105/01/08 醫事人員暴露愛滋病後之處理原則

Jan 8, 2016

Outline

( )

) vs.

(

Four opportunities for HIV prevention

Exposed(precoital/coital) Exposed Unexposed (postcoital) Behavioural and structural interventions • Circumcision • Condoms • STD treatment Years

Vaccines ART PrEP • Oral (TDF/FTC*) • Topical • Injectable microbicides Hours

Vaccines ART PEP

72 hours

Lancet 2013;382:1515-24

Infected Treatment of HIV to reduce infectivity

Years

AIDS Acquired Immune Deficiency Syndrome

(HIV)

(HIV)

AIDS脢 8-10

Secondary Syphilis

(ELISA)

(Western blot)

(Viral load)

Diagnostic Tests for HIV Approved by the US Food and Drug Administration Test Category/Test Detection of viral antigens

Clinical Use Diagnostic aid

Used to evaluate symptomatic HIV disease and as a screening test in blood donors to reduce the “window period�

Monitor HIV progression and effectiveness of antiretroviral therapy

Useful in diagnosis of acute HIV infection in high-risk patient with a negative or indeterminate Western blot test. A low-level positive viral load may be a false positive.

Diagnostic aid

Highly specific but relatively insensitive, due to varying degrees of viremia and technical difficulties

p24 antigens

Viral nucleic acid detection PCR and branchedchain DNA assays

Viral culture HIV HIV culture

Comments

ELISA window period Generation of ELISA test

Component

Approximate window period

1

Infected cell lysates

63d

2

Recombinant protein 42d and peptides

3

Sandwich with labeled antigen

22d

4

Combination p24 antigen detection and sandwich

16d

•无有效的根治手段 •无有效的HIV疫苗预防 •早期、及时和准确的诊断是关键

CD4

HIV

Antiretroviral Agents Classes Nucleoside/nucleotide RTI

Non-nucleoside RTI

Protease inhibitors

ZDV

Nevirapine

Saquinavir

ddI

Delavirdine

Ritonavir

ddC

Efavirenz

Indinavir

d4T

Etravirine

Nelfinavir

3TC

Amprenavir

Fusion inhibitors

ABC ZDV/3TC

Lopinavir/ritonavir Enfuvirtide

ZDV/3TC/ABC Tenofovir

CCR antagonists

TDF/FTC

Integrase inhibitors

Fos-Amprenavir Tipranavir Darunavir

Emtricitabine ABC/3TC

Atazanavir

Maraviroc/ Vicriviroc

Raltegravir/ Elvitegravir

• 2

(NRTIs) (nNRTIs)

• 2

(NRTIs) (PIs)

• 3

(NRTIs)

1

1 -2

• 10 • • CD4+ • •

5-10 /mL 100-150

/mL

AIDS

HIV/AIDS 2 MSM脢( 75.5%

)

(15 24 )

IDUs(

)

4000

2005 3500

2004

3000

1990 2000

2500 2000 1500

2009

1989 1995 HIV1/2 (HIV-1/2 Ab)

1988

2003

(HIV1000

1 Ab)

500

1991 • •

1997

2006

(MSM,SW..)

0 84' 85' 86' 87' 88' 89' 90' 91' 92' 93' 94' 95' 96' 97' 98' 99' 00' 01' 02' 03' 04' 05' 06' 07' 08' 09'

-. . . . .

-

HIV

(

)

2015 2 4

HIV Percutaneous (blood)

0.3%

Mucocutaneous (blood)

0.09%

Receptive anal intercourse

1 - 30%

Insertive anal intercourse

0.1-10%

Receptive vaginal intercourse

0.1 – 10%

Insertive vaginal intercourse

0.1 – 1%

Receptive oral (male) Female-female orogenital IDU needle sharing Vertical (no prophylaxis)

0.06% 4 case reports 0.67% 24%

Estimating per-act HIV transmission risk: a systematic review. AIDS 2014;28:1509-19

Estimating per-act HIV transmission risk: a systematic review. AIDS 2014;28:1509-19

