HIV, HBV, AND HCV POSTEXPOSURE MANAGEMENT FOR HEALTHCARE WORKERS. Weerawat Manosuthi Bamrasnaradura Infectious Diseases Institute

Transcription

1 HIV, HBV, AND HCV POSTEXPOSURE MANAGEMENT FOR HEALTHCARE WORKERS Weerawat Manosuthi Bamrasnaradura Infectious Diseases Institute

2 Outline Case scenario of HIV postexposure prophylaxis Risks of and how to manage postexposure prophylaxis Current HIV PEP guideline US PHS 2013 New York guideline 2012 Thai guideline 2010 HBV and HCV postexposure mannagement

3

4 Case presentation 1 Male paramedic splashed with large volume of bloody amniotic fluid onto open ulcers on his arm. He has DM II, HT, DLP, GERD, CKD, peripheral neuropathy. Source is HIV+ without any treatment during this pregnancy. Paramedic started on AZT, 3TC, and lopinavir/rtv. Two days later, he complains of overwhelming nausea and vomiting.

5 Case 2: 32 Year-old Nurse 11 Jan 15: Her left finger got stuck with a needle #18 used to draw blood from a patient. Visibly bloody superficial stick was found. This source patient is a HIV-infected patient with a history of multiple ARV regimens (NRTIs, NNRTIs, PIs). Year Regimens Viral load RAMs 2001 d4t, 3TC, EFV VL < AZT, 3TC, EFV VL < AZT, 3TC, LPV/r VL 76,800 RT: 103N, 190A 2011 VL 99,500 RT: 103N, 138K 2013 TDF, 3TC, LPV/r VL 318,000 RT: 138A Nov 14 VL 519,000 She was admitted with pneumonia and MAC infection. Her current ARV regimen was TDF, 3TC, LPV/r. She had a recent history of virologic failure with HIV RNA of 519,000 copies/ml and genotypic resistance showed NNRTI RAMs without NRTIs and PIs.

6 AK , 32 Year-old Nurse 11 Jan 15: Her left finger got stuck with a needle #18 used to draw blood from a patient Visibly bloody AZT, 3TC, superficial EFV stick was VL <50 found. This source 2010 patient is AZT, a 3TC, HIV-infected LPV/r patient VL 76,800 with a history RT: of 103N, multiple 190A ARV regimens(nrtis, NNRTIs, PIs). Year Regimens Viral load RAMs 2001 d4t, 3TC, EFV VL < VL 99,500 RT: 103N, 138K He was 2013 admitted with TDF, pneumonia 3TC, LPV/r and MAC infection. VL 318,000 His current ARV RT: regimen 138A was TDF, 3TC, LPV/r. He had Nov a 14 recent history of virologic failure with VL HIV 519,000 RNA of 519,000 copies/ml and genotypic resistance showed NNRTI RAMs without NRTIs and PIs. What would you manage this expose person? Would you prescribe NRTI drugs in this expose person? 1. I would 2. I would not What third agent should be given?

7 AK , 32 Year-old Nurse 11 Jan 15: Her left finger got stuck with a needle #18 used to draw blood from a patient. Visibly bloody superficial stick was found. This source patient is a HIV-infected patient with a history of multiple ARV regimen (NRTIs, NNRTIs, PIs). She was admitted with pneumonia and MAC infection. Her current ARV regimen was TDF, 3TC, LPV/r. She had a recent history of virologic failure with HIV RNA of 519,000 copies/ml and genotypic resistance showed NNRTI RAMs without NRTIs and PIs. TDF/FTC, Raltegravir, DRV/r was given.

8 AK , 32 Year-old Nurse 22 Jan 15: She developed petechial rashes at trunk and extremities without fever. CBC showed HCT 40%, WBC 4,900, N56%, L34%, Mo7%, Eo2%, Ba1%, plt 210,000. ALT was 88U/L and Cr was 0.68 mg/dl. How to manage this event? A. Continue PEP regimen B. Discontinue PEP regimen C. Modify PEP regimen D. Others

9 AK , 32 Year-old Nurse 22 Jan 15: She developed petechial rashes at trunk and extremities without fever. CBC showed HCT 40%, WBC 4,900, N56%, L34%, Mo7%, Eo2%, Ba1%, plt 210,000. ALT was 88U/L and Cr was 0.68 mg/dl. How to manage this event?

