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

2. 24/7 NYS PEP Line 888-448-4911

3. NYS PEP/AIDS Widget To Download Widget visit www.ceitraining.org

4. Overview HIV Post-Exposure Prophylaxis (PEP) HIV Post-Exposure Prophylaxis (PEP) oPEP (occupational PEP) oPEP (occupational PEP) nPEP (non-occupational PEP) nPEP (non-occupational PEP) Background Background Guidelines Guidelines Hepatitis B and C post-exposure protocols Hepatitis B and C post-exposure protocols

5. NON-OCCUPATIONAL PEP (nPEP)

6. nPEP Buy in from institution and staffs Establish protocol and policies Have first dose available to patient immediately Educate Staff on follow up Include Mental Health and SW

7. Non-Occupational Estimated Transmission Risk 1 Exposure Type if Source HIV infected Estimated Risk of Single Exposure Needle-sharing 0.67% (1/150) Receptive anal intercourse 0.5%-3% (1/200-6/200) Receptive vaginal intercourse 0.1% (1/1000) Insertive anal intercourse 0.065% (1/1500) Insertive vaginal intercourse 0.05% (1/2000) Receptive oral sex with ejaculation 0.005-0.01% 1 Hivguidelines.org

8. Cohen, JID, 2005 Probability of male-to-female HIV transmission per coital act, as a function of HIV disease stage in the index case

9. Support for PEP Treatment Guidelines Clearly identified risk factors for HIV transmission Clearly identified risk factors for HIV transmission ACTG 076 Study ACTG 076 Study Decreased perinatal transmission by 67% Decreased perinatal transmission by 67% CDC International Case Control Study CDC International Case Control Study Knowledge of pathogenesis of HIV seroconversion Knowledge of pathogenesis of HIV seroconversion Laboratory and animal models Laboratory and animal models No adequate human data on nPEP efficacy No adequate human data on nPEP efficacy

11. Risk Factors for HIV Transmission CDC Case Control Study - 1995 Risk Factors for HIV Transmission CDC Case Control Study - 1995 Risk FactorAdjusted Odds Ratio (95% CI) Deep Injury15 (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) AZT (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)

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

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

14. Key Elements 1. Assess Risk 2. Manage Exposure 3. Determine HIV Status of source, when possible 4. Dispense PEP if indicated 5. Educate and Counsel Exposed Patient 6. Documentation

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

16. 1.Assess Risk: Blood or Body Fluid Fluids with Risk: Blood or visibly bloody fluid Blood or visibly bloody fluid Semen Semen Vaginal secretions Vaginal secretions Cerebrospinal fluid Cerebrospinal fluid Synovial fluid Synovial fluid Pleural fluid Pleural fluid Pericardial fluid Pericardial fluid Amniotic fluid Amniotic fluid

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

18. 1.Assess Risk, cont. Non-risky Fluids* Saliva, sputum or nasal secretions Saliva, sputum or nasal secretions Tears Tears Sweat Sweat Urine Urine Stool Stool Emesis Emesis * Unless there is visible blood

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

20. PEP of Non-Occupational Exposures PEP recommended if source HIV+, high-risk, unknown (e.g. sexual assault) PEP NOT recommended  Unprotected vaginal/anal intercourse (receptive or insertive)  Unprotected receptive penile- oral contact with ejaculation  Oral-vaginal contact with blood exposure  Needle-sharing  Injury with blood exposure  needlestick, bite, accident  Kissing, or oral-oral contact & no mucosal damage  Bites without blood  Needles/sharps exposure not in contact with HIV + or at-risk person  Mutual masturbation – intact skin  Oral-anal contact  Receptive penile-oral contact without ejaculation  Insertive penile-oral contact  Oral-vaginal – no blood exposure Hivguidelines.org

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

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

23. 3.Source HIV Status Obtain preexisting HIV test results Obtain preexisting HIV test results Obtain consent for release of HIV information, or Obtain consent for release of HIV information, or Contact source’s physician for documentation of results (patient consent not required) Contact source’s physician for documentation of results (patient consent not required) If source known HIV-, no PEP If source known HIV-, no PEP Consider HIV RNA viral load testing to rule out acute HIV infection Consider HIV RNA viral load testing to rule out acute HIV infection

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

25. Risk Behavior PEP recommended PEP recommended Isolated exposure (sexual, needle, trauma) Isolated exposure (sexual, needle, trauma) Lapse in risk-reduction practices Lapse in risk-reduction practices Interest in behavioral change Interest in behavioral change Repeated high-risk behavior or presentation for repeat courses of PEP Repeated high-risk behavior or presentation for repeat courses of PEP Intensify education & prevention Intensify education & prevention Behavioral change Behavioral change

