUC

17%

HM

G-C

oA red

ucta

se in

hibi

tors

Ato

rvas

tatin

EFV,

ETR

, NVP

Ato

rvas

tatin

AUC

32-

43%

E

FV, ET

R

ato

rvas

tatin

Fluv

asta

tinET

RFluv

asta

tin

fluva

stat

in


95


Lova

stat

in, s

imva

stat

inEF

VSim

vast

atin A

UC

68%

sim

vast

atin

ETR

Lova

stat

in

Sim

vast

atin

sim

vast

atin

lo

vast

atin

NVP

Lova

stat

in

Sim

vast

atin

sim

vast

atin

lo

vast

atin

Pra

vast

atin,

rosu

vast

atin

EFV

Pra

vast

atin A

UC

44%

Ros

uvas

tatin

pra

vast

atin

ro

suva

stat

in

ETR

Ora

l an

ticoa

gula

nt

War

farin

EFV,

NVP

War

farin

INR

war

farin

ETR

War

farin

INR

war

farin

Clo

pido

grel

ETR

c

lopi

dogr

el

2557

96

3

Opi

oid

anta

goni

st

Met

hado

neBoo

sted

PIs

R

-met

hado

ne (ac

tive

form

met

hado

ne)

LPV/

r

m

etha

done

26-

53%

ATV/

r, DRV/

r

m

etha

done

(

m

etha

done

16-

18%

)

met

hado

ne w

ithdr

awal

met

hado

ne

EFV,

NVP

m

etha

done

41

-52%

m

etha

done

with

draw

al

met

hado

ne

ETR

AZT

AZT

2

9-43

%

AZT

:

AUC =

ae

ra u

nder

the

cur

ve

C

max =

max

imum

plasm

a co

ncen

tratio

n

C

min

= m

inim

um p

lasm

a co

ncen

tratio

n

CrC

l =

crea

tinine

clea

ranc

e


97


3.1

2

N

NRTI

s, R

AL,

and

PIs

EFV

ETR

NVP

RAL

ATV

Unb

oost

ed A

TV:

ATV

AUC

74%

EFV

Unb

oost

ed A

TV:

ETR A

UC

50%

Cm

in

58%

ATV

AUC

17%

Cm

in

47%

-Unb

oost

ed A

TV:

RAL

AUC

72%

Boo

sted

ATV

:

A

TV

unbo

oste

d AT

V

EFV

Boo

sted

ATV

:

ETR A

UC

C

min

~ 3

0%

ATV

AUC

14%

Cm

in

38%

Boo

sted

ATV

:

ATV

AUC

42%

Cm

in

72%

NVP

AUC

25%

Boo

sted

ATV

:

RAL

AUC

41%

A

TV

E

FV

RTV

E

TR

A

TV

ATV/

r

N

VP

A

TV

ATV/

r

DRV

Boo

sted

DRV:

DRV

AUC

13%

, Cm

in

31%

EFV

AUC

21%

Boo

sted

DRV:

DRV

ETR A

UC

37%

, Cm

in

49%

Boo

sted

DRV:

DRV

AUC

24%

NVP

AUC

27%

Cm

in

47%

Boo

sted

DRV:

RAL

AUC

29%

Cm

in

38%

D

RV/

r

600/

100

mg

12

. +

EFV

600

mg

24

.

D

RV/

r

600/

100

mg

+ ET

R 1

00 m

g

12

.

D

RV/

r

600/

100

mg

+ NVP

200

mg

12

.

D

RV/

r

600/

100

mg

+ RAL

400

mg

12

.

2557

98

3

EFV

ETR

NVP

RAL

EFV

-ET

R

NVP

EFV

AUC

22%

EFV

AUC

36%

-

ETR

ETR

-ET

R

ETR C

min

17%

RAL

Cm

in

34%

-

IDV

IDV

3

1%ID

V

IDV

3

1%

NVP

IDV/

r 80

0/10

0 m

g

12

.

+ EF

V 60

0 m

g

24

.

IDV/

r 80

0/10

0 m

g +

NVP

200

mg

12

.

LPV/

r

LPV/

r 50

0/12

5 m

g

12

.

+ E

FV 6

00 m

g:

LPV

L

PV/

r 40

0/10

0 m

g

12

.

EFV

ETR

30-

45%

LPV

1

3-20

%

LPV

AUC

27%

Cm

in

51%

LPV/

r 50

0/12

5 m

g

12

.