10 Postexposure Prophylaxis Occupational exposure - Percutaneous exposure - Mucous membrane exposure - Non-intacted skin Non-occupational exposure - Sexual exposure - Intravenous drug user

11 Who is the most frequently reported occupational acquired HIV infection? 1. Nurses 2. Physicians 3. Lab technicians 4. House keepers

12 Occupational Acquired HIV infection Do A, et al. Infect Control Hosp Epidemiol 2003;24:86-96.

13 Accidental Injuries in BIDI On exposed person analysis, 7.5% (3 of 40), 2.9% (1 of 34), 0% were positive for HBsAg, Anti-HCV and Anti-HIV, respectively. Seven of 45 (15.5%) events were severe exposures. 24 % (22of 45) of staffs initiated HIV PEP. 16 % initiated within 1 hour after exposure and half of them continued HIV PEP until 4 weeks. 53% (24 of 45) of staffs had previous history of HBV vaccination.

14 Postexposure Management Step Management 1 Exposure site management 2 Exposure reporting 3 Evaluation of transmission risk 4 Counseling 5 Consideration of PEP 6 Follow-up

15 Exposure Site Management Wound and skin: washed with soap and water Mucous membrane: flushed with water No evidence of benefit for: Application of antiseptics or disinfectants Squeezing ( milking ) puncture sites Avoid use of bleach and other agents caustic to skin

16 Postexposure Management Step Management 1 Exposure site management 2 Exposure reporting (1-4) 3 Evaluation of transmission risk 4 Counseling 5 Consideration of PEP 6 Follow-up

17 Exposure Report 1 (1) Details of procedure being performed Date and time of exposure Where and how exposure occurred Type and brand of device How and when in course of handling device (2) Details of exposure Type and amount of fluid, severity of exposure Percutaneous: depth of injury whether fluid was injected Skin or mucous membrane: estimated volume of material, condition of skin

18 Exposure Report 2 (3) Details of exposure source Source of material contained HBV, HCV or HIV? If HIV-infected: stage of disease, history of ARV, viral load, ARV resistance (4) Details of exposed person Anti HIV, Anti HBV, Anti HCV status Hepatitis B vaccination & vaccine response

19 Postexposure Management Step Management 1 Exposure site management 2 Exposure reporting 3 Evaluation of transmission risk 4 Counseling 5 Consideration of PEP 6 Follow-up

20 Evaluation of Transmission Risk 3 Type of HIV transmission Risk of transmission per exposure event Blood transfusion 0.95 Perinatal exposure 0.13 Needle stick (0.3%, 95%CI %) Unprotected receptive anal intercourse Needle sharing Unprotected receptive vaginal intercourse Mucous membrane exposure (0.09%, 95%CI %) Unprotected insertive vaginal intercourse Ingestion of human milk

21 Blood Potential fluid Body fluid containing visible blood CSF Pleural fluid Semen, Vg secretion Synovial fluid Pleural fluid Peritoneal fluid Non Potential fluid Feces Sweat Nasal secretion Tears Saliva Urine Sputum Vomitus Pericardial fluid Amniotic fluid Human bite Direct contact

