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“An Ounce of Prevention…
… is worth a pound of cure.” –B. Franklin
Categories of HIV Exposure Prophylaxis
(“..the last shall be first.” –Matthew 19:30)
Similar to our understanding of HIV/AIDS
-Starting with AIDS and working back to
HIV (a RETRO-virus)
-Starting with PCP treatment, back to
TMP/SMX prophylaxis
Post-Exposure (PEP - Occupational, Maternal
to Child – a forecast of Pre?)
Post-Exposure (nPEP – Non-Occupational)
Pre-Exposure (PREP - ?Both)
HIV: OCCUPATIONAL PEP
History
ZDV FDA-approved to treat HIV, March 1987
CDC publishes first PEP statement 1990; no
specific recommendations
1995 case-control study shows 79% reduction
when ZDV used post-exposure
Guidelines published 1996
Recommended combination antiretroviral
therapy for high-risk significant exposures
Prevention
The most effective approach is not to put
yourself at risk at all!!
Use good infection control procedures at all
times
Wear gloves if you are likely to be contaminated
with body fluids (take gloves with you)
Think about what you will do in the event of an
injury before it happens
HIV is Fragile
Common substances, including hot water, soap,
bleach and alcohol, will kill it.
Air dries the fluid that contained the virus
which destroys the virus within a few hours
How long HIV can survive outside the body
depends on
*the amount of HIV present in the body fluid;
*what conditions the fluid is subjected to
Risk after exposure
Risk of acquiring HIV infection following
occupational exposure to HIV infected blood
is low.
Average risk for HIV transmission after
percutaneous exposure to HIV infected blood
in healthcare settings is approx 1 per 300
After mucocutaneous exposure, <1 in 1000.
No risk of transmission where intact skin is
exposed to HIV infected blood
Calculating HIV seroconversion risk
after needlestick/sharps injury
Known HIV+. Risk is 1 in 300
HIV serostatus unknown - where prevalence of
HIV in local/hospital population is:
– 1 in 3 (ie 30%). Risk is 300 x 3 = 1 in 900
– 1 in 10 (ie 10%). Risk is 300 x10 = 1 in 3000
– 1 in 100 (ie 1%). Risk is 300 x 100 = 1 in 30,000
Risk of Transmission
Significant exposures to any of the following may
pose a risk for bloodborne pathogen (BBP)
transmission:
Blood, Semen, Vaginal secretions, Cerebrospinal
fluid, Synovial fluid, Pleural fluid, Peritoneal
fluid, Pericardial fluid, Amniotic fluid
Body fluids NON-risk if no visible blood include
urine, sputum, saliva, stool, emesis, nasal
discharge, tears, sweat
Exposure/Transmission Risk varies by pathogen:
(3,33,333)
HIV: 0.3% = 3/1,000, Hep C: 3% = 30/1,000,
Hep B: 30% = 300/1,000
PEP – occupational exposure
Four factors associated with an increased risk of
occupationally acquired HIV infection:
1. Deep injury
2. Visible blood on the device which caused the
injury
3. Injury with a needle from artery or vein
4. Terminal HIV illness in source patient
Almost all reported cases of HIV seroconversion have
occurred after injuries with hollow bore needles.
Body fluids and materials which may pose a
risk of HIV transmission
Amniotic fluid
Cerebrospinal fluid
Human breast milk
Pericardial fluid
Peritoneal fluid
Pleural fluid
Saliva in association with
dentistry
Synovial fluid
Unfixed human tissues and
organs
Vaginal secretions
Semen
Any other fluid if visibly
bloodstained
Fluid from burns or skin
lesions
HIV: Documented Seroconversions
Through June 2000
49: Blood
1: Visible bloody body fluid
3: Unspecified fluid
3: Concentrated virus in laboratory
N = 56
HIV: Seroconversion in Health Care
Workers
Primary HIV Infection
- Experienced in 81% of HCWs
- Occurred median 25 days after exposure
Seroconversion
- Exposure to seroconversion median 46 days
- Seroconversion by 6 months in 95% of HCWs
- 3 persons with seroconversion at 6-12 months
Risk Factors for HIV Seroconversion in
HCWs
Risk Factor Adjusted Odds
Ratio*
Deep Injury 15.0
Visible Blood on Device 6.2
Terminal Illness in Source Patient 5.6
Needle in Source Vein/Artery 4.3
PEP with Zidovudine (AZT) 0.2
*All Risk Factors were significant (P <
0.01)
Risk Assessment of Occupational Exposure
Ideally this should not be done by the injured
Health care Worker
Assessment of the injury involves
– Nature of the injury - was there significant
contamination?
