Management of Occupational Exposures to HIV

1. 林口長庚醫院 內科部 感染醫學科 吳丁樹 醫師 Management of Occupational Exposures to HIV

2. 一位23歲林姓護士在照顧一位末期愛滋病人時不慎被IC針所刺傷食指一位23歲林姓護士在照顧一位末期愛滋病人時不慎被IC針所刺傷食指 • 請問如何處理? • 需要吃抗病毒藥物嗎? • 吃幾種藥物? • 吃多久?

3. Post-exposure prophylaxis (PEP) • Definitions • Exposures • Risks • Timing and duration of PEP • Selection of HIV PEP Regimens • Special issue in pregnancy • Follow-up • Post-contact seroconversion in HCWs • Infection control strategies

4. Definition • Health-care personnel (HCP) : all paid and unpaid persons working in health-care settings who have the potential for exposure to infectious materials (e.g., blood, tissue, and specific body fluids and medical supplies, equipment, or environmental surfaces contaminated with these substances).

5. Exposures • Percutaneous injury (e.g., a needlestick or cut with a sharp object) or • Contact of mucous membrane or nonintact skin (e.g., exposed skin that is chapped, abraded, or afflicted with dermatitis) with blood, tissue, or other body fluids that are potentially infectious. • Visibly bloody body fluids, semen and vaginal secretions also are considered potentially infectious

6. Exposures • Cerebrospinal fluid, synovial fluid, pleural fluid, peritoneal fluid, pericardial fluid, and amniotic fluid. The risk for transmission of HIV infection from these fluids is unknown. • Feces, nasal secretions, saliva, sputum, sweat, tears, urine, and vomitus are not considered potentially infectious unless they are visibly bloody.

7. Janeway’s Immunobiology 7/e

10. Risks • the average risk for HIV transmission after a percutaneous exposure to HIV-infected blood has been estimated to be approximately 0.3% • after a mucous membrane exposure, approximately 0.09% • larger quantity of blood • a device (e.g., a needle) visibly contaminated with the patient’s blood • a procedure that involved a needle being placed directly in a vein or artery • a deep injury • Terminal HIV-related illness in the source patient.

11. Controversy • lower viral load (e.g., <1,500 RNA copies/ mL) or one that is below the limits of detection probably indicates a lower titer exposure, it does not rule out the possibility of transmission

12. Timing and Duration of PEP • as soon as possible, preferably within hours rather than days of exposure • Because 4 weeks of ZDV appeared protective in occupational and animal studies, PEP should be administered for 4 weeks, if tolerated. • Reevaluation of exposed HCP should be strongly encouraged within 72 hours postexposure, especially as additional information about the exposure or source person becomes available.

13. Science. 1995 Nov 17;270(5239):1197-9. • Prevention of SIV Infection in Macaques by (R)-9-(2-Phosphonylmethoxypropyl)adenine • Che-Chung Tsai (1), Kathryn E. Follis, Alexander Sabo, Thomas W. Beck, Richard F. Grant, Norbert Bischofberger, Raoul E. Benveniste, Roberta Black • The efficacy of pre- and postexposure treatment with the antiviral compound (R)-9-(2-phosphonylmethoxypropyl)adenine (PMPA) was tested against simian immunodeficiency virus (SIV) in macaques as a model for human immunodeficiency virus (HIV). PMPA was administered subcutaneously once daily beginning either 48 hours before, 4 hours after, or 24 hours after virus inoculation. Treatment continued for 4 weeks and the virologic, immunologic, and clinical status of the macaques was monitored for up to 56 weeks. PMPA prevented SIV infection in all macaques without toxicity, whereas all control macaques became infected. These results suggest a potential role for PMPA prophylaxis against early HIV infection in cases of known exposure. Tenofovir

14. Selection of HIV PEP Regimens • 2 drugs or 3 drugs? • The main arguments in favour of two-drug PEP (fewer side effects, better adherence and course completion rates) are being addressed through switching to better-tolerated agents with lower pill burdens. • At the same time, a potent three-drug PEP regimen is preferred because resistance to antiretroviral drugs is found at significant levels in both treated and untreated infected individuals in the UK.

