HIV Pre-Exposure and Post-Exposure Prophylaxis

1. HIV Pre-Exposure and Post-Exposure Prophylaxis Margaret Caplan, MD UCLA, Division of Infectious Diseases August 26, 2013

2. Case #1 • Ms. A is a 29 year-old HIV(+) African-American female, diagnosed in January 2012and is ARV-naïve. Her lowest CD4 count is 766/28% with a viral load of 2261 copies/mL (peak VL 10K at time of infection). She and her partner currently use condoms regularly. • Her boyfriend is HIV(-). He heard about Truvadaand wants to know if he should start taking an anti-retroviral pill to reduce his risk of acquiring HIV. • Would you recommend that he take Truvada?

3. Case #2 • Mr. C is a 26 year-old male with a history of multiple bouts of syphilis and gonorrhea. He reports using condoms most of the time, although sometime he ‘forgets’ or ‘it just doesn’t feel right.’ He has had more that 50 male sexual partners in the last year. He knows that he is at risk of HIV infection and gets tested every 6 months. Last screening test was negative one month ago. • He asks about taking Truvadaand says that he might have taken it once or twice before from a friend. • Would you recommend he take Truvada?

4. Case #3 • Mr. T is a 62 year-old Caucasian male diagnosed with HIV in 1994. He has been stable with a CD4 count 600-800s and HIV VL <50 since 2003. He is married to an HIV(-) man to whom he has been committed for the past 15 years. They do not use condoms regularly. His husband gets tested for HIV routinely and “has always been negative.” • Mr. T also has heard about Truvada in the news. He asks you if there is any added protective benefit of Truvada for his husband. • Would you recommend Mr. T’s husband take Truvada?

5. Case #4 • Mr. G is a 30 year-old HIV (+) African-American male for a routine office visit. He is doing very well on Atripla, with a CD4 count 359/15% and HIV viral load <40copies/mL. He recently got married to an HIV (-) woman. They have been talking about starting a family and currently use condoms regularly. He is on disability, and their income is limited. • He and his wife have heard about Truvada in the news. He asks if you would recommend that his wife take Truvada while they are trying to conceive a child. • Would you recommend that his partner take Truvada?

6. Number & percentage of HIV-infected persons engaged in selected stages of the continuum of HIV care – United States

8. CDC.Gov 2011

10. Susceptible Person (target cells) HIV-infected Person (virions) Sista ND et al. ClinInvestig2011

11. Susceptible Person (target cells) HIV-infected Person (virions) Sista ND et al. ClinInvestig2011

12. MODES OF TRANSMISSION Sexual Blood borne/parenteral Mother-to-child Susceptible Person (target cells) HIV-infected Person (virions) Sista ND et al. ClinInvestig2011

13. MODES OF TRANSMISSION Sexual Blood borne/parenteral Mother-to-child Susceptible Person (target cells) HIV-infected Person (virions) Activated immune system Increased viral load Improved efficiency of transmission Sista ND et al. ClinInvestig2011

14. MODES OF TRANSMISSION Sexual Blood borne/parenteral Mother-to-child Susceptible Person (target cells) HIV-infected Person (virions) Activated immune system Increased viral load Improved efficiency of transmission Sista ND et al. ClinInvestig2011

15. MODES OF TRANSMISSION Sexual Blood borne/parenteral Mother-to-child Interventions: -Reduce high-risk behavior -Treat HIV -Treat other STIs Susceptible Person (target cells) HIV-infected Person (virions) Activated immune system Increased viral load Improved efficiency of transmission Sista ND et al. ClinInvestig2011

16. MODES OF TRANSMISSION Sexual Blood borne/parenteral Mother-to-child Interventions: -Reduce high-risk behavior -Treat HIV -Treat other STIs Interventions: -Reduce high-risk behavior -Block with barriers -Reduce susceptibility (e.g. male circumcision, treat STIs) -Blood and needle safety -PrEP Susceptible Person (target cells) HIV-infected Person (virions) Activated immune system Increased viral load Improved efficiency of transmission Sista ND et al. ClinInvestig2011

17. “Combined Prevention”

18. “Combined Prevention”

19. Defining our terms… Prophylaxis: medication used to prevent a disease Pre-exposure prophylaxis: medication taken before an exposure to a disease to prevent acquisition of the disease Post-exposure prophylaxis: medication taken after an exposure a disease to prevent acquisition of the disease

20. Current Language of Prevention • HIV-infected • Treatment as Prevention (TasP) • HIV-uninfected • Pre-exposure prophylaxis (PrEP) • Topical tenofovir gel • Oral tenofovir/emtricitabine • Post-exposure prophylaxis (PEP)

21. Current Language of Prevention • HIV-uninfected • Pre-exposure prophylaxis (PrEP) • Topical tenofovir gel • Oral tenofovir/emtricitabine, tenofovir • Post-exposure prophylaxis (PEP)