– The risk the patient has HIV (Hep C,Hep
B)
• Known HIV+
• Person of unknown HIV serostatus
Circumstances of exposure
– Assess if exposure was significant
Types of exposure with contaminated
instruments/body fluids associated with
significant risk
1. Percutaneous injury (needles,
instruments, bites which break skin)
2. Exposure of broken skin (abrasions, cuts)
3. Exposure of mucous membranes inc. the
eye, mouth
Risk Assessment of Occupational Exposure
The Source Patient
If of unknown HIV serostatus - A designated
doctor should approach the source patient
and ask for informed agreement to HIV
testing (This should not be the exposed
worker)
Risk Assessment of Occupational Exposure
Evaluate the source and the exposure
Is the source material blood or
instrument contaminated with blood or
potentially infectious material?
YES
NO No PEP needed
What type of exposure occurred?
Percutaneous exposure
Intact skin
Mucous membrane or non intact skin
No PEP needed
Assess volume Assess volume
Small
Few drops and/or short
duration
Large
Several drops, major
blood splash and/or long
duration of several
minutes or more
Less severe
Solid needle,
superficial scratch
More severe
Large bore hollow needle ,
deep puncture, visible
blood on device, source
needle used in artery or
vein.
PEP Steps
1:Manage the injury
2:Report and record the incident
3:Evaluate the exposed person
4:Evaluate the source patient
5:PEP
6:follow up
Universal Precautions
Refers to a method of infection control in which
all human blood and other potentially
infectious materials are treated as if known to
be infectious for HIV and HBV and HCV.
Universal precautions do not apply to feces,
nasal secretions, sputum, sweat, tears, urine
or vomitus unless they contain visible blood.
Universal Precautions
Using protective equipment when applicable, to
protect the skin and mucous membranes.
The mandatory use of gloves, gowns, masks
and eye protection if any worker is handling
bio-hazardous waste.
The washing of hands after handling bio-
hazardous waste.
Immediate action following a
contamination incident
Wound or non-intact skin to be washed liberally
with soap and water without scrubbing
Antiseptics should not be used as no evidence of
efficacy and effect on local defences
unknown
Free bleeding encouraged
If mucous membranes contaminated - irrigate
with water and remove contact lenses
Immediately after exposure to
blood
Flush splashes to the nose, mouth or skin with
water
Irrigate eye with clean water, saline or sterile
irriguants
REPORT the exposure
Finding a Needle
HIV can live a long time in a used needle Hep
B and C can live even longer!
Needle sticks can transmit Hepatitis more easily
than HIV
If you find a needle with an exposed point, pick
it up very carefully (with tweezers or tape)
and put it in a sharps container.
Disposal of used Needles
Seattle Solid Waste Utility Brochure
Post Exposure Protocol
What is your protocol?
1) Needlestick or a cut: washed with soap and water.
Splashes to nose, mouth, or skin: flushed with water.
Eyes: irrigated with sterile water.
2) Report exposure to supervisor.
3) Discuss post-exposure treatment with medical
provider. Hep B: vaccine & HBIG
HIV: Post Exposure Prophylaxis
When should PEP be started?
efficacy of PEP thought to wane with time
at what point is PEP “no longer worth it”?
benefits of PEP
risks of PEP
exposure
time
Timing of PEP: CDC Guidelines
Initiate as soon as possible (within hours)
Interval after which there is no benefit for
humans is undefined
“If appropriate for the exposure, PEP should
be started even when the interval since
exposure exceeds 36 hours”
Obtain expert advice when interval has
exceeded 36 hours
MMWR 1998;47:RR-7.
HIV PEP: Percutaneous Exposure
DHS/PEP Rx/PP
Source Infection Status
Exposure Type
Less Severe
More Severe
HIV+ Class 1
Less Severe: eg. solid needle, superficial injury
More Severe: eg. Large-bore hollow needle, deep puncture, visible blood on device,
or needle used in patient’s artery or vein
Class 1: Asymptomatic or low HIV RNA (<1500)
Class 2: Symptomatic or known high HIV RNA
HIV+ Class 2
Basic (2 Drugs) Expanded (3 Drugs)
Expanded (3 Drugs) Expanded (3 Drugs)
From: CDC. MMWR 2001;50 (RR11):1-42.
