1. HIV PRE-EXPOSURE PROPHYLAXIS (PREP) YUMA HEALTH DISTRICT 5/23/16 ALYSSA GUIDO, MPH PROGRAM DIRECTOR, ARIZONA AETC ARIZONA AIDS EDUCATION AND TRAINING CENTER This project is supported by the Health Resources and Services Administration (HRSA) of the U.S. Department of Health and Human Services (HHS) under grant # U1OHA29292-01- 01, Regional AIDS Education and Training Centers, PAETC award: $3,018,761. This information or content and conclusions are those of the author and should not be construed as the official position or policy of, nor should any endorsements be inferred by HRSA, HHS or the U.S. Government.”

2.  Approximately 1.2 million people are living with HIV/AIDS in the United States  An estimated ~13 % of those people are undiagnosed  Since the start of the epidemic, 636,000 people have died of AIDS  An estimated 50,000 new HIV infections occur in the US every year  More than 35 million people are living with HIV/AIDS worldwide  In 2012, an estimated 2.3 million people were newly infected with HIV HIV/AIDS IN THE US AND WORLDWIDE CDC-Division of HIV/AIDS Prevention

3.  Estimated lifetime risk of an HIV diagnosis among MSM  Black/African American 1:2  Hispanic/ Latino 1:6  White 1:11  Lifetime risk of an HIV diagnosis among people with injection drug use  Male 1:36; Female 1:23  African American male 1:9; African American female 1:6  MSM 79 times the risk of heterosexuals  PWID 13 times the risk of heterosexuals CROI 2016 OA 52; Estimating the Lifetime Risk of a Diagnosis of HIV Infection in the United States Kristen Hess; Xiaohong Hu; Amy Lansky; Jonathan Mermin; H. Irene Hall; CDC, Atlanta, GA, USA Estimating Lifetime Risk of HIV Diagnosis

4.  Gay, bisexual, and other men who have sex with men (MSM) make up 64% of all HIV- infected people in the United States  The rate of new diagnoses for MSM is more than 44 times that of other men and more than 40 times that of women  African Americans are 8 times more likely to be living with HIV than whites  Hispanic /Latinos are 3 times more likely to be living with HIV than whites CONTINUED NEED FOR HIV RISK AND PREVENTION/DISPARITIES AMONG POPULATIONS

5.  Safer-sex counseling: understanding risk  Condoms and lubricant  Sterile syringes and avoiding sharing “works”  HIV testing  STI testing and treatment  PEP (post-exposure prophylaxis)  PrEP (pre-exposure prophylaxis) HIV PREVENTION

6. What is PrEP? Pre-Exposure Prophylaxis is a treatment regimen which protects the body and helps prevent HIV infection

7. What is PrEP? PrEP is not PEP PrEP is not vaccine PrEP is not a substitute for condoms

8. Pre-Exposure Prophylaxis (PrEP) HIV Infection ‘Treatment’ HIV- HIV+

9. Pre-Exposure Prophylaxis (PrEP) “Prophylaxis” – action taken to prevent disease, especially by specified means or against a specified disease. ‘ Prophylaxis’ HIV-

10. Effectiveness  PrEP Reduces risk of HIV infection by up to 92%  PrEP Does not reduce the risk of other STIs  Condoms are still the most effective method of prevention. “Will PrEP make me immune to HIV?” “Is PrEP better than condoms?” 1 Effectiveness among individuals with detectable drug levels from the iPrEx study.

11. “How often do I take PrEP?” “Can I skip doses?” “Is it like a vaccine?” How do I take PrEP?  PrEP must be taken daily  PrEP only reaches effectiveness after 20 days

13. “What will I be tested for?” Why do I need lab work before starting PrEP?  Labs will include: HIV testing (preferably 4 th generation), STI testing, Hepatitis panel, kidney function and pregnancy for women  It is possible to develop drug resistance if an HIV-infected person starts using PrEP.

14. “What are the side effects?” Is PrEP safe?  Clinical trials have shown side effects to mild, like headache and nausea  Can cause mild loss of bone mineral density (does not appear to increase risk of fractures). Bone density returns to normal levels when PrEP is stopped.  Some persons with kidney disease may not be able to take PrEP

15. I FEEL COMFORTABLE TALKING TO MY PATIENTS/CLIENTS ABOUT PREP… 1. Yes, I can talk in detail 2. A little bit, jus a few basic facts 3. No, not at all

16. I KNOW WHERE TO REFER PATIENTS TO PREP… 1. Yes, I know exactly who to refer patients to 2. I’m not sure, I’d have to do more research 3. I have no idea where to refer patients who want PrEP

17. I THINK PREP SHOULD BE… 1. Not available at all 2. Provided to patients only in select cases 3. Widely available 4. Undecided