26. 4. PEP Recommendations NYS DOH Guidelines PEP ASAP, ideally within 2 hrs, no later than 36 hrs from exposure PEP ASAP, ideally within 2 hrs, no later than 36 hrs from exposure HAART (3 antiretroviral drugs) x 4 weeks HAART (3 antiretroviral drugs) x 4 weeks Baseline HIV serology of exposed person within 72 hours of initiating PEP Baseline HIV serology of exposed person within 72 hours of initiating PEP HIV specialist follow-up within 72 hours HIV specialist follow-up within 72 hours

27. 4. PEP Recommendations Beyond 36 Hours? “Decisions regarding initiation of nPEP beyond 36 hours post exposure should be made by the clinician in conjunction with the patient with the realization of diminished potential for success when timing of initiation is prolonged” 1 “Decisions regarding initiation of nPEP beyond 36 hours post exposure should be made by the clinician in conjunction with the patient with the realization of diminished potential for success when timing of initiation is prolonged” 1 Consider likelihood of HIV transmission Consider likelihood of HIV transmission http://hivguidelines.org/GuideLine.aspx?pageID=78&guideLineID=2

28. 4. PEP Recommendations Selection of HIV PEP Regimen PEP regimen usually empiric PEP regimen usually empiric If source known HIV+: If source known HIV+: consider HIV resistance consider HIV resistance genotype/phenotype/past antiretroviral drug history genotype/phenotype/past antiretroviral drug history

29. NYS: Preferred PEP Regimen Zidovudine (AZT) 300 mg po bid Lamivudine (3TC) 150 mg po bid PLUS Tenofovir 300 mg po daily with food OR Zidovudine 300 mg po bid PLUS Tenofovir 300 mg PO qd Emtricitabine 200mg po qd Combivir 1 po bid Truvada 1 po qd May substitute stavudine for AZT, nelfinavir or lopinavir for tenofovir; dosing by weight in children

30. 4. PEP Recommendations CDC: Basic HIV PEP Regimen zidovudine (ZDV) + lamivudine (3TC) or emtricitabine (FTC) zidovudine (ZDV) + lamivudine (3TC) or emtricitabine (FTC) ZDV 300 mg BID; 3TC 300 QD or 150 BID; FTC 200 QD ZDV 300 mg BID; 3TC 300 QD or 150 BID; FTC 200 QD tenofovir (TNF) + lamivudine (3TC) or emtricitabine (FTC) tenofovir (TNF) + lamivudine (3TC) or emtricitabine (FTC) TNF 300 mg QD/ / 3TC 300 QD or 150 BID; FTC 200 QD TNF 300 mg QD/ / 3TC 300 QD or 150 BID; FTC 200 QD

31. 4. PEP Recommendations CDC: Preferred Expanded PEP Regimen Basic regimen Basic regimenplus lopinavir/ritonavir (LPV/RTV) (or efavirenz [nPEP] lopinavir/ritonavir (LPV/RTV) (or efavirenz [nPEP] LPV/RTV: 400/100 mg = 2 tablets twice daily with food LPV/RTV: 400/100 mg = 2 tablets twice daily with food

32. 5. Education and Counseling Explain to patient: Potential exposure risk Potential exposure risk Risks and benefits of PEP Risks and benefits of PEP To report signs and symptoms of acute (primary) HIV infection To report signs and symptoms of acute (primary) HIV infection Prevention of secondary transmissions Prevention of secondary transmissions Acknowledge fear/anxiety commonly encountered by exposed health care workers and offer counseling services Acknowledge fear/anxiety commonly encountered by exposed health care workers and offer counseling services

33. Medication Side Effects Nausea Nausea Vomiting Vomiting Fatigue Fatigue Headache Headache Loss of appetite Loss of appetite Diarrhea Diarrhea Emperically give ant-emetic like Reglan and anti-diarrheal Immodium

34. 5. More Education and Counseling What prescribed person needs to know: What prescribed person needs to know: Knowledge about efficacy of PEP is limited Knowledge about efficacy of PEP is limited ZDV best shown to prevent HIV transmission in humans ZDV best shown to prevent HIV transmission in humans No data on combination therapy, but experts recommend multiple drugs to increase potency and overcome potential drug-resistant virus No data on combination therapy, but experts recommend multiple drugs to increase potency and overcome potential drug-resistant virus Any or all drugs for PEP may be declined by the HCW Any or all drugs for PEP may be declined by the HCW