22 Factors APPENDIX D. Associated LOGISTIC REGRESSION with ANALYSIS Transmission OF RISK FACTORS FOR HIV after INFECTION AFTER PERCUTANEOUS EXPOSURE TO HIV-INFECTED BLOOD Percutaneous Exposure Logistic Regression Analysis of Risk Factors for HIV Infection After Percutaneous Exposure to HIV-Infected Blood Risk Factor US Cases a All Cases b Adjusted odds ratio (95% CI) c Deep injury 16.1 ( ) Visible blood on device 5.2 ( ) Procedure involving needle in artery or vein 5.1 ( ) Terminal illness in source patient d 6.4 ( ) Postexposure use of zidovudine 0.2 ( ) Reprinted from Cardo DM, Culver DH, Ciesielski CA, et al. A case-control study of HIV seroconversion in health care workers after percutaneous exposure: Centers for Disease Control and Prevention Needlestick Surveillance Group. N Engl J Med 1997;337: [PubMed] a All risk factors were significant (P < 0.02). b All risk factors were significant (P < 0.01). c Odds ratios are for the odds of seroconversion after exposure in workers with the risk factor as compared with those without it. d Terminal illness was defined as disease leading to the death of the source patient from AIDS within two months after the health care worker s exposure. NEJM 1997; 337: Postgrad Med J 2003,79:324-8.

23 Average Risk for Transmission of HIV, HBV, and HCV after Needle stick Source Risk HBV HBeAg+ HBeAg- 22.0% % 1.0% - 6.0% HCV+ 1.8% HIV+ 0.3%

24 Postexposure Management Step Management 1 Exposure site management 2 Exposure reporting 3 Evaluation of transmission risk 4 Counseling 5 Consideration of PEP 6 Follow-up

25 HIV Postexposure Counseling 1. Possible side effects of PEP drugs 2. Possible drug interactions 3. Adherence 4. Signs and symptoms of acute HIV infection Fever, rash, flu-like illness 5. Prevention of secondary transmission Sexual abstinence or condom use No blood/tissue donation Transmission and PEP drug risks if breastfeeding No work restriction indicated

26

27 Postexposure Management Step Management 1 Exposure site management 2 Exposure reporting 3 Evaluation of transmission risk 4 Counseling 5 Consideration of PEP 6 Follow-up

28 Considerations When Using PEP Risk of Transmission PEP Risk of Adverse Effects

29 Initiation of HIV PEP If indicated, start PEP as soon as possible after exposure Regard as an urgent medical concern Hours rather than days Interval after which PEP is no longer likely to be effective in humans is unknown Initiating PEP days or weeks after an exposure might be considered if warranted for increased risk exposure

30

31 Animal Studies of PEP: Prevention of SIV in macaques with Tenofovir 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 Tsai et al, J Virol 1998;72:4265.

32 Thai Guideline 2010 Prefered basic regimens Alternative basic regimens Expanded regimens AZT/3TC d4t/3tc PI: LPV/r, IDV/r, ATV/r, SQV/r TDF/3TC ddi/3tc NNRTI: EFV TDF/FTC Thai Guideline 2014 ส ตรยาต านไวร ส A TDF + 3TC/FTC + Lopinavir/r หมายเหต B C TDF + 3TC/FTC + Rilpivirine TDF + 3TC/FTC + Atazanavir/r TDF +3TC/FTC + Raltegravir ปร กษาแพทย ผ เช ยวชาญด านโรคต ดเช อก อนเร มยา AZT แทน TDF ในส ตร A หร อ B ในบ คลากรท ม GFR < 60

33

34 Figure 1. PEP Following Occupational Exposure Two-drug regimen is not recommended. New York Guideline

35 Recommended Regimen for HIV PEP Table 3 Recommended Regimen for HIV PEP Following Occupational Exposure a Tenofovir b 300 mg PO qd + Emtricitabine b,c 200 mg PO qd Plus AZT is no longer recommended. Raltegravir d 400 mg PO bid a When the source is known to be HIV-infected, past and current ART experience, viral load data, and genotypic or phenotypic resistance data (if available) may indicate the use of an alternative PEP regimen. Consult with a clinician experienced in managing PEP. See Tables 4 and 5. b The dosing of tenofovir and emtricitabine/lamivudine should be adjusted in patients with baseline creatinine clearance <50 ml/min (see Appendix A for dosing recommendations). Tenofovir should be used with caution in exposed workers with renal insufficiency or who are taking concomitant nephrotoxic medications. Fixed-dose combinations should not be used in patients who need dose adjustment due to renal failure. c Lamivudine 300 mg PO qd may be substituted for emtricitabine. However, a fixed-dose combination is available when tenofovir is used with emtricitabine (Truvada 1 PO qd). d The dosing of raltegravir should be adjusted when co-administered with rifampin (see Appendix A for dosing recommendations). A. Duration of PEP Regimen New York Guideline