Post-Exposure HIV Prophylaxis
(PEP)
PEP can reduce the risk of infection up to 81% (CDC,
2001)
DHHS recommends 4-week course, 2 drugs (e.g.
ZDV/3TC or EFV/FTC) for most exposures, or 3
drugs (Add e.g. LPV/r) for high risk exposures, e.g.
large volume of blood, or deep puncture, or known
HIV positive source, or drug-resistant HIV.
Updated U.S. Public Health Service Guidelines for the
Management of Occupational Exposures to HBV,
HCV, and HIV and Recommendations for
Postexposure Prophylaxis, September 26, 2005 /
54(RR-9);1-17. Available online at:
http://aidsinfo.nih.gov/guidelines/default_db2.asp?id=67
HIV PEP: Mucous Membrane
Exposure
DHS/PEP Rx/PP
Source Infection Status
Exposure Type
Small Volume
Large Volume
HIV+ Class 1
Class 1: Asymptomatic or low HIV RNA (<1500)
Class 2: Symptomatic or known high HIV RNA
HIV+ Class 2
Consider Recommend
Basic (2 Drugs) Basic (2 Drugs)
Recommend Recommend
Basic (2 Drugs) Expanded(3 Drugs)
From: MMWR 2001;50 (RR-11):1-42.
Source of Unknown HIV Status
- Generally, no PEP warranted; however
consider basic 2-drug PEP for sources
with HIV risk factors.
Unknown Source
- Generally, no PEP warranted; however
consider basic 2-drug PEP in settings
where exposure to HIV-infected persons is
likely.
HIV Postexposure Prophylaxis
Source Unknown or Status of Source
Unknown
HIV PEP Rx: Basic Regimen
Basic Regimen
Zidovudine (ZDV, AZT) +
Lamivudine (3TC)
300 mg bid or 200 mg tid
150 mg bid
Alternate Basic Regimen
Didanosine (ddI) +
Stavudine (d4T)
Dose
Stavudine (d4T) +
Lamivudine (3TC)
400 mg qd (250 mg qd if < 60 kg)
40 mg bid (30 mg bid if <60 kg)
Dose
200 mg bid (125 mg bid if < 60 kg)
150 mg bid
HIV PEP Rx: Expanded Regimen
Expanded Regimen
Basic Regimen + One of Following
Medication
Indinavir (IDV)
Nelfinavir (NFV)
Efavirenz (EFV)
Abacavir (ABC)
800 mg q8h
750 mg tid or 1250 mg bid
600 mg qd
300 mg bid
Dose
CTL Responses to HIV Exposure in
HCWs
Situation
HCW exposed to HIV+ source
-Took AZT PEP
-Did not take PEP
HCW exposed to HIV-source
7/20 (35%)
1/7 (14%)
6/13 (46%)
0/20 (0%)
CTL Response
Failure of Combination HIV PEP Rx
Regimen
ZDV + ddI
ZDV + ddI
*3 Drugs
ZDV + ddI + 3TC + IDV
ddI + d4T + NVP
Yes
No
Yes (not resistant)
Yes (resistant)
Yes (resistant)
Source on ARV Meds
*ZDV + 3TC + IDV x 48h, then d4T + 3TC + IDV
“From a theoretical perspective, risk stratification is
sensible; however, from a practical perspective,
these issues are often murky. For individuals who
believe they have experienced an occupational
HIV exposure, offering less than the presumably
most effective regimen may seem objectionable.
Thus, in our institution (NIH), we tend to offer the
3-drug regimen, including a protease inhibitor....”
- DK Henderson-
Occupational HIV Exposure: PEP Follow-
Up
HIV Antibody Testing: Baseline, 6w, 12w, 6m, +/-
12m
Routine use of HIV RNA: not recommended
Drug Toxicity Monitoring: baseline and at 2 weeks
Sexual abstinence or condom use (especially in
first 6-12 weeks after exposure)
Avoid Pregnancy
A 39-year-old nurse sticks herself in the finger with
a needle used to draw blood from an HIV-infected
patient. The source patient’s most recent CD4
count was 135 cells/mm
3
and HIV RNA 26,400;
the source patient is on AZT + 3TC + Indinavir
and is about to go on a new regimen.
a) What PEP regimen would you recommend?
