UPDATE IN HIV POST-EXPOSURE PROPHYLAXISbamras.ddc.moph.go.th/userfiles/PEP_(2).pdf · Current PEP guideline ... Paramedic started on AZT, 3TC, and lopinavir/rtv. Two days later, he

UPDATE IN HIV POST-EXPOSURE

PROPHYLAXIS

Weerawat Manosuthi

Outline

Case scenario of postexposure prophylaxis

Risks of and how to manage postexposure

prophylaxis

Current PEP guideline

US PHS 2013

New York guideline 2012

Thai guideline 2010

WHO 2007

CDC 2005

Case presentation 1

Male paramedic splashed with large volume of

bloody amniotic fluid onto open ulcers on his arm.

He has DM II, HT, DLP, GERD, CKD, peripheral

neuropathy.

Source is HIV+ without any treatment during this

pregnancy.

Paramedic started on AZT, 3TC, and lopinavir/rtv.

Two days later, he complains of overwhelming

nausea and vomiting.

Case Presentation 2

Nurse stuck with a needle found on the floor of a patient’s room.

Patient in that room is HIV infected with VL >750,000. He had complex ARV Hx, marked with lots of non-adherence. His current regimen was AZT, 3TC and EFV.

Nurse was started on AZT, 3TC, and NVP.

Nurse’s friend recommended changing to AZT, d4T and Kaletra.

Case Presentation 3

Phlebotomist stuck with vacutainer needle while

transferring blood. Wearing gloves. Deep stick.

Source is HIV+, and Hepatitis C +. Started on AZT,

TDF and lopinavir/rtv one month ago when VL

>750,000 and CD4 73. His doctor thinks adherence is

good.

Three months before starting new regimen, genotype

while on d4T, 3TC, efavirenz had shown M184V and

K103N.

Who is the most frequently reported

occupational acquired HIV infection?

1. Nurses

2. Physicians

3. Lab technicians

4. House keepers

Occupational Acquired HIV infection 1985-

2001

Do A, et al. Infect Control Hosp Epidemiol 2003;24:86-96.

45 HCPs who reported accidental injuries in

BIDI

• On exposed person analysis, 7.5% (3 of 40), 2.9% (1 of 34), 0% were

positive for HBsAg, Anti-HCV and Anti-HIV, respectively.

• Seven of 45 (15.5%) events were severe exposures.

• 24 % (22of 45) of staffs initiated HIV PEP.

• 16 % initiated within 1 hour after exposure and half of them continued HIV

PEP until 4 weeks.

• 53% (24 of 45) of staffs had previous history of HBV vaccination.

2005 2007 2007

2014

2012

2013

Postexposure Management

Step Management

1 Exposure site management

2 Exposure reporting

3 Evaluation of transmission

risk

4 Counseling

5 Consideration of PEP

6 Follow-up


Step Management




risk

4 Counseling


6 Follow-up

Exposure Site Management

Wound and skin: washed with soap and water

Mucous membrane: flushed with water

No evidence of benefit for:

Application of antiseptics or disinfectants

Squeezing (“milking”) puncture sites

Avoid use of bleach and other agents caustic to

skin


Step Management


2 Exposure reporting (1-4)


risk

4 Counseling


6 Follow-up

Exposure Report 1

(1) Details of “procedure being performed”

Date and time of exposure

Where and how exposure occurred

Type and brand of device

How and when in course of handling device

(2) Details of “exposure”

Type and amount of fluid, severity of exposure

Percutaneous: depth of injury whether fluid was injected

Skin or mucous membrane: estimated volume of material, condition of skin

Exposure Report 2

(3) Details of “exposure source”

Source of material contained HBV, HCV or HIV?