15. Selection of HIV PEP Regimens • the source of the occupational exposure (e.g., possible treatment history or antiretroviral drug resistance) • history of and response to antiretroviral therapy based on clinical response, CD4+ T-cell counts, viral load measurements, and current disease stage. • The addition of a third (or even a fourth) drug should be considered for exposures that pose an increased risk for transmission or that involve a source in whom antiretroviral drug resistance is likely.

16. Selection of HIV PEP Regimens Clin Infect Dis 2004;39:395–401

17. Determine the exposure code The Sanford Guide to HIV/AIDS Therapy 2010

18. Determine HIV status of exposure The Sanford Guide to HIV/AIDS Therapy 2010

19. Determine PEP Recommendation The Sanford Guide to HIV/AIDS Therapy 2010

20. HIV-positive, class 1 — asymptomatic HIV infection or known low viral load (e.g., <1,500 ribonucleic acid copies/mL). HIV-positive, class 2 — symptomatic HIV infection, acquired immunodeficiency syndrome, acute seroconversion, or known high viral load. ¶ For example, solid needle or superficial injury. §§ For example, large-bore hollow needle, deep puncture, visible blood on device, or needle used in patient’s artery or vein.

21. ** For example, a few drops. ¶¶ For example, a major blood splash.

23. Toxicity

24. Drug interactions

27. Drug resistance • hitherto undiagnosed; in this case, prevalence of resistance to any class of drug can be estimated as 5–10%; • already diagnosed, and untreated; these patients are increasingly likely to have had a resistance test undertaken, since baseline testing is recommended; • on treatment with undetectable viral load; they will be of very low infectivity, and will also probably have had a baseline resistance test; • on treatment with detectable viral load; they are likely to have resistant virus and also a recent resistance test.

28. Pregnancy • Urgent pregnancy testing should be arranged for any female worker who cannot rule out the possibility of pregnancy • should be counselled about the risks of HIV infection, about the risks for transmission to her baby, and about what is known and not known about the potential benefits and risks of antiretroviral therapy for her and her baby • drugs that may cause nausea may exacerbate pregnancy associated nausea • Efavirenz is contraindicated in pregnancy and not recommended for inclusion in PEP regimens • Indinavir (IDV) is associated with infrequent side effects in adults (i.e., hyperbilirubinemia and renal stones) that could be problematic for a newborn.

29. Follow-up • Extended HIV follow-up (e.g., for 12 months) is recommended for HCP who become infected with HCV after exposure to a source coinfected with HIV and HCV. Am J Med. 1997 May 19;102(5B):115-6.

30. 病人為 anti-HCV(+) 病人為 VDRL(+) TPHA1:80 病人為 anti-HIV(+) 員工抽血檢驗 anti-HCV 員工檢驗 anti-HIV， 視情況服用 抗愛滋藥物 員工本人為 HBsAg(+)或 anti-HBs(+)或 anti-HBc(+) 員工為 anti-HCV() 扎傷後一、 三、六個月 、一年追蹤 anti-HIV 不需注射 疫苗或HBIG 儘快注射HBIG 並接種疫苗 扎傷後半年、一年追蹤GOT, GPT, HBsAg, anti-HBs, anti-HBc等 員工污染性尖銳器械傷害後感染追蹤檢驗流程 發生被感染病人使用過之物品扎傷或割傷等情況 病人為 HBsAg(+) 員工為HBsAg(-)、 anti-HBs(-) 且未注射疫苗; 員工本人為HBsAg(-)、anti-HBs(-)已完成注射但未產生抗體 Penicillin 預防注射 扎傷後半年、一 年抽血檢驗anti- HCV, GOT, GPT

33. Clin Infect Dis 1999;28:365–83

34. Occupational HIV infection • The majority of documented infections occurred in nurses or clinical laboratory workers (66 of 94; 70.2%) after contact with infected blood (84 of 94; 89.4%) from a patient with with infected blood (84 of 94; 89.4%) from a patient with AIDS (40 of 52; 76.5%), by percutaneous exposure (83 of 94; 88.3%) during a procedure involving the placement of a device in an artery or vein (43 of 63; 68%). Clin Infect Dis 1999;28:365–83

35. Occupational HIV infection • Some job categories for which a high exposure risk has been demonstrated, such as midwives and surgeons. • Eighteen cases of documented HIV infection occurred despite PEP with zidovudine. • Four of these patients had a negative HIV test at 6 months following exposure. • However, testing the HCW again at 1 year post-exposure can be considered for additional reassurance. Clin Infect Dis 1999;28:365–83