22. AVAC.org 2012

23. AVAC.org 2012

24. Current Language of Prevention • HIV-uninfected • Pre-exposure prophylaxis (PrEP) • Topical tenofovir gel • Oral tenofovir/emtricitabine, tenofovir • Post-exposure prophylaxis (PEP)

25. Current Language of Prevention • HIV-uninfected • Pre-exposure prophylaxis (PrEP) • Topical tenofovir gel • Oral tenofovir/emtricitabine, tenofovir • Post-exposure prophylaxis (PEP)

26. Topical Tenofovir: A First Success • CAPRISA 004 Trial, South Africa • 889 women randomized to tenofovir gel and placebo gel groups. • Tenofovirgel reduced HIV acquisition by an estimated 39% (P=0.0017) overall, and by 54% (P=0.025) in women with high gel adherence (>80%). Karim et al. Science 2010

27. Karim et al. Science 2010

28. Other Microbicide Trials • CAPRISA 008: Phase III, continuation of 004 • HPTN • Multiple studies • Vaginal and rectal gel formulations • MTN: • Dalpivirine ring (ASPIRE and The Ring Study) • Vaginal ring used monthly, study in African women.

29. AVAC.org 2011

30. Current Language of Prevention • HIV-uninfected • Pre-exposure prophylaxis (PrEP) • Topical tenofovir gel • Oral tenofovir/emtricitabine • Post-exposure prophylaxis (PEP)

31. “Daily Pill Greatly Lowers AIDS Risk, Study Finds”November 23, 2010

32. Oral PrEP Grant et al N Engl J Med 2010 Thigpen et al N Engl J Med 2012 Baeten et al N Engl J Med 2012

33. **All as part of a comprehensive prevention package** • HIV testing • Risk-reduction counseling and condoms • Diagnosis and treatment of symptomatic STIs (GC.C, syphilis, and HSV-2), as well as screening in asymptomatic individuals and partners • +/- Referral for PEP if reporting a recent exposure to HIV • +/- Hepatitis B vaccination

34. VOICE http://www.mtnstopshiv.org/node/2003

35. http://www.mtnstopshiv.org/node/2003

36. Why didn’t PrEP ‘work’? • Pharmacokinetics: Absorption? Metabolism? Interactions? • Risk perception: Approximately 70% women did not believe that they were at risk of HIV-infection at baseline and during the FEM-PrEP study. • ADHERENCE?! • Upwards of 90% based on self-reporting • BUT less than ~30% based on measurable drug levels Van Damme et al. N Engl J Med2012 http://www.mtnstopshiv.org/node/2003

37. What next?

38. AVAC.org 2011

39. Issues with PrEP • Availability of other “less toxic” or sustainable alternatives (i.e. condoms, circumcision) • Fear of “risk compensation” • Cost and allocation of resources • Drug resistance • Hepatitis B infection • Prescriber training, monitoring

40. CDC Guidelines: Truvadaas PrEP http://www.cdc.gov/hiv/prevention/research/prep/ • For use in high-risk MSM, January 28, 2011 *FDA approval July 16, 2012 for HIGH-RISK HIV- UNIFECTED individuals* • For use in high-risk heterosexual men and women, August 9, 2012 • For use in injecting drug users, June 14, 2013

41. CDC Interim Guidelines CDC.gov 2012

42. CDC on discontinuing PrEP • Perform HIV test to confirm whether infection has occurred. • If HIV positive, order and document results of resistance testing, establish linkage to care. • If HIV negative, establish linkage to care for risk reduction support services as indicated. • If active hepatitis B is diagnosed at initiation of PrEP, consider appropriate medication for continued treatment of hepatitis B infection. • If pregnant, inform pre-natal care provider of TDF/FTC use in early pregnancy and coordinate care to maintain HIV prevention during pregnancy and breastfeeding. CDC.gov 2012

43. Current Language of Prevention • HIV-infected • Treatment as Prevention (TasP) • HIV-uninfected • Pre-exposure prophylaxis (PrEP) • Topical tenofovir gel • Oral tenofovir/emtricitabine • Post-exposure prophylaxis (PEP)

44. Post-Exposure Prophylaxis (PEP) • Efficacy based on animal studies, perinatal clinical trials, studies of health-careworkers, and observational data • Risk based on degree of exposure

45. www.cdc.gov

46. Post-Exposure Prophylaxis (PEP) CDC Guidelines for use in: • Occupational exposures • Non-occupational exposures (nPEP) • Persons wounded during bombings and other mass casualty events • Sexual, injection-drug-use, or other non- occupational exsposures www.cdc.gov

48. Non-occupational HIV Exposure Algorithm www.cdc.gov

49. Post-Exposure Prophylaxis (PEP) • Ideally, started as soon as possible within 72 hours after exposure to be most effective. • Multi-drug (3+) regimen recommended for 4 weeks. • Follow-up testing out to six months is important to ensure clearance.

50. Current Language of Prevention HIV-uninfected, high-risk population • Pre-exposure prophylaxis (PrEP) • Topical tenofovir gel • Oral tenofovir/emtricitabine, tenofovir • Post-exposure prophylaxis (PEP)