“If the source-person’s virus is known or
suspected to be resistant to one or more of
the drugs included in the PEP regimen, the
selection of drugs to which the source
patient’s virus is unlikely to be resistant is
recommended.”
- Centers for Disease Control and Prevention-
HIV PEP
Current EAGA recommendations for UK Health care
workers seconded overseas:
– In areas where no anti HIV treatment is
available for patients
– 2 Drug combination
– Zidovudine 250mg and Lamivudine
150mg bd (Combivir 1 tablet bd) for 28
days
HIV PEP
– BUT
– AntiHIV treatment is being rolled out to the local
population in many developing countries (parts of Uganda,
Malawi, Botswana etc)
– In these areas anti-HIV treatments are likely to be readily
available to staff who have significant occupational injuries
(ask your supervisor!)
– Drug resistant HIV likely to be present in local population
– 3 Drug combination recommended for exposures to
‘treatment experienced’ HIV population
– Zidovudine 250mg + Lamivudine 150mg bd (Combivir 1
tablet bd) + Kaletra 2 tablets bd for 28 days
– PEP should ideally be started within 1 hour of the injury
Costs
Combivir 1 bd
– 7 days = £78.96
– 28 days = £315.84
Combivir 1 bd + Kaletra 2 tablets bd
– 7 days = £176.45
– 28 days =£709.63
– Recommend 7 day pack
WARNING
The sale of anti HIV drugs, as with any prescription
drugs, to a third party is illegal, may result in
criminal prosecution and proceedings by the
General Medical Council.
Disposal of unused supplies of antiHIV drugs are
recommended on your return to the UK after your
elective. This can be arranged through any
pharmacy.
It is unsafe to purchase or use any drug prescribed for
another person
Nelfinavir
This agent was previously recommended and
prescribed as HIV PEP
In the last month it has been withdrawn by the
Roche Pharmaceuticals as some UK supplies
have been contaminated with a carcinogen.
Please hand any supplies of this drug that you
have to any pharmacy for disposal.
PEP FINAL.pdf

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PEP FINAL.pdf

  • 1.
  • 2. “An Ounce of Prevention… … is worth a pound of cure.” –B. Franklin
  • 3. Categories of HIV Exposure Prophylaxis (“..the last shall be first.” –Matthew 19:30) Similar to our understanding of HIV/AIDS -Starting with AIDS and working back to HIV (a RETRO-virus) -Starting with PCP treatment, back to TMP/SMX prophylaxis Post-Exposure (PEP - Occupational, Maternal to Child – a forecast of Pre?) Post-Exposure (nPEP – Non-Occupational) Pre-Exposure (PREP - ?Both)
  • 5. History ZDV FDA-approved to treat HIV, March 1987 CDC publishes first PEP statement 1990; no specific recommendations 1995 case-control study shows 79% reduction when ZDV used post-exposure Guidelines published 1996 Recommended combination antiretroviral therapy for high-risk significant exposures
  • 6. Prevention The most effective approach is not to put yourself at risk at all!! Use good infection control procedures at all times Wear gloves if you are likely to be contaminated with body fluids (take gloves with you) Think about what you will do in the event of an injury before it happens
  • 7. HIV is Fragile Common substances, including hot water, soap, bleach and alcohol, will kill it. Air dries the fluid that contained the virus which destroys the virus within a few hours How long HIV can survive outside the body depends on *the amount of HIV present in the body fluid; *what conditions the fluid is subjected to
  • 8. Risk after exposure Risk of acquiring HIV infection following occupational exposure to HIV infected blood is low. Average risk for HIV transmission after percutaneous exposure to HIV infected blood in healthcare settings is approx 1 per 300 After mucocutaneous exposure, <1 in 1000. No risk of transmission where intact skin is exposed to HIV infected blood
  • 9. Calculating HIV seroconversion risk after needlestick/sharps injury Known HIV+. Risk is 1 in 300 HIV serostatus unknown - where prevalence of HIV in local/hospital population is: – 1 in 3 (ie 30%). Risk is 300 x 3 = 1 in 900 – 1 in 10 (ie 10%). Risk is 300 x10 = 1 in 3000 – 1 in 100 (ie 1%). Risk is 300 x 100 = 1 in 30,000
  • 10. Risk of Transmission Significant exposures to any of the following may pose a risk for bloodborne pathogen (BBP) transmission: Blood, Semen, Vaginal secretions, Cerebrospinal fluid, Synovial fluid, Pleural fluid, Peritoneal fluid, Pericardial fluid, Amniotic fluid Body fluids NON-risk if no visible blood include urine, sputum, saliva, stool, emesis, nasal discharge, tears, sweat Exposure/Transmission Risk varies by pathogen: (3,33,333) HIV: 0.3% = 3/1,000, Hep C: 3% = 30/1,000, Hep B: 30% = 300/1,000
  • 11. PEP – occupational exposure Four factors associated with an increased risk of occupationally acquired HIV infection: 1. Deep injury 2. Visible blood on the device which caused the injury 3. Injury with a needle from artery or vein 4. Terminal HIV illness in source patient Almost all reported cases of HIV seroconversion have occurred after injuries with hollow bore needles.
