HIV Transmission in Hospital Settings
Objectives
• Epidemiology of occupational HIV transmission
• Rationale for postexposure prophylaxis (PEP)
• NYSDOH / CDC recommendations
• Reality of PEP
U.S. Health-Care Workers with DocumentedOccupationally Acquired HIV Infection, by
Occupation through December 1998Occupation
Clinical laboratory technician 16
Nurse 22
Physician 6
Non-clinical laboratory technician 3
Surgical technician 2
Autopsy technician 1
Health aide / attendant 1
Housekeeper / maintenance worker 1
Respiratory therapist 1
Dialysis technician 1
Total 54
Healthcare Workers with Documented and Possible Occupationally Acquired HIV
Worldwide*
US54 134 188
France 11 27 38
UK 4 9 13
Mexico 0 9 9
Italy 5 0 5
Australia 4 0 4
Spain 5 0 5
South Africa3 1 4
Germany 3 3 6
Others 7 7 14
Total 96 190 286
* USA through 12/98 Other countries through 12/97
Types of Exposures Resulting in Occupational HIV Transmission
46
1
25
percutan
unk
both
mucocutan
N=54
US HCW reported through 12/98
Source Fluids for Exposures Resulting in Occupational HIV Transmission
49
1 1 3
blood
vis bld fluid
unspec
conc virus
N=54
US HCW reported through 12/98
Risk Factors For HIV Transmission
CDC Case Control Study
Risk Factor Odds Ratio
Deep Injury 15
Visible blood 6
In vessel 4
Terminal illness 6
ZDV use 0.2
Cardo et al., NEJM;1997;337:1485-90
Average Risk of HIV Infection to HCWs by Exposure Route
• Percutaneous 0.3%
• Mucous membrane 0.1%
• Non-intact skin <0.1%
Rationale for PEP
• Window of opportunity…
• Animal studies
• Human studies
Outcomes of HIV Exposures
• No infection
• Aborted infection
• Acute infection
no immune memory
cellular immune response
seroconversion
CTL Reactivity to HIV Envelope Peptides in HCWs with Percutaneous Exposure to HIV
Source patient HCW CTL
HIV+ Exposed 7/20 (35%)
HIV– Exposed 0/20 (0%)
Blood bank donors 0/7 (0%)
Adapted from Pinto et al, J Clin Invest 1995;96:867-76
Animal Studies of PEP: Prevention of SIV in macaques with
PMPA• 24 macaques
- 4 / study arm• IV inoculation of SIV
– 10 X 50% animal infectious dose
• Initiation at 24, 48, 72h post exp
• Duration 3,10, 28 days
Tsai et al, J Virol, 1998;72:4265
Animal Studies of PEP: Prevention of SIV in macaques with
PMPA
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
PEP in Humans
• 076 study– randomized– ZDV last trimester, intrapartum and
post-partum vs no rx– controls 25% rate of transmission
ZDV 7% rate of transmission
• Shorter courses…encouraging
CTL Reactivity to HIV Envelope Peptides in HCWs with Percutaneous Exposure to HIV
Source patient HCW CTL
HIV+ Exposed 7/20 (35%)
HIV– Exposed 0/20 (0%)
Blood bank donors 0/7 (0%)
Adapted from Pinto et al, J Clin Invest 1995;96:867-76
ZDV Reduces CTL Response
20 HCW (HIV+ SP)
7 Rx ZDV 13 No ZDV
(1 CTL +) (6 CTL +)
D’Amico, Infect Control Hosp Epidemiol 1999;20:428
PEP in Humans / HCW
• CDC Case Control Study
– 33 cases / 679 controls
– Identify risk factors
– Logistic regression model
Logistic Regression Analysis of Risk Factors For HIV
Transmission
Risk Factor Odds Ratio
Deep Injury 15
Visible blood 6
In vessel 4
Terminal illness 6
ZDV use 0.2
CDC Case Control Study
cases(%) controls(%)
First dose < 4 hrs 67 89
Completed 4 wks 44 66
1000 mg ZDV 75 78
Receiving ZDV 71 70
Limitations of CDC Study
• Study design
• Bias
• Small numbers of cases
• Non-standard ZDV use
Designing a PEP Program
• Indications
• Timing