18. I FEEL THAT PATIENTS ON PREP WILL… 1. Increase their risk behavior 2. Decrease their risk behavior 3. No change in behavior 4. I don’t know

19. I THINK PREP WILL… 1. Have a significant impact on reducing new HIV infections 2. Small impact on reducing new HIV infections 3. No impact on the epidemic 4. Unsure

20. MY TOP TWO CONCERNS ABOUT PREP ARE… 1. Not enough research on long term effects of PrEP 2. Financial concerns – who is paying for it? 3. STDs will increase due to increase in risk behavior 4. Patients will not be adherent 5. Not enough education for providers 6. Other

21. Understanding PrEP Example: Birth Control Oral Contraceptive (“The Pill”) Pre-Exposure Prophylaxis (PrEP) Prevents pregnancy if taken before sex. Does not work as morning-after pill. Prevents HIV infection pre-exposure. Will not work if already exposed. Does not always start working immediately.Does not start working immediately. Must take daily – cannot skip doses. Only helps prevent pregnancy, will not prevent STIs (should still use condoms). Only helps prevent HIV – will not prevent other STIs (should still use condoms). Very effective at preventing pregnancy, but not 100% effective. Very effective at preventing HIV infection, but not 100% effective. Should be taken by anyone who is sexually active (at risk for becoming pregnant) Should be taken by anyone who could be exposed to the HIV virus (at risk for HIV)

22. PREP AWARENESS AMONG PATIENTS IN ARIZONA N UMBER OF R ESPONDENTS T HAT H AVE H AD P ATIENTS A SK A BOUT P R EP. Provider responses to the question, “Has a patient ever asked you about PrEP?” Respondents are disaggregated by county. 51% 49%

23. PREP AWARENESS AMONG PROVIDERS IN ARIZONA N UMBER OF R ESPONDENTS T HAT I NITIATED D ISCUSSIONS A BOUT P R EP. Provider responses to the question, “Have you ever initiated a discussion about PrEP with a patient?” Provider responses disaggregated by county. 51% 49%

24. P ROVIDER E XPERIENCE WITH P R EP 33% 16% 9% 29% 13% 0 F IGURE 5. P ROVIDER E XPERIENCE WITH P R EP D ISAGGREGATED BY C OUNTY. Respondents were asked to select which statement best applies to them. The bar graph indicates the number of respondents that selected each statement. Responses are disaggregated by county.

25. iPrEx Study – MSM and transgender women in 6 countries, 44% reduction TDF2 Study - Men and Women in Botswana. 62.2 % reduction in HIV incidence Partners PrEP Study – Randomized control trial of serodiscordant couples in Kenya and Uganda, 67% reduction in HIV incidence Bangkok Tenofovir Study – IDU in Thailand, Tenofovir only, 48.9% reduction in HIV incidence Risk reduction 44% - 92% Risk reduction much higher with detectable drug levels PREP CLINICAL TRIALS

27. WHO SHOULD TAKE PREP?  June 16, 2012 FDA approved Truvada for prevention for HIV  May 14, 2014, the US Public Health Service and the CDC released the first comprehensive guidelines for PrEP.  PrEP is indicated in patients who are HIV-negative and have one of the following risk factors: 1. HIV-positive partners 2. MSM with recent unprotected sex or STD 3. Intravenous drug users (IDU) who reported sharing needles or equipment, or have recently starting substance use treatment program (high-risk for relapse). 4. Heterosexual men or women who infrequently use condoms and have sex with high- risk partners

28. NATIONAL ESTIMATE (CDC) Centers for Disease Control and Prevention (2015) Vital Signs: Estimated Percentages and Numbers of Adults with Indications for Preexposure Prophylaxis to Prevent HIV Acquisition — United States, 2015. Morbidity and Mortality Weekly Report, 64(46);1291-1295. http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6446a4.htm 1 in 41 in 51 in 200

29. Centers for Disease Control and Prevention (2015) Vital Signs: Estimated Percentages and Numbers of Adults with Indications for Preexposure Prophylaxis to Prevent HIV Acquisition — United States, 2015. Morbidity and Mortality Weekly Report, 64(46);1291-1295. http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6446a4.htm

31. 31 A CRITICAL GAP….  Restrictions in the uses of CDC and HRSA/HAB funding to pay for the medication  19 states (many in the South) have not yet adopted Medicaid expansion  Affordability of insurance remains a barrier, particularly co-payments/co-insurance for HIV medications 3-4% access it 1.2 million individuals indicated for PrEP Sources: D. Smith et al. Vital Signs Nov. 27, 2015 J. Krellenstein and J. Johnson. TAGline, Spring 2016Vital Signs TAGline