36 Preferred Alternative PEP Regimens New York Guideline

37 Antiretroviral Drugs to Avoid Drugs to avoid Efavirenz Nevirapine Abacavir Stavudine and Didanosine Nelfinavir and Indinavir CCR5 co-receptor antagonists Reasons - CNS side effects are common - Complicating the need to provide a first dose at any time of the day - Should be avoided in pregnant women - Substantial efavirenz resistance - Severe hepatotoxicity - Hypersensitivity reactions - Possibility of toxicities -Poorly tolerated - Lack of activity against potential CXCR4 tropic virus New York Guideline

38 US PHS Guideline 2013 Infection Control Hospital Epidimiology 2013;34:

39 US PHS Guideline 2013 Infection Control Hospital Epidimiology 2013;34:

40 US PHS Guideline 2013 Infection Control Hospital Epidimiology 2013;34:

41 Drug-drug Interactions!

42 Drug-drug interactions

43 Consideration of PEP PEP during pregnancy Efavirenz is NOT recommended during pregnancy because of possible teratogenicity? Cases of fatal lactic acidosis in pregnant women treated with d4t and ddi reported Indinavir should not be given shortly before delivery because of hyperbilirubinemia

44

45 Primary HIV Infection: Common Signs & Symptoms fever 86 lethargy 74 myalgias rash headache pharyngitis adenopathy N = 160 patients with PHI in Geneva, Seattle and Sydney % of patients Vanhems P et al. AIDS 2000; 14:

46 Primary HIV Infection: Other Signs & Symptoms aseptic meningitis 24 oral ulcers 15 genital ulcers 10 thrombocytopenia 45 leukopenia 40 transaminitis % of patients Kahn JO, Walker BD. N Engl J Med. 1998;339:33-39.

47 Postexposure Management Exposure site management Exposure reporting Evaluation of transmission risk Counseling Consideration of PEP Follow-up

48 New York 2012: How to Follow-up New York Guideline

49 US PHS 2013: How to Follow-up Infection Control Hospital Epidimiology 2013;34:

50 Thai 2014: How to Follow-up

51 Postexposure Management Step Management 1 Exposure site management 2 Exposure reporting 3 Evaluation of transmission risk 4 Counseling 5 Consideration of PEP 6 Follow-up

52 Summary of PEP Recommendation Thai 2014 US PHS 2013 New York 2012 Time to initiate PEP < 72 hrs ASAP, <72 hrs Prefer <2 hrs, < 36 hrs Preferred PEP Alternative PEP LPV/r ATV/r RPV RAL EFV TDF/FTC TDF /3TC AZT/3TC RAL TDF/FTC RAL TDF/FTC RAL DRV/r ATV/r LPV/r ETR RPV TDF/FTC TDF/3TC AZT/3TC AZT/FTC DRV/r ATV/r FPV/r TDF/FTC

53 Summary of HIV Test Recommendation Baseline Wk 4 Wk 6 Wk 12 Wk 16 Wk 24 Wk 48 US PHS 2013* X X X X* X** New York 2012 X X X X** Thai 2014 X X X X** WHO 2007 X X X X** *Only wk 0, 6, 16 if use 4 th gen combination HIV p24 Ag-HIV Ab test **In case of HCV co-infection

54 Occupational exposure to HBV

55 HBV and HCV Transmission Risk after Needle stick Compared to HIV Source Risk HBV HBeAg+ HBeAg- 22.0% % 1.0% - 6.0% HCV+ 1.8% HIV+ 0.3%

56 HBV Postexposure Management Management depends on: Source hepatitis B surface antigen status Whether exposed person vaccinated Whether exposed person has immunity

