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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.
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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 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
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 Healthcare Workers with Documented and Possible Occupationally Acquired HIV Worldwide* * USA through 12/98 Other countries through 12/97
Types of Exposures Resulting in Occupational HIV Transmission US HCW reported through 12/98
Source Fluids for Exposures Resulting in Occupational HIV Transmission US HCW reported through 12/98
Risk Factors For HIV TransmissionCDC 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
No infection Aborted infection Acute infection no immune memory cellular immune response seroconversion Outcomes of HIV Exposures
CTL Reactivity to HIV Envelope Peptides in HCWs with Percutaneous Exposure to HIV Source patientHCW 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
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 Animal Studies of PEP:Prevention of SIV in macaques with PMPA 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 patientHCW 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 regressionmodel
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
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 Indication for PEPNYSDOH 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 Prophylaxis RecommendationsNYSDOH CDC
Universal Regimen ZDV 3TC IDV or Nelf or efavirenz (nevirapine) Basic Regimen ZDV 3TC Expanded Regimen Basic IDV or Nelf Antiretroviral RegimensNYSDOH CDC
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.
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 Initiation of PEPNYSDOH CDC
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 (?)
Less expensive Less toxic greater compliance? Complex Imprecise definitions Basic regimen is inadequate if sero-conversion occurs CDC GuidelinesPro Con
Scientifically rational Simplified decision points Expensive Toxic Compliance issues Prolong uncertainty NYSDOH Pro Con
Controversies in PEP • CDC and NYS disagree ? • Legal ramifications • DOH regulated facility DOH guidelines
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 Treatment Failures in HCWs
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 ZDV PEP Failures in HCWs: United States
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 Failure of Four-Drug HIV PEP 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