Estimating per-act HIV transmission risk: a systematic review. AIDS 2014;28:1509-19

J Virol 1998;72:4265-73

First cell target: dendritic cells in lamina propia J Exp Med 1996;183:215-25

Assessment of Post-Exposure Prophylaxis Risk of HIV infection

Source of exposure (HIV) infectivity of body fluids Mucosa integrity Time since exposure to HIV PEP (72-hours) Regimen of HIV PEP

Basic regimen Advanced regimen (drug resistance rate>15%) Education and psychological support Follow-up HIV tests and PEP side effects

HIV – – – – – – – •

MMWR Recomm Rep 1998; 47: 1-33

PEP HIV HIV

PEP

PEP

PEP脢; HIV

PEP脢; ,

PEP HIV

, PEP

PEP

PEP

PEP

PEP脢; HIV

PEP脢; ,

PEP HIV

, PEP

PEP

MMWR 2005 CDC

(1) 1) (2)

• 暴露來源病患HIV感染狀態 感染狀態， 暴露來源病患 感染狀態，區分第一級（ 區分第一級（ class 1） ）與第二級（ ） 與第二級（class 2） – 第一級:指沒有臨床症狀的 感染， 第一級 指沒有臨床症狀的HIV感染 指沒有臨床症狀的 感染，或者是病 患血中的病毒濃度低於1,500 RNA copies/mL 患血中的病毒濃度低於 第二級:指有臨床症狀的 感染， 第二級 指有臨床症狀的HIV感染 指有臨床症狀的 感染，或已進展到愛滋 病，或是病患為急性HIV感染 感染， 或是病患為急性 感染，或是病患血中的 病毒濃度很高

Risk Factors for Seroconversion Following Needle-sticks • CDC-sponsored case-control study • 33 cases, 665 controls with needlesticks from confirmed HIV+ source patients Risk Factor Deep injury Visibly bloody device Device in artery/vein Terminally ill SP AZT PEP

Odds Ratio* 15 6.2 4.3 5.6 0.19

NEJM 1997;337:1485-90

95% CI 6.0 – 41 2.2 – 21 1.7 – 12 2.0 – 16 0.06 – 0.52

PEP 暴露來源病患HIV感染狀況 感染狀況 暴露來源病患

暴露種類 感染狀況 第一級

少量暴露

大量暴露

第二級

建議使用

建議使用

基本PEP 基本

基本PEP 基本

建議使用

建議使用

基本PEP 基本

加強PEP 加強

病患感染狀況 不詳

不知來源

未感染HIV 未感染

病患

通常不需要使 用PEP ;但若來 但若來 源病患有感染 HIV危險性時 危險性時, 危險性時 可考慮使用基 本PEP

通常不需要使 用PEP ;但若推 但若推 測可能來源病 患有感染HIV危 危 患有感染 險性時,可考慮 險性時 可考慮 使用基本PEP 使用基本

不需使用 PEP

通常不需要使 用PEP ;但若來 但若來 源病患有感染 HIV危險性時 危險性時, 危險性時 可考慮使用基 本PEP

通常不需要使 用PEP ;但若推 但若推 測可能來源病 患有感染HIV危 危 患有感染 險性時,可考慮 險性時 可考慮 使用基本PEP 使用基本

不需使用 PEP

MMWR 2005 CDC

暴露量

(1)例如幾滴的血液或具傳染性的體液 例如幾滴的血液或具傳染性的體液。 例如幾滴的血液或具傳染性的體液。 (2)例如大量的血液潑灑到 例如大量的血液潑灑到。 例如大量的血液潑灑到。

Management of Exposures Follow-up of HIV: – Source anti-HIV (+): • Testing for anti-HIV at 6 weeks, 3 months, and 6 months (1 year for HCV sero-conversion) • Testing for anti-HIV if illness compatible with an acute retroviral illness occurs.

