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Post-Exposure Prophylaxis

Post-Exposure Prophylaxis. Antonio E. Urbina, M.D. Associate Medical Director St. Luke’s Roosevelt Hospital Center for Comprehensive Care. Lecture Overview. HIV Post-Exposure Prophylaxis (PEP) oPEP (occupational PEP) nPEP (non-occupational PEP) Rationale Guidelines

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Post-Exposure Prophylaxis

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  1. Post-Exposure Prophylaxis Antonio E. Urbina, M.D. Associate Medical Director St. Luke’s Roosevelt Hospital Center for Comprehensive Care

  2. Lecture Overview • HIV Post-Exposure Prophylaxis (PEP) • oPEP (occupational PEP) • nPEP (non-occupational PEP) • Rationale • Guidelines • Hepatitis B and C post-exposure protocols

  3. Needlestick and Sharps Injuries • >5.6 million workers at risk • >800,000 annually (NIOSH 2000) • 385,000 annually in US hospitals (CDC 2004) • Only half of these reported • 26-86% preventable by safer needle designs • Unclear if currently fewer

  4. Occupational HIV Infection • Occupationally-acquired HIV among HCW reported through 6/99 • 137 possible cases of HIV transmission • 57 documented cases of HIV infection CDC

  5. U.S. Health-Care Workers with DocumentedOccupationally Acquired HIV as of 6/99 Nurse 24 Clinical laboratory technician 16 Physician (non-surgeon) 6 Non-clinical laboratory technician 3 Surgical technician 2 Housekeeper/maintenance worker 2 Morgue technician 1 Emergency med technician/paramedic 1 Respiratory therapist 1 Dialysis technician 1 Total 57 Occupational cases now much rarer CDC

  6. Mechanism of HIV Occupational Seroconversion N = 57 CDC

  7. Body Fluid Associated with Occupational HIV Seroconversion US HCW reported through 6/99 N = 57 CDC

  8. Occupational Transmission Risk • Riskiest (>0.2%) • deep parenteral inoculation via hollow needle • parenteral inoculation with high viral titers • Less Risky (<0.1%) • small volume via non-hollow needle • mucosal exposure/non-intact skin exposure • Risk not identified • intact skin exposure • exposure to urine, saliva, tears, sweat

  9. Occupational HIV Infection • Factors influencing transmission • Amount of blood involved in exposure • Amount of virus in patient’s blood at time of exposure • 26/57 source patients in CDC 6/99 study had AIDS • Post-exposure prophylaxis

  10. Non-OccupationalEstimated Transmission Risk

  11. Cohen, JID, 2005

  12. Support for PEP Treatment Guidelines • Identified risk factors for HIV transmission • ACTG 076 Study • Decreased transmission by 67% • CDC International Case Control Study • MMWR 12/95 • Laboratory and animal models • No adequate human data on nPEP efficacy

  13. Risk Factors for HIV TransmissionCDC Case Control Study Risk FactorAdjusted Odds Ratio (95% CI) Deep Injury 15 (6.1-44.6) Visible blood 6 (1.8-17.7) Terminal illness 6 (2.2-18.9) In vessel 4 (1.9-14.8) ZDV use0.2(0.1-0.6) MMWR 12/95;Cardo et al., NEJM;1997;337:1485-90 (updated) *All Risk Factors were significant (P < 0.01)

  14. Rationale for PEP: Role of Pathogenesis • “Window of opportunity” - during which PEP may prevent viral replication • First 24 hours - dendritic cells in the mucosa and skin are initial targets of HIV • 24-48 hours - migration of these cells to regional lymph nodes • 5 days - virus detectable in peripheral blood

  15. Exposure to HIV at mucosal surface (sex) Day 0 Virus collected by dendritic cells, carried to lymph node Day 0-2 HIV replicates in CD4 cells, released into blood Day 4-11 Virus spreads to other organs Day 11 on Kahn JO, Walker BD. N Engl J Med. 1998;339:33-39.

  16. No infection: Aborted infection: Acute infection: no immune memory cellular immune response seroconversion Potential Outcomes of HIV Exposures

  17. Cytotoxic T Lymphocyte (CTL) Responses to HIV Exposure in HCWs CTL Response Situation HCW exposed to HIV- source HCW exposed to HIV+ source -Took AZT PEP -Did not take PEP 0/20 (0%) 7/20 (35%) 1/7 (14%) 6/13 (46%) D’Amico R, et al. Infect Control Hosp Epi 1999;20:428-30.