If HIV-infected: stage of disease, history of ARV, viral load,

ARV resistance

(4) Details of “exposed person”

Anti HIV, Anti HBV, Anti HCV status

Hepatitis B vaccination & vaccine response


Step Management




risk

4 Counseling


6 Follow-up

Evaluation of Transmission Risk 3

Type of HIV transmission Risk of transmission per exposure

event

Blood transfusion 0.95

Perinatal exposure 0.13

Needle sharing (IVDU) 0.0067

Needle stick 0.032 (0.3%, 95%CI 0.2-0.5%)

Unprotected receptive anal intercourse 0.005 - 0.032

Needle sharing 0.0032

Unprotected receptive vaginal

intercourse 0.001 - 0.003

Mucous membrane exposure 0.0009 (0.09%, 95%CI 0.006-0.5%)

Unprotected insertive vaginal intercourse 0.003 - 0.0009

Ingestion of human milk 0.00001 - 0.00004

Potential fluid Non Potential fluid Blood Feces

Body fluid containing visible

blood

Sweat

CSF Nasal secretion

Pleural fluid Tears

Semen, Vg secretion Saliva

Synovial fluid Urine

Pleural fluid Sputum

Peritoneal fluid Vomitus

Pericardial fluid

Amniotic fluid

Human bite

Direct contact

Factors Associated with Transmission after

Percutaneous Exposure

NEJM 1997; 337:1485-90.

Postgrad Med J 2003,79:324-8.

10/12 New York State Department of Health AIDS Institute: www.hivguidelines.org 38

APPENDIX D. LOGISTIC REGRESSION ANALYSIS OF RISK FACTORS FOR HIV

INFECTION AFTER PERCUTANEOUS EXPOSURE TO HIV-INFECTED BLOOD

Logistic Regression Analysis of Risk Factors for HIV Infection After Percutaneous Exposure to

HIV-Infected Blood

Risk Factor US Casesa All Cases

b

Adjusted odds ratio (95% CI)c

Deep injury 16.1 (6.1-44.6)

Visible blood on device 5.2 (1.8-17.7)

Procedure involving needle in artery or vein 5.1 (1.9-14.8)

Terminal illness in source patientd 6.4 (2.2-18.9)

Postexposure use of zidovudine 0.2 (0.1-0.6)

Reprinted from Cardo DM, Culver DH, Ciesielski CA, et al. A case-control study of HIV seroconversion in health

care workers after percutaneous exposure: Centers for Disease Control and Prevention Needlestick Surveillance

Group. N Engl J Med 1997;337:1485-1490. [PubMed]

a All risk factors were significant (P < 0.02).

b All risk factors were significant (P < 0.01).

c Odds ratios are for the odds of seroconversion after exposure in workers with the risk factor as compared with

those without it. d Terminal illness was defined as disease leading to the death of the source patient from AIDS within two months

after the health care worker’s exposure.

1.

2.

3.

4.

Average Risk for Transmission of

HIV, HBV, and HCV after Needle stick

Source Risk HBV

HBeAg+

HBeAg-

22.0% - 30.0%

1.0% - 6.0%

HCV+ 1.8%

HIV+ 0.3%


Step Management




risk

4 Counseling


6 Follow-up

HIV Postexposure Counseling

1. Possible side effects of PEP drugs

2. Possible drug interactions

3. Adherence

4. Signs and symptoms of acute HIV infection

Fever, rash ,flu-like illness

5. Prevention of secondary transmission

Sexual abstinence or condom use

No blood/tissue donation

Transmission and PEP drug risks if breastfeeding

No work restriction indicated


Step Management




risk

4 Counseling


6 Follow-up

Risk of Adverse Effects Risk of Transmission

Considerations When Using PEP

PEP

Initiation of HIV PEP

If indicated, start PEP as soon as possible after exposure

Regard as an urgent medical concern

Hours rather than days

Interval after which PEP is no longer likely to be effective in humans is unknown

Initiating PEP days or weeks after an exposure might be considered if warranted for increased risk exposure

Animal Studies of PEP: Prevention of SIV in macaques with Tenofovir

Tsai et al, J Virol, 1998;72:4265

Initiation / duration % Protected

24h / 28d 100%

48h / 28d 50%

72h / 28d 50%

24h / 10d 75%

24h / 3d 0%

Tsai et al, J Virol 1998;72:4265.

