UPDATE IN HIV POST-EXPOSURE
PROPHYLAXIS
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
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
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
Occupational Acquired HIV infection
1985-2001
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.
2014
2012
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
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
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
Postexposure Management
Step
Management
1
Exposure site management
2
Exposure reporting (1-4)
3
Evaluation of transmission
risk
4
Counseling
5
Consideration of PEP
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
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
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 Casesb 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%
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
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
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
Risk of Adverse Effects Risk of Transmission
Considerations When Using 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%
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
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
• 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
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
• HIV-Positive, Class 2 = Symptomatic, AIDS, acute seroconversion, high viral load • Small volume = A few drops
• Large volume = Major blood splash
MMWR Recomm Rep 2005; Sep 30; 54(RR-9):1-7.
PEP for Mucous Membrane and
Non-intact Skin Exposures
2-drug Regimen 3-drug Regimen
WHO Guideline 2007
1 2 1 2Which Drugs to Use?
Basic 2-drug regimens:
CDC Preferred: ZDV + 3TC TDF + 3TC or FTC Alternative: d4T + 3TC ddI + 3TC
MMWR Recomm Rep 2005; Sep 30; 54(RR-9):1-7.
Basic 2-drug regimens:
WHO • Preferred: – ZDV + 3TC • Alternative: – TDF + 3TC – d4T + 3TC
Expanded ≥3-drug PEP regimens:
Preferred:
New York Guideline 2012. www.hivguideline.org.
10/12 New York State Department of Health AIDS Institute: www.hivguidelines.org 7
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.
10/12 New York State Department of Health AIDS Institute: www.hivguidelines.org 13
Table 3
Recommended Regimen for HIV PEP Following Occupational Exposure a
Tenofovirb 300 mg PO qd + Emtricitabineb,c 200 mg PO qd
Plus
Raltegravird 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.
New York Guideline 2012. www.hivguideline.org.
Recommended Regimen for HIV PEP
New York Guideline 2012. www.hivguideline.org.
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
US PHS Guideline 2013
US PHS Guideline 2013
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 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
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
New York 2012: How to Follow-up
US PHS 2013: How to Follow-up
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
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.
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 /3TCRAL 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