+ EF

V 60

0 m

g

24

.

LP

V/r 50

0/12

5 m

g +

NVP

200

mg

12

.


99


EFV

ETR

NVP

RAL

NVP

NVP

EFV

AUC

22%

ETR

-

-

RAL

RAL

AUC

36%

ETR C

min

17%

RAL

Cm

in

34%

-

-

SQ

V

SQ

V 1,

200

mg

8

.:

SQ

V AUC

62%

EFV

AUC

12%

SQV/

r 1,0

00/1

00 m

g

12

.:

SQ

V AUC

ETR A

UC

33%

, Cm

in

29%

SQ

V 60

0 m

g

8

.:

SQ

V AUC

24%

NVP

SQV/

r 1,0

00/1

00 m

g

12

.

SQV/

r 1,0

00/1

00 m

g

12

.

*

LPV

7

.3 m

g/L

(L

PV

1-4

mg/

L)

2557

100

3

3.9

3.9.1

1) (hepatitis B)

9

( 6-14)

4 (liver enzymes

> 10 upper limit)

3

anti-HBc, anti-HBs HBsAg

HBsAg

2) (hepatitis C)

8

( 72-95) ( 1-12)

( 9-27)

95

( 500,000 IU/mL)


101


2

anti HCV CD4 > 200 cells/mm3

( CD4 )

3)

herpes simplex type 2

2

(atypical manifestation)

nuerosyphilis

(trichomonas

vaginalis) genital tract

2557

102

3

RPR

1 MSM,

( 2-4

) RPR titer >1:32 CSF RPR

neurosyphilis

-

2 neurosyphilis

3.9.2(OIs6)

1)

latent infection

primary tuberculosis 10

50

5-10

6

CXR

CXR


103


2) CMV retinitis

cytomegalovirus (CMV)

CD4 < 100 cells/mm3

(sensitivity 7%)

indirect ophthalmoscope CD4

< 100 cells/mm3

3)

CD4 < 100 cells/mm3

CD4 < 100 cells/mm3

serum cryptococcal Ag CD4 < 100

cells/mm3 3.1 Crypto Ag positive

LP meningitis ( stiff neck + ve)

cryptococcus menigitis

( )

LP cryptococcemia

fluconazole LP cryptomeningitis

2557

104

3

/ cryptococcus

menigitis CSF cryptococcal antigen

serum cryptococcal Ag

cryptomeningitis ( serum antigen

meningitis disseminated disease serum

antigen CSF ) secondary prophylaxis

fluconazole 200 mg CD4 > 100 cells/mm3 3

serum cryptococcal Ag

primary prophylaxis


105


3.1 Crypto Ag

* primary prophylaxis

primary prophylaxis

** CT brain lumbar puncture

Anti HIV +CD4 < 100 cells/mm3

serum cryptococcalantigen

uconazole 800 mg 2

400 mg 8 CSF WBC, sugar ,

cryptococcal Ag +

2

amphotericin B 0.7-1 mg/kg/day+ uconazole 800 mg 2

uconazole 400-800 mg 8-10

10 uconazole 200-400 mg

1 CD4 > 100

cells/mm3 3

4-6 ***

+ *

Negative

lumbarpuncture**

Positive

2557

106

3

:

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

3.9.3

70

HIV

dementia, impaired cognitive function

2

MSM transgender (TG)


107


Q2 Q9

Q2 Q9

3.9.4

BMI (kg/m2)

17 BMI 18.5 2

PIs

6

2557

108

3

3.9.5

1)

20 HPV

CD4

CD4

pap smear 6

1

2)

11-36 human papilloma virus

anal dysplasia

HPV

CD4

Pap smear 6


109


controversial standard protocol

MSM digital

anorectal examination anal pap 1-3

anoscopy

3)

3.10

VL CD4 VL

CD4

VL

50 copies/mL 6 VL 50 copies/mL

200 copies/mL

50-200 copies/mL

VL

CD4 CD4

clinical failure

2557

110

3

VL 6

1

2-4 VL

.

CD4

CD4

CD4

(OI prophylaxis)

CD4 6

CD4

100-150 cells/

CD4

CD4 CD4 25 50

CD4 VL < 50 copies/mL

3.11

2 NRTIs

AZT ddI NNRTIs PIs

(creatinine

clearance; CrCl) Child-Pugh score

3.13 3.14


111


3.1

3

eGFR

CrC

l (m

L/m

in)(1

)

Hem

odia

lysi

s

50

30-4

910

-29

< 10

NRTI

s

3TC

300

mg

24

.