CDC 2005: Definitions

• HIV-Positive, Class 1= Asymptomatic or low viral load

• HIV-Positive, Class 2 = Symptomatic, AIDS, acute seroconversion, high viral load

• Less severe = Solid needle and superficial injury

• More severe = Large-bore hollow needle, deep puncture, visible blood on device, needle used in artery/vein

• Small volume = A few drops

• Large volume = Major blood splash

Type

Infection status of source

HIV-Positive

Class 1

HIV-Positive

Class 2

Source

of unknown HIV

status Unknown source

Less

severe

Recommended

basic 2-drug PEP

Recommended

expanded 3-drug

PEP

Generally, no PEP;

consider basic 2-

drug PEP for source

with HIV risk

Generally, no PEP;

consider basic 2-drug

PEP in settings where

exposure to HIV-

infected persons is

likely

More

severe

Recommended

expanded

3-drug PEP

Recommended

expanded

3-drug PEP

MMWR Recomm Rep 2005; Sep 30; 54(RR-9):1-7.

• HIV-Positive, Class 1= Asymptomatic or low viral load


• Less severe = Solid needle and superficial injury

• More severe = Large-bore hollow needle, deep puncture, visible blood on device, needle used in artery/vein

PEP for Percutaneous Injuries

Type

Infection status of source

HIV-Positive

Class 1

HIV-Positive

Class 2

Source

of unknown HIV

status Unknown source

Small

volume

Consider basic

2-drug PEP

Recommended

basic 2-drug PEP

Generally, no PEP

Generally, no PEP

Large

volume

Recommended

basic

2-drug PEP

Recommended

expanded

3-drug PEP

Generally, no PEP;

consider basic 2-

drug PEP for

source with HIV

risk

Generally, no PEP;

consider basic 2-drug

PEP in settings where

exposure to HIV-

infected persons is

likely

• HIV-Positive, Class 1 = Asymptomatic or low viral load


• Small volume = A few drops

• Large volume = Major blood splash


PEP for Mucous Membrane and Non-intact Skin Exposures

2-drug Regimen

3-drug Regimen

WHO Guideline 2007

1

2

1

2

Which Drugs to Use?

Basic 2-drug regimens:

CDC

Preferred:

ZDV + 3TC

TDF + 3TC or FTC

Alternative:

d4T + 3TC

ddI + 3TC


Basic 2-drug regimens:

WHO

• Preferred:

– ZDV + 3TC

• Alternative:

– TDF + 3TC

– d4T + 3TC

Expanded ≥3-drug PEP regimens: Preferred:

LPV/RTV (Kaletra) + basic 2-drug regimen

New York Guideline 2012. www.hivguideline.org.


Figure 1. PEP Following Occupational Exposure

a Depending on the test used, the window period may be shorter than 6 weeks. Clinicians should contact appropriate

laboratory authorities to determine the window period for the test that is being used. b If the source is known to be HIV-infected, information about his/her viral load, ART medication history, and

history of antiretroviral drug resistance should be obtained when possible to assist in selection of a PEP regimen.9

Initiation of the first dose of PEP should not be delayed while awaiting this information and/or results of

resistance testing. When this information becomes available, the PEP regimen may be changed if needed in

consultation with an experienced provider.

c See Appendix A for dosing recommendations in patients with renal impairment.

Two-drug regimen is not recommended.


Table 3

Recommended Regimen for HIV PEP Following Occupational Exposure a

Tenofovir

b 300 mg PO qd + Emtricitabine

b,c 200 mg PO qd

Plus

Raltegravir

d 400 mg PO bid

a When the source is known to be HIV-infected, past and current ART experience, viral load data, and genotypic or

phenotypic resistance data (if available) may indicate the use of an alternative PEP regimen. Consult with a clinician

experienced in managing PEP. See Tables 4 and 5. b The dosing of tenofovir and emtricitabine/lamivudine should be adjusted in patients with baseline creatinine

clearance <50 mL/min (see Appendix A for dosing recommendations). Tenofovir should be used with caution in

exposed workers with renal insufficiency or who are taking concomitant nephrotoxic medications. Fixed-dose

combinations should not be used in patients who need dose adjustment due to renal failure. c Lamivudine 300 mg PO qd may be substituted for emtricitabine. However, a fixed-dose combination is available

when tenofovir is used with emtricitabine (Truvada 1 PO qd).

d The dosing of raltegravir should be adjusted when co-administered with rifampin (see Appendix A for dosing

recommendations).