• Drugs
• Testing
Indication for PEP NYSDOH CDC
• A mucous membrane, non-intact skin or percutaneous exposure to blood or visibly bloody fluid
• Source is potentially HIV infected
• A mucous membrane, non-intact skin or percutaneous exposure to blood or visibly bloody fluid
• Source is potentially HIV infected
Prophylaxis RecommendationsNYSDOH CDC
• Independent of source patient and the severity of the exposureTreat mucocutaneous and percutaneous the same
• 2 NRTI + PI
(or NNRTI)
• Dependent upon specific character-istics of the source patient and the exposureSevere (large bore, in source pt vessel, deep puncture)
Large volume (several drops or long duration)
High titer exposure (advanced AIDS, low CD4, high viral load)
• 2 NRTI PI
Antiretroviral RegimensNYSDOH CDC
Universal Regimen
ZDV
3TC
IDV or Nelf or
efavirenz (nevirapine)
Basic Regimen
ZDV
3TC
Expanded Regimen
Basic
IDV or Nelf
Recommended PEP Regimen2
ZDV 300 mg po bid +Epivir 150 mg po bid +PI1 or efavirenz
1 Indinavir 800 mg po tid or nelfinavir 750 mg po tid are suggested. Efavirenz 600 mg po daily as single dose.
2 4 weeks total duration suggested.
Initiation of PEPNYSDOH CDC
• Up to 36 hours post-exposure
(within 1 hour) • Referral to “HIV
specialist” within 72 hours
• 1-2 hours up to 1-2 weeks post-exposure
HIV Testing
• Methods– ELISA– PCR (viral load)
• Concerns– accuracy– time to positive
• Effect of PEP
HIV Testing
• ELISA method
• Baseline
4-6 weeks
12 weeks
6 months
1 year (?)
CDC GuidelinesPro Con
• Less expensive• Less toxic
greater compliance?
• Complex• Imprecise definitions• Basic regimen is
inadequate if sero-conversion occurs
NYSDOH Pro Con
• Scientifically rational• Simplified decision
points
• Expensive• Toxic• Compliance issues• Prolong uncertainty
Controversies in PEP
• CDC and NYS disagree ?– Legal ramifications
• DOH regulated facility
DOH guidelines
ZDV PEP Treatment Failures in HCWs
World-wide Cases• 18 failures in health
care providers • 5 failures in other
settings• no delay in time to
seroconversion• no adverse effects on
natural history
Potential Explanations• delay in treatment• dose too low / low drug
levels• resistant virus• high inoculum exposure• treatment duration too
short• zidovudine is not
efficacious
ZDV PEP Failures in HCWs: United States
Hrs to ZDV Rx Acute Time SP on
Exposure Rx Dose Days RVI ? to SC ZDV?
Bx needle .5 1000* 45 23d 23d yes
hollow needle .75 800 10 14d 90d yes
glass 1.5 600 10 21d 73d yes
hollow needle 2 1000 17 38d 121d no
IV cannula 3-7 1000 8 36d 94d yes
mucocutaneous 192 1200 21 75d 134d ?
hollow needle .67 ? 42 70d 83d yes
hollow needle 1 1000 5 16d 20d Yes
Failure of Four-Drug HIV PEP
• Needle used in art/vein
• Source patient – HIV+ and HCV+
– Hx of Rx w/ d4T/3TC
– Current Rx ZDV/3TC
– low CD4/ low viral load
– Virus - ZDV resistant
• PEP regimen– ZDV/3TC/ddI/Ind - 6
weeks – HIV- pre/post PEP
• Post PEP Course– viral syndrome 4 wk later– HIV +, viral load >750K– anti-HCV+/ HCV RNA -– HCW virus sensitive
Perdue B. et al, Retrovirus Conference, Poster 210
Implications of PEP Failures
• PEP does not eliminate transmission risk
• Not just “resistance”
Reality of PEP
• Uncertain science
• Rapid evaluation / implementation
• Adverse effects compliance
Conclusion
• Epidemiology of occupational HIV transmission
• Rationale for postexpsoure prophylaxis (PEP)
• NYSDOH recommendations for PEP
• Reality of PEP