1

50 m

g

12

.

150

mg

24

.

100

mg

24

.(2

)50

-25

mg

24

.(2

)50

-25

mg

24

.(2

) AD

(3)

TDF(

4)30

0 m

g

24

.

300

mg

48

.

300

mg

2

300

mg

7

AD

(3)

AZT

200-

300

mg

12

.

10

0 m

g

8

.

300

mg

24

.

d4T

30 m

g

12

.

30 m

g

12

.

15 m

g

12

.

15 m

g

24

.

15 m

g

24

.

15 m

g

24

. AD

(3)

ddI(5

)>

60 k

g40

0 m

g

24

.

200

mg

24

.

150

mg

24

.

100

mg/

24

.

< 60

kg

250

mg

24

.

125

mg

24

.

100

mg

24

.

75 m

g/24

.

ABC

300

mg

12

.

6

00 m

g

24

.

TDF/

FTC

1

24

.

48

.

2557

112

3

eGFR

CrC

l (m

L/m

in)(1

)

Hem

odia

lysi

s

50

30-4

910

-29

< 10

NNRTI

s

EFV

600

mg

24

.

NVP

200

mg

12

.

ETR

200

mg

12

.

RPV

25 m

g

24

.

EFV/

TDF/

FTC

1

24

.

RPV/

TDF/

FTC

1

24

.

Pro

teas

e in

hibi

tor (P

Is)

ATV

400

mg

24

.

300/

100

mg

24

.

Hem

odia

lysi

s (H

D)

: AT

V/r 30

0/10

0 m

g

24

.

AT

V

ATV

/r

DRV

800/

100

mg

24

. (n

ave

)

600/

100

mg

12

.

LPV/

r40

0/10

0 m

g

12

.

HD

Inte

gras

e in

hibi

tors

RAL

400

mg

12

.

EVG

/CO

BI/

TDF/

FTC

1

24

.

C

rCl 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:

3.12

3

1) (life-threatening adverse effects)

2) (serious adverse effects)

3) (long-term adverse effects)

3.15

2557

116

3

3.1

5

/

1)

(lif

e-th

reat

enin

g ad

vers

e eff

ects

)

Steve

ns-Jo

hnso

nSyn

drom

e (S

JS)

Toxic

Epide

rmal N

ecroly

sis

(TEN)

NVP 0

.3-1

%,

DLV

EFV

0.1

%, E

TR

< 0.

1%

1

-2

A

ZT, dd

I, ABC,

IDV,

LPV/

r, AT

V, D

RV

2

-3

2

-3

s

kin

erup

tion

muc

osal u

lcer

atio

n

(

)

b

liste

r/bu

llae

epid

erm

al d

etac

hmen

t

necr

osis

fluid

dep

letio

n, b

acte

ria

or fu

ngal sup

erinfe

ction,

multio

rgan

failure

N

VP

NVP

CD4 >

250 ce

lls/m

m3

NVP

200

mg

24

.

2

200

mg

12

.

c

otrim

oxaz

ole

su

ppor

tive,

,

,

pare

nter

al n

utrit

ion

s

uper

infe

ctio

n

c

ortic

oste

roid

s

IVIG

cros

s re

actio

n

N

NRTI

s


117


/

N

VP

hepa

tic ne

crosis

N

VP

4%

11%

C

D4

> 25

0 ce

lls/m

m3

(

0.9

%

C

D4 250

cells

/mm

3 )

6

.3%

C

D4

> 4

00

cells

/mm

3 (

2.3%

C

D4

400

cells

/mm

3 )

1-3

1

8

fulm

inan

t

hepa

tic fa

ilure

ence

phalop

athy

50%

DRES

S sy

ndro

me

CD4

(> 2

50 c

ells/m

m3

, >

400

cells/m

m3

)

Bas

elin

e AST

ALT

H

BV

/

HCV

NVP

CD4

> 25

0 ce

lls/m

m3

C

D4

> 40

0

cells

/mm

3

NVP

2

AST

ALT

2

N

VP

supp

ortiv

e ca

re

N

VP

N

NRTI

s

E

FV

NVP

3T

C

FTC

T

DF

2557

118

3

/

Lacti

c acid

osis,

hepa

tic

steato

sis +

/- pa

ncrea

titis

(seve

re mi

tocho

ndria

ltox

icities

)