A. Duration of PEP Regimen

RECOMMENDATIONS:

When the source patient is confirmed to be HIV-negative, clinicians should discontinue the

PEP regimen before completion (see Section V.C: HIV Testing of the Source Patient).

If the exposed worker’s baseline test shows evidence of HIV infection acquired before the

exposure and initiation of PEP, decisions regarding continuation of ART should be based

on current treatment guidelines (see Antiretroviral Therapy). However, the PEP regimen

should not be discontinued until the positive result is repeated with a confirmatory assay.

If the exposed worker’s week 4 post-exposure HIV test results are indeterminate or the

exposed worker has symptoms suggestive of acute HIV infection, clinicians should continue

ART beyond 28 days until a definitive diagnosis is established.

The recommended 28-day treatment duration is based on limited animal data and expert

opinion.19

When the source patient is confirmed to be HIV-negative, the PEP regimen should be

discontinued before completion (see Section V.C: HIV Testing of the Source Patient).

If at any time acute HIV infection is suspected, consultation with a clinician experienced in

managing acute HIV infection should occur immediately (also see Diagnosis and Management

of Acute HIV Infection). Clinicians who do not have access to experienced HIV clinicians should

call the National Clinicians’ Consultation Center PEP Line at 1-888-448-4911. When using the

PEP Line, providers from New York State should identify themselves as such.


Recommended Regimen for HIV PEP

AZT is no longer recommended.


Preferred Alternative PEP Regimens

Antiretroviral Drugs to Avoid

Drugs to avoid Reasons Efavirenz - CNS side effects are common

- Complicating the need to provide a first dose at

any time of the day

- Should be avoided in pregnant women

- Substantial efavirenz resistance

Nevirapine - Severe hepatotoxicity

Abacavir - Hypersensitivity reactions

Stavudine and Didanosine - Possibility of toxicities

Nelfinavir and Indinavir -Poorly tolerated

CCR5 co-receptor

antagonists

- Lack of activity against potential

CXCR4 tropic virus


US PHS Guideline 2013

Infection Control Hospital Epidimiology 2013;34:875-892.





Thai

Guideline

2014

Prefered basic

regimens

Alternative basic

regimens

Expanded

regimens

AZT/3TC d4T/3TC PI: LPV/r, IDV/r,

ATV/r, SQV/r

TDF/3TC ddI/3TC NNRTI: EFV

TDF/FTC

Thai Guideline 2010

Thai Guideline 2014 Antiretroviral Regimens Remarks

A TDF + 3TC/FTC + Rilpivirine

TDF + 3TC/FTC + Lopinavir/r

TDF + 3TC/FTC + Atazanavir/r

B TDF +3TC/FTC + Raltegravir

TDF + 3TC/FTC + Efavirenz

C Use AZT for regimen A or B If GFR < 60

Prefered basic

regimens

Alternative basic

regimens

Expanded

regimens

AZT/3TC d4T/3TC PI: LPV/r, IDV/r,

ATV/r, SQV/r

TDF/3TC ddI/3TC NNRTI: EFV

TDF/FTC

Thai Guideline 2010

Drug-drug Interactions!

Drug-drug interactions

Consideration of PEP

PEP during pregnancy

Efavirenz is NOT recommended during pregnancy

because of possible teratogenicity?

Cases of fatal lactic acidosis in pregnant women

treated with d4T and ddI reported

Indinavir should not be given shortly before delivery

because of hyperbilirubinemia

New York 2012: How to Follow-up


US PHS 2013: How to Follow-up


Thai Guideline 2014

Case presentation 1

Male paramedic splashed with large volume of

bloody amniotic fluid onto open ulcers on his arms.