  • 12. Body fluids and materials which may pose a risk of HIV transmission Amniotic fluid Cerebrospinal fluid Human breast milk Pericardial fluid Peritoneal fluid Pleural fluid Saliva in association with dentistry Synovial fluid Unfixed human tissues and organs Vaginal secretions Semen Any other fluid if visibly bloodstained Fluid from burns or skin lesions
  • 13. HIV: Documented Seroconversions Through June 2000 49: Blood 1: Visible bloody body fluid 3: Unspecified fluid 3: Concentrated virus in laboratory N = 56
  • 14. HIV: Seroconversion in Health Care Workers Primary HIV Infection - Experienced in 81% of HCWs - Occurred median 25 days after exposure Seroconversion - Exposure to seroconversion median 46 days - Seroconversion by 6 months in 95% of HCWs - 3 persons with seroconversion at 6-12 months
  • 15. Risk Factors for HIV Seroconversion in HCWs Risk Factor Adjusted Odds Ratio* Deep Injury 15.0 Visible Blood on Device 6.2 Terminal Illness in Source Patient 5.6 Needle in Source Vein/Artery 4.3 PEP with Zidovudine (AZT) 0.2 *All Risk Factors were significant (P < 0.01)
  • 16. Risk Assessment of Occupational Exposure Ideally this should not be done by the injured Health care Worker Assessment of the injury involves – Nature of the injury - was there significant contamination? – The risk the patient has HIV (Hep C,Hep B) • Known HIV+ • Person of unknown HIV serostatus
  • 17. Circumstances of exposure – Assess if exposure was significant Types of exposure with contaminated instruments/body fluids associated with significant risk 1. Percutaneous injury (needles, instruments, bites which break skin) 2. Exposure of broken skin (abrasions, cuts) 3. Exposure of mucous membranes inc. the eye, mouth Risk Assessment of Occupational Exposure
  • 18. The Source Patient If of unknown HIV serostatus - A designated doctor should approach the source patient and ask for informed agreement to HIV testing (This should not be the exposed worker) Risk Assessment of Occupational Exposure
  • 19. Evaluate the source and the exposure Is the source material blood or instrument contaminated with blood or potentially infectious material? YES NO No PEP needed What type of exposure occurred? Percutaneous exposure Intact skin Mucous membrane or non intact skin No PEP needed Assess volume Assess volume Small Few drops and/or short duration Large Several drops, major blood splash and/or long duration of several minutes or more Less severe Solid needle, superficial scratch More severe Large bore hollow needle , deep puncture, visible blood on device, source needle used in artery or vein.
  • 20. PEP Steps 1:Manage the injury 2:Report and record the incident 3:Evaluate the exposed person 4:Evaluate the source patient 5:PEP 6:follow up
  • 21. Universal Precautions Refers to a method of infection control in which all human blood and other potentially infectious materials are treated as if known to be infectious for HIV and HBV and HCV. Universal precautions do not apply to feces, nasal secretions, sputum, sweat, tears, urine or vomitus unless they contain visible blood.
