1. HIV Transmission in Hospital Settings

2. Objectives Epidemiology of occupational HIV transmission Rationale for postexposure prophylaxis (PEP) NYSDOH / CDC recommendations Reality of PEP

3. U.S. Health-Care Workers with Documented Occupationally Acquired HIV Infection, by Occupation through December 1998 Occupation Clinical laboratory technician 16 Nurse 22 Physician6 Non-clinical laboratory technician 3 Surgical technician2 Autopsy technician1 Health aide / attendant 1 Housekeeper / maintenance worker 1 Respiratory therapist 1 Dialysis technician 1 Total 54

4. Healthcare Workers with Documented and Possible Occupationally Acquired HIV Worldwide* US54134188 France11 27 38 UK 4 9 13 Mexico 0 9 9 Italy5 0 5 Australia 4 0 4 Spain5 0 5 South Africa3 1 4 Germany3 3 6 Others 7 7 14 Total96190286 * USA through 12/98 Other countries through 12/97

5. Types of Exposures Resulting in Occupational HIV Transmission US HCW reported through 12/98

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

7. Risk Factors For HIV Transmission CDC Case Control Study Risk FactorOdds Ratio Deep Injury15 Visible blood 6 In vessel 4 Terminal illness 6 ZDV use0.2 Cardo et al., NEJM;1997;337:1485-90

8. Average Risk of HIV Infection to HCWs by Exposure Route Percutaneous 0.3% Mucous membrane 0.1% Non-intact skin<0.1%

9. Rationale for PEP Window of opportunity… Animal studies Human studies

10. Outcomes of HIV Exposures No infection  Aborted infection  Acute infection  no immune memory cellular immune response seroconversion

12. 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

13. 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

14. Animal Studies of PEP: Prevention of SIV in macaques with PMPA Initiation / duration % Protected 24h / 28d100% 48h / 28d 50% 72h / 28d 50% 24h / 10d 75% 24h / 3d 0 Tsai et al, J Virol, 1998;72:4265

15. 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

16. 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

17. ZDV Reduces CTL Response 20 HCW  (HIV+ SP)  7 Rx ZDV13 No ZDV (1 CTL +)(6 CTL +) D’Amico, Infect Control Hosp Epidemiol 1999;20:428

18. PEP in Humans / HCW CDC Case Control Study –33 cases / 679 controls –Identify risk factors –Logistic regression model

19. Logistic Regression Analysis of Risk Factors For HIV Transmission Risk FactorOdds Ratio Deep Injury15 Visible blood 6 In vessel 4 Terminal illness 6 ZDV use0.2

20. CDC Case Control Study cases(%)controls(%) First dose < 4 hrs6789 Completed 4 wks4466 1000 mg ZDV7578 Receiving ZDV7170

21. Limitations of CDC Study Study design Bias Small numbers of cases Non-standard ZDV use

22. Designing a PEP Program Indications Timing Drugs Testing

23. 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

24. Prophylaxis Recommendations NYSDOH CDC Independent of source patient and the severity of the exposure Treat mucocutaneous and percutaneous the same 2 NRTI + PI (or NNRTI) Dependent upon specific character- istics 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

25. Antiretroviral Regimens NYSDOH CDC Universal Regimen ZDV 3TC IDV or Nelf or efavirenz (nevirapine) Basic Regimen ZDV 3TC Expanded Regimen Basic IDV or Nelf

26. Recommended PEP Regimen 2 ZDV 300 mg po bid + Epivir150 mg po bid + PI 1 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.

27. Initiation of PEP NYSDOH 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

28. HIV Testing Methods –ELISA –PCR (viral load) Concerns –accuracy –time to positive Effect of PEP

29. HIV Testing ELISA method Baseline 4-6 weeks 12 weeks 6 months 1 year (?)

30. CDC Guidelines Pro Con Less expensive Less toxic greater compliance? Complex Imprecise definitions Basic regimen is inadequate if sero- conversion occurs

31. NYSDOH Pro Con Scientifically rational Simplified decision points Expensive Toxic Compliance issues Prolong uncertainty

32. Controversies in PEP CDC and NYS disagree ? –Legal ramifications DOH regulated facility  DOH guidelines

33. 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

34. ZDV PEP Failures in HCWs: United States Hrs to ZDV Rx AcuteTime SP on Exposure Rx DoseDays RVI ?to SC ZDV? Bx needle.51000* 45 23d23d yes hollow needle.75 80010 14d90d yes glass 1.5 60010 21d73dyes hollow needle 2 100017 38d121dno IV cannula 3-710008 36d94dyes mucocutaneous 192120021 75d134d? hollow needle.67 ?42 70d83dyes hollow needle 11000 5 16d20dYes

35. 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

36. Implications of PEP Failures PEP does not eliminate transmission risk Not just “resistance”

37. Reality of PEP Uncertain science Rapid evaluation / implementation Adverse effects  compliance

38. Conclusion Epidemiology of occupational HIV transmission Rationale for postexpsoure prophylaxis (PEP) NYSDOH recommendations for PEP Reality of PEP

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