HIV Transmission in Hospital Settings by anGlUa37

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									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             54      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 Africa   3        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

              5
          2
      1
                                 percutan
                                 unk
                                 both
                                 mucocutan


                                N=54
                      46



US HCW reported through 12/98
Source Fluids for Exposures Resulting in
    Occupational HIV Transmission

                  3
             11




                                    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                           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         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                         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                • A mucous
  membrane, non-            membrane, non-
  intact skin or            intact skin or
  percutaneous              percutaneous
  exposure to blood or      exposure to blood or
  visibly bloody fluid      visibly bloody fluid
• Source is potentially   • Source is potentially
  HIV infected              HIV infected
             Prophylaxis
          Recommendations
          NYSDOH                      CDC
• Independent of            • Dependent upon
  source patient and          specific character-
  the severity of the         istics of the source
  exposure                    patient and the
  Treat mucocutaneous and     exposure
  percutaneous the same       Severe (large bore, in source pt
                              vessel, deep puncture)
                              Large volume (several drops
                              or long duration)
• 2 NRTI + PI                 High titer exposure (advanced
  (or NNRTI)                  AIDS, low CD4, high viral load)


                            • 2 NRTI  PI
    Antiretroviral Regimens
   NYSDOH             CDC
Universal Regimen        Basic Regimen
ZDV                      ZDV
3TC                      3TC
IDV or Nelf or
efavirenz (nevirapine)   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.


24   weeks total duration suggested.
       Initiation of PEP
     NYSDOH            CDC
• Up to 36 hours post-    • 1-2 hours up to 1-2
  exposure                  weeks post-
  (within 1 hour)           exposure
• Referral to “HIV
  specialist” within 72
  hours
              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        • Complex
• Less toxic            • Imprecise definitions
  greater compliance?   • Basic regimen is
                          inadequate if sero-
                          conversion occurs
                  NYSDOH
          Pro                       Con
• Scientifically rational   •   Expensive
• Simplified decision       •   Toxic
  points                    •   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          Potential Explanations
• 18 failures in health   • delay in treatment
  care providers          • dose too low / low drug
• 5 failures in other          levels
  settings                • resistant virus
• no delay in time to
                          • high inoculum exposure
  seroconversion
                          • treatment duration too
• no adverse effects on
  natural history           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                         • PEP regimen
  art/vein                                     – ZDV/3TC/ddI/Ind - 6
• Source patient                                 weeks
  – HIV+ and HCV+                              – HIV- pre/post PEP
  – Hx of Rx w/ d4T/3TC • Post PEP Course
  – Current Rx ZDV/3TC    – viral syndrome 4 wk
  – low CD4/ low viral      later
    load                  – HIV +, viral load >750K
  – Virus - ZDV resistant – 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

								
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