– Source anti-HIV (-) and no evidence of AIDS and acute HIV infection: • No indication of follow-up testing

Laboratory Tests Generally Recommended for Persons after Exposure to HIV. Test

Recommended during Treatment

Recommended at Follow-up

Baseline

Symptom Directed

4-6 Wk

12 Wk

24 Wk

Yes

Yes

Yes

Yes

Yes

Yes

Yes

No

No

No

HIV viral load

No

Yes

No

No

No

Anti-HBs antibodies

Yes

No

No

No

No

HBsAg

Yes

No

No

No

No

ELISA for HIV antibodies Creatinine, liver function, and complete blood count with differential count

HCV antibodies

No Yes

HCV RNA

No

Yes

Yes Yes

Yes

Yes

Yes

Yes

Screening, including rapid plasma Yes reagin test, for other sexually transmitted infections

No Yes

No Yes

HCWs

HIV

HIV 25

81% (

) 46 (

65

:95% :100%脢 HCV

)

Number of Percutaneous Injuries (PCIs) PCI Per 10000 inpatient-Days Job Category

injuries

95%CI

Nurse

2.43

1.81-3.06

Medical doctor

0.23

0.09-0.37

Medical technologist 0.20

0.07-0.33

Support personnel

0.12

0.02-0.23

Others

0.21

0.10-0.32

Shiao et al. Research in Nursing and Health 2008;31:172-9

103 104 104 75%

97

103 9797 - 103年 103 年 針 扎 ( 含 血 體 液 噴 濺 ) 事 件 及 發 生 率

件數 及發生率

140 120

128 11 5

114

106

102

113

98

100 80

40

含血液、 體液噴濺 件數

20

針扎發生 率%

60

1.97

1.58

1.95

1.75

98 年 度

99 年 度

10 0 年 度

1.47

1.74

1.72

102 年 度

103 年 度

0 97年 度

年度

101 年 度

97

103 97 - 103 年 針 扎 ( 含 血 體 液 噴 濺 ) 事 件

140 120

20 7

100

29

14 16

19 13

80 60

108

107 86

40

體液噴濺件數

101 85

97

94 針扎件數

20

年度

件數 0

97年度

98年度

99年度

100年度 101年度 102年度 103年度

103

1.72%。 1.72%。

1.103 94 30%脢(29/94) 2.

22%脢(21/94) 3.

32%脢(30/94) 4.

10%( 0.2%) 17%脢( 2.3%) 73%脢( 5.3%)

HIV

100 1 103 3

102 4

(

)

HIV , 24 , PEP

1

( ,

,

0.9%NS

..)

( ) 1.HBV VDRL 2.

3.

HCV

HIV

(

)

( 正 面

反 面

)

CD4

HIV

PEP regimens • 加強PEP係指基本 係指基本 加強 PEP再加上下列任一 再加上下列任一

• 基本PEP 基本

• Zidovudine+lamivudine • LPV/RTV • Abacavir+lamivudine

• ATV/RTV

• Tenofovir+lamivudine

• EFV • RAL

CDC脢

• DRV/RTV

Recommended Regimens for Postexposure Prophylaxis for Adults and Adolescents, • A 2-drug PEP regimen is effective, but 3 drugs are preferred.

• TDF + 3TC (or FTC) is recommended as the preferred backbone • LPV/r or ATV/r are suggested as the preferred third drug • RAL, DRV/r, or EFV can be considered as alternative options.

WHO Guidelines for HIV PEP CID2015;60(S3):S161-4

CID 2015;60(S3):S170-6

Exposure to a source patient with an undetectable serum VL • The risk is very low, PEP should still be offered. • Persistence of HIV in latently infected cells, has been demonstrated and such cells might transmit infection even in the absence of viremia.

Follow –up evaluation within 72hr of exposure • Make certain that the exposed HCP has a clear understanding of the risks for infection and the risks and benefits of PEP • Ensure that continued treatment with PEP is indicated • Increase adherence to HIV PEP regimens • Manage associated symptoms and side effects more effectively • Provide an early opportunity for ancillary medications or regimen changes • Improve detection of serious adverse effects • Improve the likelihood of follow-up serologic testing for a larger proportion of exposed personnel to detect infection.