36. Standard Precautions to Prevent HIV Transmission • Standard precautions (body substance isolation plus universal precautions) • core elements: • hand washing • barrier precautions • barrier precautions to prevent direct contact with all body fluids, except sweat, and tissues • minimal manual manipulation of sharp instruments and devices • disposal of these items in puncture-resistant containers

37. Other Measures to Prevent HIV Transmission • Personal protective barriers • gloves; gowns; goggles • Safety devices • blunt-tip suture needle • needleless systems • Work techniques • Sterilization and disinfection

38. References • Updated U.S. Public Health Service Guidelines for the Management of Occupational Exposures to HIV and Recommendations for Postexposure Prophylaxis MMWRSeptember 30, 2005 / Vol. 54 / No. RR-9 • HIV post-exposure prophylaxis: Guidance from the UK Chief Medical Officers’ Expert Advisory Group on AIDS, Sep, 2008, Department of Health, UK • Tsai CC, Follis KE, Sabo A, Beck TW, Grant RF, Bischofberger N, Benveniste RE, Black R. Prevention of SIV infection in macaques by (R)-9-(2-phosphonylmethoxypropyl)adenine. Science. 1995 Nov 17;270(5239):1197-9. • Bassett IV, Freedberg KA, Walensky RP. Two drugs or three? Balancing efficacy, toxicity, and resistance in postexposure prophylaxis for occupational exposure to HIV. Clin Infect Dis. 2004 Aug 1;39(3):395-401. Epub 2004 Jul 16. • Raphael J. Landovitz, and Judith S. Currier. Postexposure Prophylaxis for HIV Infection. N Engl J Med 2009;361:1768-75. • Cardo DM, Culver DH, Ciesielski CA, Srivastava PU, Marcus R, Abiteboul D, Heptonstall J, Ippolito G, Lot F, McKibben PS, Bell DM. 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 Nov 20;337(21):1485-90. • Giuseppe Ippolito, Vincenzo Puro, Julia Heptonstall, Janine Jagger, Gabriella De Carli, and Nicola Petrosillo. Occupational Human Immunodeficiency Virus Infection in Health Care Workers: Worldwide Cases Through September 1997. Clinical Infectious Diseases 1999;28:365–83.

39. Updateonhaart

41. Initiation of Antiretroviral Therapy • CD4 count < 350 cells/mm3 • Pregnancy, HIV-associated nephropathy, and hepatitis B virus (HBV) coinfection when treatment of HBV is indicated.

42. Preferred regimens • Efavirenz/tenofovir/emtricitabine; ritonavir-boosted atazanavir + tenofovir/emtricitabine; ritonavir-boosted darunavir + tenofovir/emtricitabine; and raltegravir + tenofovir/emtricitabine. • Lopinavir/ritonavir-based regimens are now listed as “Alternative” instead of “Preferred” regimens, except in pregnant women, where twice-daily lopinavir/ritonavir + zidovudine/lamivudine remains a “Preferred” regimen.

43. PLASMA HIV RNA TESTING • The minimal change in viral load considered to be statistically significant (2 standard deviations) is a threefold, or a 0.5 log10 copies/mL change. • One key goal of therapy is suppression of viral load to below the limits of detection (below 40–75 copies/mL by most commercially available assays). • For most individuals who are adherent to their antiretroviral regimens and who do not harbor resistance mutations to the prescribed drugs, viral suppression is generally achieved in 12–24 weeks, even though it may take a longer time in some patients.

44. CD4+ T-CELL COUNT • increase in CD4 count in the range of 50–150 cells/mm3 per year, generally with an accelerated response in the first 3 months. • increase of approximately 50–100 cells/mm3 per year. • Severely depleted CD4 count may have a blunted increase in their count despite virologic suppression.

45. Drug resistance testing • Genotypic testing is recommended as the preferred resistance testing to guide therapy in patients with suboptimal virologic responses or virologic failure while on first or second regimens • Addition of phenotypic testing to genotypic testing is generally preferred for persons with known or suspected complex drug resistance mutation patterns, particularly to protease inhibitors

46. Thank you for your attention!