  18. Macaques and PMPA (Tenofovir) • Macaques injected with SIV • 28 days PMPA protective if initiated at 24 hours post-exposure • Infections seen: • initiation delayed 48-72 hours post-exposure • treatment duration shortened to 10 days • No efficacy if treatment duration 3 days J Virol 1998;72(5):4265-73 and 2000;74(20):9771-5

  19. Macaques and PMPA (Tenofovir) • Macaques exposed intravaginally to HIV-2 • Protection observed with 28-day course of PMPA given 12 and 36 hours after exposure • Infection observed if PMPA administration delayed until 72 hours after exposure J Virol 1998;72(5)4265-73 & 2000;74(20)9771-5.

  20. Animal Studies: Observed Outcomes • Suppression or delay of antigenemia • Early administration more effective than later • Larger inocula decrease prophylactic efficacy • Decreased antiviral doses decrease prophylactic efficacy

  21. CDC Guidelines • oPEP (occupational) • MMWR, 54 (RR-9), 9/30/05 • nPEP (non-occupational) • MMWR, 54 (RR-2), 1/21/05 • www.cdc.gov/mmwr NYS DOH Guidelines • oPEP (occupational) • January 2008 • October 2012 • nPEP (non-occupational) • January 2008 • Updated guidelines 2009: • Medical Care Criteria Committee of AIDS Institute • www.hivguidelines.org

  22. Key Elements of Post-Exposure Prophylaxis (PEP) Programs • Medical issues • Indications • Regimens • Follow-up • Programmatic issues • Awareness of need • Timely availability of medical evaluation and PEP agents • Availability of follow-up • Confidentiality and documentation

  23. 1. Assess Risk • Percutaneous injury • Contact of mucous membrane • Contact non-intact skin

  24. 1. Assess RiskAmount of Blood or Body Fluid Fluids with Risk • Blood or visibly bloody fluid • Semen • Vaginal secretions • Cerebrospinal fluid • Synovial fluid • Pleural fluid • Pericardial fluid • Amniotic fluid

  25. Bites • ~250,000 bites annually in U.S. • HIV levels in saliva very low • Documented transmission by blood-tinged saliva1,2 • Consider PEP when: • Blood exposure to biter and/or bitten person (e.g. source has bleeding gums or lesions) 1 Vidmar L et al. Lancet 1996;347:1762-1763. 2 Pretty I et al. Am J Forensic Med Pathol 1999;20:232-239.

  26. Community Needlestick Injuries • Consider: • HIV prevalence in the community or facility • Surrounding prevalence of injection drug use • Do not test discarded needles for HIV

  27. 1. Assess RiskNon-risky Fluids* • Saliva, sputum or nasal secretions • Tears • Sweat • Urine • Stool • Emesis *Unless there is visible blood

  28. Risk and PEP of Non-Occupational Exposures

  29. Key Updates • TRV+ RAL is now the PREFERRED regimen for all exposures of significant risk • Starting PEP ASAP, ideally within 2 hours • First dose should be given while SP being evaluated • If SP has had risks in the last 6 weeks, HIV VL should also be drawn • PEP should be continued until VL comes back undetectable

  30. Key Updates (2) Baseline HIV test should be conducted on EP whether or not they take HIV PEP If PEP indicated, follow-up HIV serology for EP @ 4 weeks and 12 weeks 24 week test no longer recommended

  31. Table 2: Exposures for Which PEP Is Indicated Break in the skin by a sharp object (including hollow-bore, solid-bore, and cutting needles or broken glassware) that is contaminated with blood, visibly bloody fluid, or other potentially infectious material, or that has been in the source patient’s blood vessel. Bite from a patient with visible bleeding in the mouth that causes bleeding in the exposed worker. Splash of blood, visibly bloody fluid, or other potentially infectious material to a mucosal surface (mouth, nose, or eyes). A non-intact skin (e.g., dermatitis, chapped skin, abrasion, or open wound) exposure to blood, visibly bloody fluid, or other potentially infectious material.

  32. Source Patient Testing • Rapid HIV testing is recommended OSHA regulated organizations required to use rapid HIV testing • Specific (opt-in) informed consent is required • If HIV Ab test is positive, assume true positive until proven otherwise • If HIV Ab test is negative BUT SP may have had HIV exposure in the last 6 weeks, obtain HIV VL on SP and continue PEP until undetected VL • SP evaluation of risk for HIV exposure is key

  33. EP Baseline HIV Test Confidential baseline HIV testing of the exposed worker should be obtained at the time the occupational exposure is reported or within 3 days of the exposure. (AIII) Testing must be performed in full compliance with New York State Public Health Law A negative HIV test only demonstrates that the exposed worker was not previously infected with HIV before the exposure occurred; the baseline HIV test cannot determine whether the exposed worker was infected as a result of the exposure.