57 Recommended PEP for Exposure to HBV Vaccination and Ab response status of exposed workers Source HBs Ag positive Treatment Source HBs Ag negative Source unknown or not available for testing Unvaccinated/Nonimmune HBIG 1 and initiate HB vaccine series Initiate HB vaccine series Initiate HB vaccine series Previously vaccinated - Known responder No treatment No treatment No treatment - Known nonresponder HBIG 0.06 ml/kg IM HBIG 1 and initiate revaccination or HBIG 2 No treatment If known high risk source, treat as if source were HBsAg+

58 Recommended PEP for Exposure to HBV Vaccination and Ab response status of exposed workers Previously vaccinated but Ab response unknown Source HBs Ag positive Treatment Source HBs Ag negative Source unknown or not available for testing Single vaccine dose No treatment No treatment unless high-risk source; if high-risk source, treat as if source were HBsAg positive If still undergoing vaccination HBIG 1; complete series Complete series Complete series

59 Efficacy of HBV PEP Regimen Multiple doses of HBIG alone when 1st dose initiated within 1 week Hepatitis B vaccine series alone Combination of HBIG and vaccine series * Estimated for adults, based on perinatal data Prevention of HBV Infection 70-75% 70-75% 85-95% MMWR Recomm Rep. 2003;52(RR-01):1-36. BeasleyRP, et al. Hepatology. 1983;3:

60 Follow-up HBV Testing of Exposed Person Perform follow-up anti-hbs testing in healthcare personnel who receive hepatitis B vaccine Test for anti-hbs 1-2 months after last dose Anti-HBs response to vaccine cannot be ascertained if HBIG received in the previous 3-4 months

61 Occupational exposure to HCV

62 Occupational Transmission of HCV Inefficiently transmitted by occupational exposures Average incidence 1.8% (range 0-7%) following percutaneous exposure from HCV-positive source Case reports of transmission from blood splash to mucous membrane Prevalence 1-2% among healthcare personnel Lower than among adults in the general population 10 times lower than for HBV infection

63 Interpretation of Hepatitis C Test Anti-HCV screening test results (EIA) HCV RNA (PCR) Nonreactive Nonreactive Not infected with HCV Comments Nonreactive Positive Active HCV infection; test subject is likely immune compromised. Reactive Negative 1. Resolved infection 2. Active infection. Single negative HCV RNA result does not rule out active infection. Follow-up HCV RNA test needed in > 6 months 3. False positive EIA test Reactive Positive Active HCV infection. Adapted from MMWR 2003;52(No. RR-3):11.

64 Hepatitis C Post-Exposure Management According to Baseline Test Results Clinical Scenario Source patient: HCV-antibody - neg Source patient: Unavailable or refuses testing Source patient: HCV-antibody - pos and HCV RNA - neg (A single negative HCV RNA result does not exclude active infection) Source patient: Both HCV antibody and HCV RNA - pos and Exposed worker is HCV-antibody negative Exposed worker: Both HCV antibody and HCV RNA - pos Follow-Up No further testing or follow-up is necessary for source patient or the exposed worker Exposed worker: Follow-up HCV antibody at 3 and 6 months Manage the exposed worker as if the source patient has chronic hepatitis C Source patient: Counsel and manage as chronic hepatitis C regardless of status of exposed worker Exposed worker: Follow up as outlined in Post-Exposure Follow-Up for HCV Counsel and manage as chronic hepatitis C

65 Postexposure Prophylaxis and Follow-up for HCV Not recommended after exposure immunoglobulin not effective no data on use of antivirals (e.g., interferon), and may be effective only with established infection antivirals not FDA approved for this setting For individuals exposed to hepatitis C-infected source patients Follow-up with HCV RNA is recommended in addition to HCV antibody testing Because HCV RNA testing can identify acute infection within 2 weeks of exposure Antibody test can be delayed up to several months after acute infection % Seroconversion with ELISA antibody Time after exposure 50% 9 weeks 80% 15 weeks 97% 6 months

66 Follow-up of HCV-Exposed HCP HCV Ab LFT HCV RNA Baseline (source HCV+ or unknown) X X 1 month X If source HCV + 3 months X X X 6 months X X X Increase in ALT in 1st 24 wks X

67 Case presentation 1 Male paramedic splashed with large volume of bloody amniotic fluid onto open ulcers on his arm. He has DM II, HT, DLP, GERD, CKD, peripheral neuropathy. Source is HIV+ without any treatment during this pregnancy. Paramedic started on AZT, 3TC, and lopinavir/rtv. Two days later, he complains of overwhelming nausea and vomiting.