N

RTI

s

d

4T

d

dI

AZT

0.85

%

50%

non

spec

ific

gastro

inte

stinal syn

drom

e

NRTI

d

4T

ddI,

AZT

BM

I

d4T

d

dI

ddI

hydr

oxyu

rea

ribav

irin

d

4T

ddI

lact

ate

su

ppor

tive

care

IV fl

uid

ac

idos

is

IV b

icar

bona

te,

hem

odialysis/

hem

ofiltr

atio

n,

IV th

iam

ine

/

rib

oflav

in

lact

ate

seru

m lac

tate

:

La

ctat

e

(

> 5

mm

ol/L

)

Arte

rial p

H

(

40

0

cells

/mm

3

NVP

AST,

ALT

2

4

1

3

3-6

AST,

ALT

3-4

h

epat

otox

icity

HBV

3

TC, F

TC, T

DF

AST,

ALT

ALT

> 5

-10

AST,

ALT


123


/

Neph

rolith

iasis,

urolith

iasis,

crysta

lluria

ID

V

12.4

% (4

.7-3

4.4%

)

ATV,

EFV

/

p

yuria

, he

mat

uria, cr

ysta

lluria

crea

tinine

neph

rolithias

is

p

eak

IDV

IDV

1.5-

2

ur

inalys

is

seru

m c

reat

inine

3-6

IV

fluid

IDV

Neph

rotox

icity

ID

V , TD

F

ATV

IDV

TDF

n

ephr

ogen

ic d

iabe

tes insipi

dus

F

anco

ni s

yndr

ome

:

ID

V: C

r

, p

yrur

ia, h

ydro

neph

rosis

ren

al a

troph

y

TD

F: C

r

, p

rote

inur

ia, g

lyco

suria

,

hypo

kalem

ia, hy

poph

osph

atem

ia,

non-

anio

n ga

p, m

etab

olic a

cido

sis

C

D4

IDV

ser

um cre

atinine,

urinalys

is, se

rum

pota

ssium

phos

phor

us

supp

ortiv

e ca

re

elect

rolyte

s

2557

124

3

/

Panc

reatitis

ddI

1

-7%

d

dI

d4T

rib

avirin

hydr

oxyu

rea

3

TC, d

4T

TDF

Am

ylas

e

lip

ase

in

trace

llular

/

ser

um d

dI

panc

reat

itis

hype

rtrig

lyce

ridem

ia

ddI

d

4T,

hydr

oxyu

rea,

rib

avirin

ddI

T

DF

d

dI

ddI

panc

reat

itis

ddI

d4T,

rib

avirin,

hydr

oxyu

rea

ddI

TDF

am

ylase

lipas

e

hype

rtrig

lyce

ridem

ia

panc

reat

itis

bow

el re

st, I

V hy

drat

ion,

pain c

ontro

l, pa

rent

eral

nutri

tion

Bleed

ing ep

isode

sinc

rease

in he

moph

iliac

patie

nts

PIs

2-3

PIs

hem

ophilia

NN

RTI

regi

men

F

acto

r VIII


125


/

3)

(lo

ng-ter

m a

dver

se e

ffec

ts)

Lipod

ystrop

hy

Lipo

hype

rtrop

hy

PI

NNRTI

-bas

ed re

gim

ens

d

4T

A

ZT

Lipo

atro

phy

N

RTI

s

d

4T

A

ZT,

ddI

TD

F,

ABC

Lip

ohyp

ert

rophy

(do

rsoc

ervica

l

fat

pad

buff

alo

hum

p)

Lipo

atro

phy

b

aseline

BM

I

lipoa

trop

hy

inject

able p

oly-

L-lact

ic

acid

lipoh

yper

troph

y

rest

orat

ive

L

PV/

r

A

TV/r

visc

eral

fat

lip

ohyp

ertro

phy

reco

mbina

nt h

uman

grow

th h

orm

one

GH-relea

sing

hor

mon

e

analog

ue

Hype

rlipide

mia

P

Is

(

unbo

oste

d AT

V)