35. 6. PEP Follow-up Monitoring Recommendations After Initiation of PEP (www.hivguidelines.org) www.hivguidelines.org VisitCBC/diffMet/LFT HIV Ab* BaselineXXXX Week 1 X Week 2 XX Week 3 X Month 1 XX Month 3 X Month 6 (X) Pregnancy test at baseline; * Recommended even if PEP is declined; optional if PEP not indicated; Follow-up by HIV Specialist recommended; monitor for acute retroviral syndrome

36. Longitudinal Care Recommend barrier protection for 3-6 months, while monitoring for PEP is ongoing Recommend barrier protection for 3-6 months, while monitoring for PEP is ongoing Avoid breastfeeding for 3-6 months Avoid breastfeeding for 3-6 months Women preferring to breastfeed between 3-6 months should carefully weigh risks/benefits Women preferring to breastfeed between 3-6 months should carefully weigh risks/benefits

37. AIDS 2001;1593:430, Arch Int Med 1999;159:2361-3 Failure of Post-Exposure Prophylaxis Failure documented with zidovudine (AZT; Retrovir) monotherapy and with combination therapies Failure documented with zidovudine (AZT; Retrovir) monotherapy and with combination therapies Potential explanations: Potential explanations: Viral resistance Viral resistance Large inoculum Large inoculum Delay in PEP Delay in PEP Lack of adherence to PEP Lack of adherence to PEP Infection at a time other than the known potential exposure Infection at a time other than the known potential exposure

38. . Occupational Blood-borne Exposures Relative Risk of Seroconversion with Percutaneous Injury From: CDC. MMWR 2001;50 (RR11):1-42.

39. Hepatitis B Management depends on: Management depends on: Source hepatitis B surface antigen status Source hepatitis B surface antigen status Whether exposed person vaccinated Whether exposed person vaccinated Whether exposed person has immunity Whether exposed person has immunity

40. Recommended PEP for Hepatitis B Virus Vaccination/Ab response status of exposed patient Treatment when source patient is: HBsAg positive HBsAg negative Source unknown or not available for testing Unvaccinated/ non-immune HBIG ×1; initiate HB vaccine series Initiate HB vaccine series Previously vaccinated, known responder No treatment Previously vaccinated, known non-responder HBIG ×1 and initiate revaccination or HBIG ×2 No treatmentNo treatment unless high-risk source; if high-risk source, treat as if source were HBsAg positive Previously vaccinated, response unknown Single vaccine booster dose No treatmentNo treatment unless high-risk source; if high-risk source, treat as if source were HBsAg positive Still undergoing vaccinated HBIG ×1; complete series Complete series

41. Hepatitis C No vaccine or treatment will prevent infection No vaccine or treatment will prevent infection Immune globulin not recommended; does not work Immune globulin not recommended; does not work Early infection effectively treated with Peg-interferon +/- ribavirin Early infection effectively treated with Peg-interferon +/- ribavirin

42. Exposure to Hepatitis C HCV Ab LFTS HCV RNA Baseline (source HCV+ or unknown) XX 1 month X If source HCV + X 3 months XXX 6 months XX Increase in ALT in 1st 24 wks X

43. nPEP Case JW, 21 year old WM presents to CCC, West Village on 7/15/10 for PEP. Reports going on- line and finding about PEP through www.pep411.com www.pep411.com Unprotected receptive anal sex with multiple partners the prior night Last tested HIV -, 2 weeks ago in St. Louis, MO First dose of PEP given in clinic within 32 hours of exposure

44. nPEP Case History of poly-substance abuse starting at age 16 Cocaine, crystal meth (now reports IV use for last 4-6 months) SW visit Unemployed, moved to NYC to get away from drug scene Referred to drug treatment programs (Realization Center, Andres Hoyas at Center) Assisted in applying for Medicaid, food stamps and Waverly Job Center

45. nPEP Case Baseline rapid HIV test negative Labs: CBC normal, LFT’s normal F/U 2 weeks: exam WNL, reports good tolerability and 100% adherence. No symptoms Misses 2 appts with SW and PCP 30 day rapid antibody negative. HIV viral load detectable at 96 copies

46. nPEP Case PE reveals exudative pharyngitis (L tonsil) Repeat Labs are Drawn: DNA PCR: 690 copies HIV Elisa and WB are positive