1. PRE AND POST EXPOSURE PROPHYLAXIS IN HIV PREVENTION Kimberly Woodhull, PharmD, AAHIVP

2. Objectives  Understand the current guidelines for occupational exposure prophylaxis  Select the appropriate drug regimen and duration of treatment for post exposure prophylaxis (PEP)  Understand the need for pre-exposure prophylaxis (PrEP)  Identify patients that are eligible for PrEP and recommend treatment

3. HIV Facts  In 2008, 2.7 million new HIV infections diagnosed worldwide  1.2 million people in US with HIV  21% unaware of their status  56,000 new HIV infections in US per year  Men who have sex with men (MSM) over half of new infections  Women 27% of new infections  HIV patients will spend $600,000 for lifetime care

4. AIDS Facts  In 2009, estimated 34,247 people were diagnosed with AIDS  More than 594,500 people have died of AIDS since beginning of epidemic  ~17,000 people died of AIDS in the US in 2009

5. Post Exposure Prophylaxis (PEP)

6. Percutaneous Occupational Exposures  In 2004, estimated 385,000 needlesticks/year  40-70% needlestick injuries unreported  Risk of Transmission  HIV- 0.3%  HBV-2-40%  HCV-2.7-10%  PEP 80% effective

7. Case –Is JR Candidate for PEP?  28 yo nurse assistant at elementary school  Stuck with needle while giving 3 rd grader a diabetes shot before lunch  Parents refusing HIV testing  Is JR candidate for PEP?

8. After Needle Stick Injury  Decontamination  Wash the area with soap and water  Avoid squeezing or milking the wound  Do not use caustic agents, such as bleach  Determine Risk  Type of exposure  Infection Status of Source  Decide on Treatment  Gets Labs and Follow up in 3-6 months

9. Post Exposure Prophylaxis for the Healthcare Worker  Percutaneous injury (needlestick, cut) OR  Contact of mucous membrane or nonintact skin  Blood  Tissue  Other body fluids that are potentially infectious (cerebrospinal, semen or vaginal secretions) Risks:With:

10. Assess Risk for HIV Infection  Type of exposure  Less severe: solid needle or superficial injury  More severe: large-bore hollow needle, deep puncture, visible blood on device, needle used in patient’s artery or vein  Infection status of source  Class 1: asymptomatic HIV infection or known low viral load (<1,500 copies/mL)  Class 2: symptomatic HIV, AIDS, acute seroconversion, or known high viral load

11. Initiating PEP  Start within 72 hours  2-3 drug regimen based on risk  PEP should be given for 28 days, if tolerated

12. PEP for Percutaneous Injuries HIV + Source Exposure TypeInfection Status of Source Exposure TypeInfection Status ofSource HIV+, class 1HIV+, class 2 Less severeRecommend basic 2-drug PEP Recommend expanded ≥3- drug PEP More severeRecommend expanded 3- drug PEP Recommend expanded ≥3- drug PEP

13. PEP for Percutaneous Injuries Unknown Source Exposure TypeInfection Status of Source Exposure TypeInfection Status ofSource Unknown HIV status* Unknown source Less severe Generally, no PEP warranted; consider basic 2- drug PEP if source has HIV risk factors Generally, no PEP warranted; consider basic 2- drug PEP if exposure to HIV- infected persons is likely More severeAs above *If PEP started and source later determined to be HIV negative, PEP should be discontinued.

14. Case –Is JR Candidate for PEP?  Exposure-Less severe  Infection source status-Unknown  Time –Within 72 hours  Treat?

15. However….  ER provider recommended starting PEP for 28 days:  Zidovudine/lamivudine (Combivir®)  Indinavir (Crixivan®) or Nevirapine (Viramune®)

16. Guidelines for Treatment  Basic 2 Drug Regimens:  Preferred: ZDV + 3TC or FTC TDF + 3TC or FTC  Alternative: d4T + 3TC or FTC ddI + 3TC or FTC  Expanded ≥3 drug:  Preferred: LPV/RTV (Kaletra) +  Alternative: ATV* ± RTV FPV ± RTV IDV** ± RTV SQV + RTV NFV*** EFV*** * If ATV is coadmnistered with TDF, RTV must be included in the PEP regimen. ** Avoid in late pregnancy. *** Avoid in pregnancy.

17. IF PEP: Recommended Regimen  Tenofovir/emtricitabine (Truvada®) +/ −  Lopinavir/ritonavir (Kaletra®)

18. PEP Questions  Consult Guidelines  Available at http://www.aidsinfo.nih.gov/guidelineshttp://www.aidsinfo.nih.gov/guidelines  National Clinician’s Postexposure Prophylaxis Hotline (PEPline)  Telephone consultation service: 1-888-448-4911 9 am-2 am EST

19. JR Conclusion  JR opted not to take treatment  Child tested; negative

20. Recap PEP  Determine severity of risk  Source of infection  Initiate treatment within 72 hours  Treat with Truvada +/- Kaletra  Treat for 28 days

21. Pre Exposure Prophylaxis (PrEP)

23. Pre-Exposure Prophylaxis for HIV Prevention  Antiretrovirals in HIV patients restores health and may decrease transmission of virus to uninfected partners  HIV pill taken daily or gel applied to vagina  Tenofovir (TDF) and Truvada (FTC-TDF)  Reduce risk of HIV infection  Rationale based on:  Prevention of mother to child transmission  Post exposure prophylaxis  Animal Studies