4

7-

75%

NRTI

s

NNRTI

s

- PIs >

NNRTI

s

- EF

V >

NVP

- d4

T >

AZT

> A

BC >

TDF

PIs

L

DL,

TC

TG

HDL

ATV

,

DRV,

LPV,

SQ

V

boos

ting

RTV

d4

T

TG, L

DL

TC

EF

V, N

VP

L

DL,

TC,

TG

H

DL

E

FV

NVP

- PIs: R

TV-b

oost

ed P

Is

ATV

/r

LD

L,

TG

PIs

N

NRTI

s

d4T

fa

sting

lipid

pro

file

3

-6

c

ardia

c ris

k

fact

ors

lifes

tyle

mod

ifica

tions

sim

vast

atin

ator

vast

atin

rhab

dom

yolysis

2557

126

3

/

Insulin

resis

tance

/diab

etes

mellitu

s

d4T,

AZT

PIs

3

-5%

p

olyu

ria,

polydi

psia,

polyph

agia, fa

tigue

hy

perg

lyce

mia

FB

S

1-3

3-6

d

4T, AZT

N

NRTI

s

m

etfo

rmin

,

glita

zone

s, s

ulfo

nylure

a

insu

lin

Perip

heral

neuro

pathy

ddI

1

2-34

%, d4

T

52%

mon

othe

rapy

neur

opat

hy

p

ainf

ul n

euro

path

y

p

erip

hera

l

neur

opat

hy

a

dva

nced

HIV

dise

ase

d4T

d

dI

intra

cellu

lar ac

tivities

ddI

TDF,

hyd

roxy

urea

,

ribav

irin

g

abap

entin

, tric

yclic

antid

epre

ssan

ts,

lam

otrig

ine,

oxyc

arba

maz

epine,

topi

ram

ate,

tra

mad

ol,

narc

otic a

nalg

esics,

caps

aicin

crea

m, t

opical

lidoc

aine


127


/

Osteo

necro

sis

ol

d PIs

H

IV

s

ympt

omat

ic

osteon

ecro

sis 0.08-

1.33

%

a

sym

ptom

atic

oste

onec

rosis

4%

MRI

peria

rticu

lar pa

in

85

%

fe

mor

al h

ead

Adv

ance

d AID

S

ste

roid

s

hyp

erlip

idem

ia

ste

roid

15%

bo

ne h

ead

MRI

3-

6

1

6

1

Con

serv

ative

man

agem

ent:

Sur

gica

l int

erve

ntio

n:

- Ea

rly s

tage

s

c

ore

deco

mpr

ession

/

bone

gra

fting

- Sev

ere

debi

litat

ing

dise

ase

tot

al joi

nt

arth

ropl

asty

Car

diov

ascu

lar eff

ects

,

includ

ing m

yoca

rdial

infarc

tion (

MI),

cereb

rovas

cular

accid

ents

(CVA

)

PIs

M

I

CVA

ABC

M

I

dd

I M

I

obse

rvat

iona

l stu

dies

RCT

M

I 0

.3-0

.6%

CVA

0

.1%

co

rona

ry

arte

ry d

isea

se

c

er-

ebro

vasc

ular

acc

iden

ts

C

VD

c

oron

ary ar

tery

dise

ase

p

rem

atur

e

coro

nary

arte

ry d

isea

se

c

ardi

ac risk

fact

ors

hype

rlipi

dem

ia

hype

rglyce

mia

life

style

mod

ificat

ion

hype

rlipi

dem

ia, hy

perte

nsio

n, in

sulin

res

ista

nce/

diab

etes

mellitus

c

ardi

ac risk

fact

ors

lifes

tyle m

odifica

tions

card

iova

scular

effe

cts

NNRTI

s

ATV-

base

d re

gim

en

d4T

2557

128

3

3.12.1 ()

PIs 1.7-2.3

National Cholesterol Education Program,

Adult Treatment Panel III (NCEP ATP III)

10 Framingham

LDL 3.2

10 20

LDL-C 80 mg/

dL

(lifestyle modification)

LDL 220 mg/dL

primary secondary coronary prevention statin

LDL 3.2

LDL


129


3.2

1

0

1

HbA1

C < 6

.5-7.0

%

10

20%

2

SBP

< 130

mmH

gSB

P < 1

40 m

mHg

DBP

< 80 m

mHg

DBP

< 90 m

mHg

SBP >

140

mm

Hg

DBP >

90

mm

Hg

3

(mg/d

L)

4

< 15

5< 1

90LD

L< 8

0< 1

15

2

10

20%

2557

130

3

:

1. 10

10 Framingham www.cphiv.dk/tools.aspx

2.

. PI/r NNRTIs, RAL PI/r

. d4T AZT, TDF ABC

3.