68 Case 2: 32 Year-old Nurse 11 Jan 15: Her left finger got stuck with a needle #18 used to draw blood from a patient. Visibly bloody superficial stick was found. This source patient is a HIV-infected patient with a history of multiple ARV regimens (NRTIs, NNRTIs, PIs). Year Regimens Viral load RAMs 2001 d4t, 3TC, EFV VL < AZT, 3TC, EFV VL < AZT, 3TC, LPV/r VL 76,800 RT: 103N, 190A 2011 VL 99,500 RT: 103N, 138K 2013 TDF, 3TC, LPV/r VL 318,000 RT: 138A Nov 14 VL 519,000 She was admitted with pneumonia and MAC infection. Her current ARV regimen was TDF, 3TC, LPV/r. She had a recent history of virologic failure with HIV RNA of 519,000 copies/ml and genotypic resistance showed NNRTI RAMs without NRTIs and PIs.

69 AK , 32 Year-old Nurse 11 Jan 15: Her left finger got stuck with a needle #18 used to draw blood from a patient Visibly bloody AZT, 3TC, superficial EFV stick was VL <50 found. This source 2010 patient is AZT, a 3TC, HIV-infected LPV/r patient VL 76,800 with a history RT: of 103N, multiple 190A ARV regimens(nrtis, NNRTIs, PIs). Year Regimens Viral load RAMs 2001 d4t, 3TC, EFV VL < VL 99,500 RT: 103N, 138K He was 2013 admitted with TDF, pneumonia 3TC, LPV/r and MAC infection. VL 318,000 His current ARV RT: regimen 138A was TDF, 3TC, LPV/r. He had Nov a 14 recent history of virologic failure with VL HIV 519,000 RNA of 519,000 copies/ml and genotypic resistance showed NNRTI RAMs without NRTIs and PIs. What would you manage this expose person? Would you prescribe NRTI drugs in this expose person? 1. I would 2. I would not What third agent should be given?

70 AK , 32 Year-old Nurse 11 Jan 15: Her left finger got stuck with a needle #18 used to draw blood from a patient. Visibly bloody superficial stick was found. This source patient is a HIV-infected patient with a history of multiple ARV regimen (NRTIs, NNRTIs, PIs). She was admitted with pneumonia and MAC infection. Her current ARV regimen was TDF, 3TC, LPV/r. She had a recent history of virologic failure with HIV RNA of 519,000 copies/ml and genotypic resistance showed NNRTI RAMs without NRTIs and PIs. TDF/FTC, Raltegravir, DRV/r was given.

71 AK , 32 Year-old Nurse 22 Jan 15: She developed petechial rashes at trunk and extremities without fever. CBC showed HCT 40%, WBC 4,900, N56%, L34%, Mo7%, Eo2%, Ba1%, plt 210,000. ALT was 88U/L and Cr was 0.68 mg/dl. How to manage this event? A. Continue PEP regimen B. Discontinue PEP regimen C. Modify PEP regimen D. Others

72 AK , 32 Year-old Nurse 22 Jan 15: She developed petechial rashes at trunk and extremities without fever. CBC showed HCT 40%, WBC 4,900, N56%, L34%, Mo7%, Eo2%, Ba1%, plt 210,000. ALT was 88U/L and Cr was 0.68 mg/dl. How to manage this event?

73 Outline Case scenario of HIV postexposure prophylaxis Risks of and how to manage postexposure prophylaxis Current HIV PEP guideline US PHS 2013 New York guideline 2012 Thai guideline 2010 HBV and HCV postexposure mannagement

74 THANK YOU