24. PREP Trials Worldwide

25. Study 1: FHI West Africa  Phase 2, randomized, double-blind, placebo-controlled  June 2004 to March 2006  Enrolled in 3 sites: Ghada, Camerron, and Nigeria  936 HIV-negative women at high risk of HIV infection  469 received TDF  467 received placebo  Safety endpoints measured by  Serum creatinine >2.0 mg/dl  Phosphorus <1.5 mg/dl  Alanine aminotranferase elevations >170 U/I  Efficacy measured by infection of HIV-1 or HIV-2

26. Study 2: Preexposure Prophylaxis Initiative (iPrEx)  Phase 3, randomized, double-blind, placebo- controlled  11 sites in six countries  July 2007-December 2009  3,324 person-years  2,499 HIV negative men or transgender women who have sex with men  1,251 given FTC-TDF  1,248 given placebo

27. Study 3: CAPRISA 004  Phase II, double-blind, randomized, placebo- controlled  May 2007-March 2010  1,341 women years  889 women at high risk of HIV through intercourse  445 tenofovir gel  444 placebo gel

28. Efficacy Results Data from FH1 West Africa TDFPlacebo Incidence Rate Person- Years of Follow-Up 232.6241.3 HIV infections/10 0 person- years 0.862.480.35 Reduction in Risk for HIV Acquisition in iPrEX Trial FTC-TDF (events) Placebo (events) Hazard Ratio HIV Infection36640.56 (0.37- 0.85) Pill Use <90% 28340.79 (0.48- 1.31) Pill Use ≥90% 8300.27 (0.12- 0.59) Effectiveness of tenofovir gel in HIV Prevention in CAPRISA 004 HIV Incidence/100 Women Years Tenofovir gel (95% CI) Placebo gel (95% CI) Incidence Rate Ratio HIV total5.69.10.61 Gel Use >80%4.29.30.46 Gel Use <50%6.28.60.72

29. Results from TDF2 and Partners PrEP  TDF2 Study –Reduced risk by 63%  Separate analysis showed 78% risk reduction  Partners PrEP  62% with Tenofovir (p=0.0003)  73% with Truvada (p<0.0001)

30. Conclusions  PrEP effective in HIV prevention  Adherence is critical  Used in high risk populations  PrEP should be used in combination with other prevention methods

31. Questions

32. References 1. CDC. HIV in the United States, July 2010. Available at http;//www.cdc.gov/hiv/resources/factsheets/us.htm. Accessed Sept 2011. 2. Hall HI, Song RG, Rhodes P, et al. Estimation of HIV incidence in the United States. JAMA 2008;300:520-9. 3. Panel on treatment of HIV-infected pregnant women prevention of perinatal transmission. Recommendations for use of antiretroviral drugs in pregnant HIV-1-infected women for use maternal health and interventions to reduce perinatal HIV transmission in the United States. September 14, 2011. pp. 1-207. Available at: http://aidsinfo.nih.gov/ContentFiles/PerinatalGL.pdf. Accessed Sept 2011.http://aidsinfo.nih.gov/ContentFiles/PerinatalGL.pdf 4. Centers for Disease Control and Prevention. Updated U.S. Public Health Service guidelines for the management of occupational exposures to HIV and recommendations for Postexposure Prophylaxis. MMWR 2005;54(No. RR-9). Available at http://aidsinfo.nih.gov/contentfiles/HealthCareOccupExpoGL.pdf. Accessed Sept 2011.http://aidsinfo.nih.gov/contentfiles/HealthCareOccupExpoGL.pdf 5. Shih CC, Kaneshima H, Rabin L, et al. Postexposure prophylaxis with zidovudine suppresses human immunodeficiency virus type 1 infection in SCID-hu mice in a time-dependent manner. J Infect Dis. 1991;163(3)625-7. 6. AVAC: Global Advocacy for HIV Prevention. PrEP trials Timeline. Available at: http://www.avac.org/ht/d/sp/i/3507/pid/3507.http://www.avac.org/ht/d/sp/i/3507/pid/3507 Accessed Sept 2011. 7. Peterson, L., Tayor, D., Roddy, R., et al. Tenofovir Disoproxil Fumarate for Prevention of HIV Infection in Women: A Phase 2, Double-Blind, Randomized, Placebo-Controlled Trial. PLOS Clinical Trials 2007:2(5):e27. 8. Grant RM, Lama JR, Anderson PL, McMahan V, Liu AY, Vargas L, et al. Preexposure Chemo-prophylaxis for HIV Prevention in Men Who Have Sex with Men. N. Engl J Med. 2010:363:27. 9. Centers for Disease Control and Prevention. Interim Guidance: Preexposure Prophylaxis for the Prevention of HIV Infection in Men Who Have Sex with Men. MMWR 2011;60(3):65-68. 10. Abdool Karim Q, Abdool Karim SS, Frohlich JA, et al. Effectiveness and safety of tenofovir gel, an antiretroviral microbicide, for the prevention of HIV infection in women. Science 2010:329:1168-74.