LDL 400

mg/dL LDL [ LDL = TC - HDL - (TG/5)]

LDL 30 mg/dL (Ref)

4.

500 mg/dL

3.16

PI

NNRTI

Statin Atorvastatin 10-80 mg/day

1

( 40 mg/day)

2

Fluvastatin 20-80 mg/day 2 2

Pravastatin 20-80 mg/day 2,3 2

Rosuvastatin 5-40 mg/day 1

( 20 mg/day)

1

Simvastatin 10-40 mg/day 2

Cholesterol

uptake

Ezetimide 10 mg/day

:

1. statin statin

2. statin statin statin

3. DRV/r pravastatin


131


3.13 (Adherencetoantiretroviraltherapy)

3.13.1 adherence

1)

2)

3)

adherence

4) adherence

5)

()

6)

7) adherence

8) non-adherence non-adherence

non-adherence

2557

132

3

3.13.2adherence

adherence 2

3.17 3.18

adherence

adherence 1

adherence

adherence visual

analogue scale, self report,

adherence

adherence

30

% adherence

% adherence =

dose

dose


133


adherence

adherence

adherence

1

adherence

adherence (

)

2

adherence

fixed dose combination adherence

adherence

adherence

adherence

2557

134

3

3.1

7

a

dher

ence

/

1.

(V

L as

say)

g

old

stan

dard

adhe

renc

e

VL

V

L

a

dher

ence

ad

here

nce

V

L

(und

etec

tabl

e leve

l)

2.

(ther

apeu

tic d

rug

mon

itorin

g)

/

a

dher

ence

12

3.

(DO

T)

adhe

renc

e


135


3.1

8

a

dher

ence

/

1.

(self re

port)

2.

(pill

coun

ts)

a

dher

ence

(p

ill du

mpi

ng)

7

7

p

ill du

mpi

ng

3.

(pill

taking

rec

ord)

/

4.

(p

harm

acy

refil

l

reco

rds)

a

dher

ence

(p

ill du

mpi

ng)

2557

136

3

5.

(e

lect

ronic

drug

mon

itorin

g)

M

EMS

(med

icat

ion

even

ts m

onito

ring

syst

em) c

aps

6.

(follo

w u

p ap

pointm

ent)

7. V

isua

l ana

logu

e sc

ale

self r

epor

t

8.

(pro

vide

r es

timat

ion)

a

dher

ence


137


3.14 Immunereconstitutioninflammatorysyndrome(IRIS)

IRIS

3.19 Immune reconstitution

inflammatory syndrome IRIS

Definition

IRIS

IRIS 2

Unmasking IRIS

3-6

Paradoxical IRIS

mycobacterium (TB MAC) cryptococcus 3-6


o

o CD4

IRIS (Graves

disease)

2557

138

3

IRIS

-

IRIS IRIS

paradoxical IRIS

NSAIDs short course corticosteroids

IRIS

o

o

systemic corticosteroids

3.20 IRIS

Tuberculosis paradoxical reaction [ (

38.5oC), , ,

cutaneous lesions, ascites, CXR worsening], tuberculoma,

inflammatory bowel perforation, serositis, psoas abscess

MAC

atypical mycobacteria

Localized lymphadenitis, necrotizing subcutaneous nodules,

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


139


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

2557

140

3

3.21 IRIS

Paradoxical IRIS

1.

2. 1

-

-

-

1

IRIS

-

-

-

-

-

Unmasking IRIS

1.

2.

3.

4. 1

- 3

-

IRIS

-

-

-

-


141


3.15

3.15.1 (acuteHIVinfection) 6(recentHIVinfection)

Early HIV infection

6

(acute HIV infection acute

retroviral syndrome)

anti-HIV inconclusive qualitative HIV

RNA p24Ag

6 (recent HIV infection)

sero conversion 6

6

anti-HIV positive

early HIV infection

CD4 cells count

functional cure

40-90 acute

retroviral syndrome

VL (

100,000 copies/mL)

2557

142

3

anti-HIV negative

positive 6

o NAT anti-HIV

window period anti-HIV ( 4

window period 3 )

o VL > 100,000 copies/mL p24Ag

/ anti-HIV inconclusive (negative or weakly

positive ELISA)

early HIV infection

early HIV infection

o

o

o

early HIV infection

early HIV infection

5


143


3.22 acute HIV infection

96

74

70

(erythematous maculopapular rash)

70

54

32

32

27

14

13

(thrush) 12

( aseptic meningitis, peripheral n

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