He has DM II, HT, DLP, GERD, CKD, peripheral

neuropathy.

Source is HIV+ without any treatment during this

pregnancy.

Paramedic started on AZT, 3TC, and lopinavir/rtv.

Two days later he complains of overwhelming

nausea and vomiting.

Management

Assess injury: Large volume exposure to skin with compromised integrity.

Assess source: Known HIV+, likely high viral load, but virus also likely wild-type.

Recommend management: Manage symptoms using anti-emetics and consider pro-motility agent for diabetic gastroparesis. Consider other regimens: AZT/3TC/RTV/PI, AZT/3TC/EFV. Consider drug interactions.

Case Presentation 2

Nurse stuck with a needle found on the floor of a patient’s room.

Patient in that room is HIV infected with VL >750,000. He had complex ARV Hx, marked with lots of non-adherence. His current regimen was AZT, 3TC and EFV.

Nurse was started on AZT, 3TC, and NVP.

Nurse’s friend recommended changing to AZT, d4T and Kaletra.

Management

Assess injury: No characteristics of the needle available. Stick not deep.

Assess source: Unknown source. Consider how likely it is that needle came from HIV+ source.

Recommend management: If it is likely that this needle was used on an HIV+ patient recently, a full course of PEP is recommended, with choice of drugs taking into account possible resistance. Kaletra may maintain activity against resistant virus, but AZT and d4T not recommended in combination because of

clinical and in vitro antagonism.

Case Presentation 3

Phlebotomist stuck with vacutainer needle while

transferring blood. Wearing gloves. Deep stick.

Source is HIV+, and Hepatitis C +. Started on AZT,

TDF and lopinavir/rtv one month ago when VL

>750,000 and CD4 73. His doctor thinks adherence

is good.

Three months before starting new regimen, genotype

while on d4T, 3TC, efavirenz had shown M184V and

K103N.

Management

Recommend management: Recommend regimen for HIV PEP. 3TC likely ineffective.

Protease inhibitor resistance unlikely to have developed during one month of therapy.

Consider AZT, TDF, lopinavir/rtv (same as source regimen), as option most likely to combine effectiveness with tolerability.

Follow closely for Hepatitis C seroconversion.

Summary of PEP Recommendation

Thai 2014 US PHS

2013

New York

2012

WHO 2007

CDC 2005

Time to

initiate PEP

< 72 hrs ASAP, <72 hrs Prefer <2 hrs, < 36

hrs

< 72 hrs <72 hrs

Preferred

PEP

LPV/r

ATV/r

RPV

TDF/FTC

TDF /3TC

RAL TDF/FTC

RAL TDF/FTC

LPV/r AZT/3TC

LPV/r

AZT/3TC

TDF /3TC

TDF/FTC

Alternative

PEP

RAL

EFV

AZT/3TC RAL

DRV/r

ATV/r

LPV/r

ETR

RPV

TDF/FTC

TDF/3TC

AZT/3TC

AZT/FTC

DRV/r

ATV/r

FPV/r

TDF/FTC

ATV/r

SQV/r

APV/r

TDF/FTC

d4T/3TC

ATV/r

FPV/r

IDV/r

SQV/r

NFV

EFV

d4T/3TC

ddI/3TC

Summary of HIV Test Recommendation

GUIDELINES Baseline Wk 4 Wk 6 Wk 12 Wk 16 Wk 24 Wk 48*

Thai 2014 X X X

US PHS 2013 X X X

New York 2012 X X X

WHO 2007 X X X

CDC 2005

X X

X

X

*In case of HCV co-infection

THANK YOU

Documents

UPDATE IN HIV POST-EXPOSURE PROPHYLAXISbamras.ddc.moph.go.th/userfiles/PEP_(2).pdf · Current PEP guideline ... Paramedic started on AZT, 3TC, and lopinavir/rtv. Two days later, he