Transcript HIV Transmission in Hospital Settings

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 Documented
Occupationally Acquired HIV Infection, by
Occupation through December 1998
Occupation
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*
US
France
UK
Mexico
Italy
Australia
Spain
South Africa
Germany
Others
Total
54
11
4
0
5
4
5
3
3
7
96
134
27
9
9
0
0
0
1
3
7
190
188
38
13
9
5
4
5
4
6
14
286
* USA through 12/98
Other countries through 12/97
Types of Exposures Resulting in
Occupational HIV Transmission
2
5
1
percutan
unk
both
mucocutan
46
US HCW reported through 12/98
N=54
Source Fluids for Exposures Resulting in
Occupational HIV Transmission
11
3
blood
vis bld fluid
unspec
conc virus
N=54
49
US HCW reported through 12/98
Risk Factors For HIV
Transmission
CDC Case Control Study
Risk Factor
Deep Injury
Visible blood
In vessel
Terminal illness
ZDV use
Cardo et al., NEJM;1997;337:1485-90
Odds Ratio
15
6
4
6
0.2
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 
no immune memory
• Aborted infection 
cellular immune
response
• Acute infection 
seroconversion
CTL Reactivity to HIV Envelope Peptides in
HCWs with Percutaneous Exposure to HIV
Source patient
HIV+ Exposed
HCW CTL
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
24h / 28d
48h / 28d
72h / 28d
24h / 10d
24h / 3d
% Protected
100%
50%
50%
75%
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
HIV+ Exposed
HCW CTL
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

7 Rx ZDV
(1 CTL +)
(HIV+ SP)

13 No ZDV
(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
Deep Injury
Visible blood
In vessel
Terminal illness
ZDV use
Odds Ratio
15
6
4
6
0.2
CDC Case Control Study
First dose < 4 hrs
Completed 4 wks
1000 mg ZDV
Receiving ZDV
cases(%)
67
44
75
71
controls(%)
89
66
78
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, nonintact skin or
percutaneous
exposure to blood or
visibly bloody fluid
• Source is potentially
HIV infected
• A mucous
membrane, nonintact skin or
percutaneous
exposure to blood or
visibly bloody fluid
• Source is potentially
HIV infected
Prophylaxis
Recommendations
NYSDOH
• Independent of
source patient and
the severity of the
exposure
Treat mucocutaneous and
percutaneous the same
• 2 NRTI + PI
(or NNRTI)
CDC
• Dependent upon
specific characteristics of the source
patient and the
exposure
Severe (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 Regimens
NYSDOH
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
+
Epivir
+
PI1 or efavirenz
300 mg po bid
150 mg po bid
1
Indinavir 800 mg po tid or nelfinavir 750 mg po
tid are suggested. Efavirenz 600 mg po daily as
single dose.
24
weeks total duration suggested.
Initiation of PEP
NYSDOH
CDC
• Up to 36 hours postexposure
(within 1 hour)
• Referral to “HIV
specialist” within 72
hours
• 1-2 hours up to 1-2
weeks postexposure
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 Guidelines
Pro
Con
• Less expensive
• Less toxic
greater compliance?
• Complex
• Imprecise definitions
• Basic regimen is
inadequate if seroconversion occurs
NYSDOH
Pro
• Scientifically rational
• Simplified decision
points
Con
•
•
•
•
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
Exposure
Bx needle
hollow needle
glass
hollow needle
IV cannula
mucocutaneous
hollow needle
hollow needle
Hrs to
ZDV
Rx
Acute
Time
SP on
Rx
.5
.75
1.5
2
3-7
192
.67
1
Dose
1000*
800
600
1000
1000
1200
?
1000
Days
45
10
10
17
8
21
42
5
RVI ?
23d
14d
21d
38d
36d
75d
70d
16d
to SC ZDV?
23d
yes
90d
yes
73d
yes
121d
no
94d
yes
134d
?
83d
yes
20d
Yes
Failure of Four-Drug HIV PEP
• Needle used in
art/vein
• Source patient
–
–
–
–
• PEP regimen
– ZDV/3TC/ddI/Ind - 6
weeks
– HIV- pre/post PEP
HIV+ and HCV+
Hx of Rx w/ d4T/3TC • Post PEP Course
– viral syndrome 4 wk
Current Rx ZDV/3TC
later
low CD4/ low viral
– HIV +, viral load >750K
load
– anti-HCV+/ HCV RNA – Virus - ZDV resistant
– 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
For more HIV-related resources,
please visit www.hivguidelines.org