  • 22. Universal Precautions Using protective equipment when applicable, to protect the skin and mucous membranes. The mandatory use of gloves, gowns, masks and eye protection if any worker is handling bio-hazardous waste. The washing of hands after handling bio- hazardous waste.
  • 23. Immediate action following a contamination incident Wound or non-intact skin to be washed liberally with soap and water without scrubbing Antiseptics should not be used as no evidence of efficacy and effect on local defences unknown Free bleeding encouraged If mucous membranes contaminated - irrigate with water and remove contact lenses
  • 24. Immediately after exposure to blood Flush splashes to the nose, mouth or skin with water Irrigate eye with clean water, saline or sterile irriguants REPORT the exposure
  • 25. Finding a Needle HIV can live a long time in a used needle Hep B and C can live even longer! Needle sticks can transmit Hepatitis more easily than HIV If you find a needle with an exposed point, pick it up very carefully (with tweezers or tape) and put it in a sharps container.
  • 26. Disposal of used Needles Seattle Solid Waste Utility Brochure
  • 27. Post Exposure Protocol What is your protocol? 1) Needlestick or a cut: washed with soap and water. Splashes to nose, mouth, or skin: flushed with water. Eyes: irrigated with sterile water. 2) Report exposure to supervisor. 3) Discuss post-exposure treatment with medical provider. Hep B: vaccine & HBIG HIV: Post Exposure Prophylaxis
  • 28. When should PEP be started? efficacy of PEP thought to wane with time at what point is PEP “no longer worth it”? benefits of PEP risks of PEP exposure time
  • 29. Timing of PEP: CDC Guidelines Initiate as soon as possible (within hours) Interval after which there is no benefit for humans is undefined “If appropriate for the exposure, PEP should be started even when the interval since exposure exceeds 36 hours” Obtain expert advice when interval has exceeded 36 hours MMWR 1998;47:RR-7.
  • 30. HIV PEP: Percutaneous Exposure DHS/PEP Rx/PP Source Infection Status Exposure Type Less Severe More Severe HIV+ Class 1 Less Severe: eg. solid needle, superficial injury More Severe: eg. Large-bore hollow needle, deep puncture, visible blood on device, or needle used in patient’s artery or vein Class 1: Asymptomatic or low HIV RNA (<1500) Class 2: Symptomatic or known high HIV RNA HIV+ Class 2 Basic (2 Drugs) Expanded (3 Drugs) Expanded (3 Drugs) Expanded (3 Drugs) From: CDC. MMWR 2001;50 (RR11):1-42.
  • 31. Post-Exposure HIV Prophylaxis (PEP) PEP can reduce the risk of infection up to 81% (CDC, 2001) DHHS recommends 4-week course, 2 drugs (e.g. ZDV/3TC or EFV/FTC) for most exposures, or 3 drugs (Add e.g. LPV/r) for high risk exposures, e.g. large volume of blood, or deep puncture, or known HIV positive source, or drug-resistant HIV. Updated U.S. Public Health Service Guidelines for the Management of Occupational Exposures to HBV, HCV, and HIV and Recommendations for Postexposure Prophylaxis, September 26, 2005 / 54(RR-9);1-17. Available online at: http://aidsinfo.nih.gov/guidelines/default_db2.asp?id=67
  • 32. HIV PEP: Mucous Membrane Exposure DHS/PEP Rx/PP Source Infection Status Exposure Type Small Volume Large Volume HIV+ Class 1 Class 1: Asymptomatic or low HIV RNA (<1500) Class 2: Symptomatic or known high HIV RNA HIV+ Class 2 Consider Recommend Basic (2 Drugs) Basic (2 Drugs) Recommend Recommend Basic (2 Drugs) Expanded(3 Drugs) From: MMWR 2001;50 (RR-11):1-42.