  34. Timing of PEP Initiation • When a potential occupational exposure to HIV occurs, every effort should be made to initiate PEP as soon as possible, ideally within 2 hours. (AII) • A first dose of PEP should be offered to the exposed worker while the evaluation is underway. • Decisions regarding initiation of PEP beyond 36 hours post exposure should be made on a case-by-case basis with the realization of diminished efficacy when timing of initiation is prolonged. (AII) • An absolute elapsed time after which PEP should not be administered cannot be stated with certainty.

  35. Preferred PEP Regimen Truvada [TRV] (tenofovir 300 mg/emtricitabine 200 mg) one tablet daily + Isentress (raltegravir [RAL]) 400 mg BID Duration X 28 days (or until SP ruled out for HIV)

  36. Alternative PEP Regimens TRV one tab + Darunavir (DRV) 800 mg OR Atazanavir (ATV) 300 mg OR Fosamprenavir (FPV) 1400 mg + Ritonavir (RTV) 100 mg All once daily TRV+ ZDV or TRV + Lopinavir/ritonavir (LPVr) or ZDV/3TC (Combivir) + one of the following RTV-boosted PIs: DRV, ATV, FPV, or LPV

  37. PEP in Pregnancy The recommended PEP regimen is the same for pregnant women as for non-pregnant adults (see Section VIII: Recommended PEP Regimen). (AII) Before administering PEP to a pregnant woman, the clinician should discuss the potential benefits and risks to her and to the fetus.

  38. PEP in Lactating EP • Both HIV and antiretroviral drugs may be found in breast milk • Initiation of PEP in exposed workers who are breastfeeding requires careful discussion • Clinicians should discuss the risks and benefits with the exposed worker. • Clinicians should advise women who may have been exposed to HIV through occupational exposure to avoid breastfeeding for 3 months after the exposure • If HIV infection is definitively excluded in SP at any time prior to 3 months postexposure, the woman may resume breastfeeding

  39. PEP Follow-Up Schedule

  40. Sequential HIV Testing HIV testing at 6 months post-exposure is no longer recommended HIV testing of the exposed worker at 4 weeks and 12 weeks should be performed with laboratory-based HIV tests rather than rapid point-of-care HIV tests If the post-exposure evaluation determined that PEP was indicated, but the exposed worker declines PEP, serial testing should still be obtained

  41. HCV Exposures- Baselines • Source Patient: • HCV antibody test (e.g., EIA/ELISA), and if positive, HCV RNA test or RIBA • Exposed Worker: • Liver panel including liver enzymes • HCV antibody, and if positive, HCV RNA test

  42. HCV Exposure Follow-Up • If the source patient is known to be positive for HCV antibody and/or HCV RNA, the follow-up schedule for the exposed worker should be as follows (AII): • Week 4: HCV RNA and liver panel • Week 12: HCV RNA and liver panel • Week 24: Liver panel and HCV antibody

  43. HCV Exposures

  44. 2. Exposure Management • Wash immediately w/ soap and water • Flush mucous membranes with water • No evidence use of antiseptics or expressing fluid reduces transmission • Antiseptics not indicated; caustic agents (bleach) not recommended • “Milking the wound” may increase risk • increases local inflammation

  45. 3. Source HIV Status • Source HIV status unknown • Voluntary HIV testing/informed consent • Document if source unwilling or unable to consent • Rapid HIV testing +/- HIV RNA recommended • OSHA regulations require rapid testing for occupational exposures • HIV RNA if recent potential HIV exposure to source • Rapid test result positive • Result to source; confirmed by HIV Western blot

  46. Source HIV Status • Obtain preexisting HIV test results • Obtain consent for release of HIV information, or • Contact source’s physician for documentation of results (patient consent not required) • If source HIV-, no PEP unless acute antiretroviral syndrome or recent HIV infection is suspected

  47. 3. Source HIV Status • Known HIV Infection • Stage of infection (early, late or end stage) • CD4, viral load testing, resistance testing • Current and previous antiretroviral therapy • Consider involvement of HIV Specialist • Don’t delay treatment of HCW waiting for results

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