US public health service guideline Infect Control Hosp Epidemiol 2013;34:875-92

Exposed personnel should be advised • Use precautions (eg, use of barrier contraception and avoidance of blood or tissue donations, pregnancy, and, if possible, breastfeeding) to prevent secondary transmission • Psychological counseling

US public health service guideline Infect Control Hosp Epidemiol 2013;34:875-92

Follow-Up of HCP Exposed to Known or Suspected HIV–Positive Sources (1) • Counseling (at the time of exposure and at follow-up appointments). Exposed HCP should be advised to use precautions to prevent secondary transmission, especially during the first 6–12 weeks after exposure.

• Possible drug toxicities (eg, rash and hypersensitivity reactions that could imitate acute HIV seroconversion and the need for monitoring) • • Possible drug interactions • • The need for adherence to PEP regimens US public health service guideline Infect Control Hosp Epidemiol 2013;34:875-92

Follow-Up of HCP Exposed to Known or Suspected HIV–Positive Sources (2) • Early reevaluation after exposure.

• Regardless of whether a healthcare provider is taking PEP, reevaluation of exposed HCP within 72 hours after exposure is strongly recommended

US public health service guideline Infect Control Hosp Epidemiol 2013;34:875-92

Follow-Up of HCP Exposed to Known or Suspected HIV–Positive Sources (3) • Follow-up testing and appointments.

• HIV testing at baseline and at 6 weeks, 12 weeks, and 6 months after exposure • 4th-generation combination HIV p24 antigen–HIV antibody test is being utilized, then HIV testing could be performed at baseline, 6 weeks after exposure, and 4 months after exposure • • CBC, renal and hepatic function tests (at baseline and 2 weeks after exposure ( and indicated ) US public health service guideline Infect Control Hosp Epidemiol 2013;34:875-92

Extended HIV follow up to 12 months • HCP who become infected with HCV after exposure to a source who is coinfected with HIV and HCV. • Unknown extended Duration-Exposure to a source coinfected with HIV and HCV in the absence of HCV seroconversion or for exposed persons with a medical history suggesting an impaired ability to mount an antibody response to acute infection US public health service guideline Infect Control Hosp Epidemiol 2013;34:875-92

HIV PEP regimens Preferred HIV PEP Regimen • TDF/FTC/RAL Alternative Regimens • Stribild (elvitegravir, cobicistat, tenofovir, emtricitabine) • (Truvada or TDF/3TC or Combivir or AZT+ FTC) plus ( RAL, DRV/r, ETR, RPV, ATV/r, LPV/r) US public health service guideline Infect Control Hosp Epidemiol 2013;34:875-92

(二 二)HIV針扎事件處理流程討論 針扎事件處理流程討論

2.因執行業務意外申請人類免疫缺乏病毒 因執行業務意外申請人類免疫缺乏病毒 預防性投藥之費用給付流程 (1)

• 依97年6月16日訂定發布之 2、5 1。 • 支付的項目如下 – 抗人類免疫缺乏病毒之藥品費 – 抗人類免疫缺乏病毒藥品之藥事服務費

8

(二 二)HIV針扎事件處理流程討論 針扎事件處理流程討論

2.因執行業務意外申請人類免疫缺乏病毒 因執行業務意外申請人類免疫缺乏病毒 預防性投藥之費用給付流程 (2)

• 申請單位應備文件 (抗人類免疫缺乏病毒藥品費及 其藥事服務費之收據 ) ( 抗人類免疫缺乏病毒藥品費及 其藥事服務費單項費用) 其藥事服務費單項費用) ( 針扎血液追蹤紀錄單(附件 針扎血液追蹤紀錄單 附件2) 附件

(二 二)HIV針扎事件處理流程討論 針扎事件處理流程討論

2.因執行業務意外申請人類免疫缺乏病毒 因執行業務意外申請人類免疫缺乏病毒 預防性投藥之費用給付流程 (3)

• 申請及撥款流程

：

– 申請單位具函檢附上述相關文件及領具提出申請 – 衛生署核定並函復撥款

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