  • 33. Source of Unknown HIV Status - Generally, no PEP warranted; however consider basic 2-drug PEP for sources with HIV risk factors. Unknown Source - Generally, no PEP warranted; however consider basic 2-drug PEP in settings where exposure to HIV-infected persons is likely. HIV Postexposure Prophylaxis Source Unknown or Status of Source Unknown
  • 34. HIV PEP Rx: Basic Regimen Basic Regimen Zidovudine (ZDV, AZT) + Lamivudine (3TC) 300 mg bid or 200 mg tid 150 mg bid Alternate Basic Regimen Didanosine (ddI) + Stavudine (d4T) Dose Stavudine (d4T) + Lamivudine (3TC) 400 mg qd (250 mg qd if < 60 kg) 40 mg bid (30 mg bid if <60 kg) Dose 200 mg bid (125 mg bid if < 60 kg) 150 mg bid
  • 35. HIV PEP Rx: Expanded Regimen Expanded Regimen Basic Regimen + One of Following Medication Indinavir (IDV) Nelfinavir (NFV) Efavirenz (EFV) Abacavir (ABC) 800 mg q8h 750 mg tid or 1250 mg bid 600 mg qd 300 mg bid Dose
  • 36. CTL Responses to HIV Exposure in HCWs Situation HCW exposed to HIV+ source -Took AZT PEP -Did not take PEP HCW exposed to HIV-source 7/20 (35%) 1/7 (14%) 6/13 (46%) 0/20 (0%) CTL Response
  • 37. Failure of Combination HIV PEP Rx Regimen ZDV + ddI ZDV + ddI *3 Drugs ZDV + ddI + 3TC + IDV ddI + d4T + NVP Yes No Yes (not resistant) Yes (resistant) Yes (resistant) Source on ARV Meds *ZDV + 3TC + IDV x 48h, then d4T + 3TC + IDV
  • 38. “From a theoretical perspective, risk stratification is sensible; however, from a practical perspective, these issues are often murky. For individuals who believe they have experienced an occupational HIV exposure, offering less than the presumably most effective regimen may seem objectionable. Thus, in our institution (NIH), we tend to offer the 3-drug regimen, including a protease inhibitor....” - DK Henderson-
  • 39. Occupational HIV Exposure: PEP Follow- Up HIV Antibody Testing: Baseline, 6w, 12w, 6m, +/- 12m Routine use of HIV RNA: not recommended Drug Toxicity Monitoring: baseline and at 2 weeks Sexual abstinence or condom use (especially in first 6-12 weeks after exposure) Avoid Pregnancy
  • 40. A 39-year-old nurse sticks herself in the finger with a needle used to draw blood from an HIV-infected patient. The source patient’s most recent CD4 count was 135 cells/mm 3 and HIV RNA 26,400; the source patient is on AZT + 3TC + Indinavir and is about to go on a new regimen. a) What PEP regimen would you recommend?
  • 41. “If the source-person’s virus is known or suspected to be resistant to one or more of the drugs included in the PEP regimen, the selection of drugs to which the source patient’s virus is unlikely to be resistant is recommended.” - Centers for Disease Control and Prevention-
  • 42. HIV PEP Current EAGA recommendations for UK Health care workers seconded overseas: – In areas where no anti HIV treatment is available for patients – 2 Drug combination – Zidovudine 250mg and Lamivudine 150mg bd (Combivir 1 tablet bd) for 28 days
  • 43. HIV PEP – BUT – AntiHIV treatment is being rolled out to the local population in many developing countries (parts of Uganda, Malawi, Botswana etc) – In these areas anti-HIV treatments are likely to be readily available to staff who have significant occupational injuries (ask your supervisor!) – Drug resistant HIV likely to be present in local population – 3 Drug combination recommended for exposures to ‘treatment experienced’ HIV population – Zidovudine 250mg + Lamivudine 150mg bd (Combivir 1 tablet bd) + Kaletra 2 tablets bd for 28 days – PEP should ideally be started within 1 hour of the injury
  • 44. Costs Combivir 1 bd – 7 days = £78.96 – 28 days = £315.84 Combivir 1 bd + Kaletra 2 tablets bd – 7 days = £176.45 – 28 days =£709.63 – Recommend 7 day pack
  • 45. WARNING The sale of anti HIV drugs, as with any prescription drugs, to a third party is illegal, may result in criminal prosecution and proceedings by the General Medical Council. Disposal of unused supplies of antiHIV drugs are recommended on your return to the UK after your elective. This can be arranged through any pharmacy. It is unsafe to purchase or use any drug prescribed for another person
  • 46. Nelfinavir This agent was previously recommended and prescribed as HIV PEP In the last month it has been withdrawn by the Roche Pharmaceuticals as some UK supplies have been contaminated with a carcinogen. Please hand any supplies of this drug that you have to any pharmacy for disposal.