32. PREP CYCLE

33. PREP COST ESTIMATING YEARLY OUT OF POCKET COSTS lab copay (4)+ medical visit copay (4)+ medication copay (12)= Total Yearly Cost Other factors:Maximum out of PocketTruvada Patient Assistance Programs Once this is met, no more cost for services for the rest of the year Patients who qualify, might not pay anything out of pocket for medication

34. Covered by all commercial insurance companies and most Medicaid plans. Some insurance plans require Prior Authorization GILEAD’s Co-Pay Card Program Covers up to $3,600 per year, out-of-pocket costs Insured individuals only Not used with Medicaid, Medicare of VA Patient Advocate Foundation Below 400% FPL $7,500 max per year, co-pay / deductible costs – may reapply Patient Access Network Foundation – Funds currently depleted Below 500% FPL $7,500 max per year, may reapply Co-pays, deductibles, co-insurance Accessing PrEP – Insured Individuals

35. Gilead Medication Assistance Program Below 500% FPL Re-apply as needed Only covers medication costs – does not medical appointments and lab costs Community health centers have a sliding scale fee and can provide medical care and labs Accessing PrEP – Uninsured Individuals

36. CONCLUSIONS  PrEP is recommended as one prevention option for sexually active MSM, heterosexual men and women, IDU at substantial risk of HIV acquisition  Adherence is a key factor in PrEP efficacy  Before prescribing PrEP, HIV infection must be excluded, and the patient should be assessed for comorbidities that may present health risks  The recommended PrEP regimen is fixed-dose TDF/FTC (Truvada)  Patients prescribed PrEP need to return for follow-up visits at least every 3 months and be retested for HIV  Affordability of PrEP can pose a barrier but there are patient assistance programs that can help with co-pays.

37.  Does patient have PCP willing to prescribe PrEP?  Is the patient willing to switch PCPs if necessary? CONNECT TO A PREP PROVIDER

38. POST EXPOSURE PROPHYLAXIS (PEP)

39. Alyssa Guido, MPH Program Director Arizona AIDS Education & Training Center 520-626-0723 alyssa1@deptofmed.arizona.edu THANK YOU Physician Resource Line for Clinical Consultations Local: (520) 694-5868 Long Distance: (800) 328-5868 Mexico: 001-800-328-5868 * Ask for the Infectious Disease Specialist on call

40. EXTRA SLIDES

41. MICHAEL  You are evaluating a 23 year-old male at your office.  He has no active complaints. He is sexually active with men and had six partners over the past year.  He has a history of syphilis diagnosed two-years ago and was treated with IM penicillin.  Six months ago, you counseled him on the importance of consistent condom use.  He reports that he currently uses condoms ~80% of the time.  No recent STD since last visit. He drinks alcohol occasionally and no illicit drug use.

42. WHAT WOULD YOU RECOMMEND FOR MICHAEL? 1. HIV screening 2. HIV and STD screening 3. HIV, STD screening and discuss importance of persistent condom use 4. Offer daily Truvada (TDF/FTC) + HIV, STD screening and discuss importance of persistent condom use

43.  Randomized clinical trial- 4905 subjects  Truvada (TDF/FTC) was shown to decrease the risk of HIV transmission by 42% in MSM who also received comprehensive preventive services  The risk was decreased by 92% in patients with detectable drug levels PRE-EXPOSURE CHEMOPROPHYLAXIS FOR HIV PREVENTION IN MEN WHO HAVE SEX WITH MEN - THE IPREX TRIAL Grant RM, et al. N Engl J Med 2010;363:2587-99

44. GRANT RM ET AL. N ENGL J MED 2010;363:2587-2599. P RE - EXPOSURE CHEMOPROPHYLAXIS FOR HIV PREVENTION IN MEN WHO HAVE SEX WITH MEN - THE IPREX TRIAL

45.  Truvada (TDF/FTC) was shown to decrease the risk of HIV transmission by 75% in uninfected individuals in stable heterosexual serodiscordant relationship who also received comprehensive preventive services  Tenofovir alone decreased the risk by 67%.  The risk was decreased by 90% in patients with detectable TDF and FTC levels  8 patients were infected with HIV before randomization. Resistant HIV to the study medications developed in 2 cases  No participants who acquired HIV after randomization developed resistance ANTIRETROVIRAL PROPHYLAXIS FOR HIV PREVENTION IN HETEROSEXUAL MEN AND WOMEN- THE PARTNERS-PREP TRIAL B AETEN JM ET AL. N E NGL J M ED 2012;367:399-410.

46. PrEP Clinical Trials Iniciativa Profilaxis Pre-Exposición (iPrEx) Study 1 Randomized clinical trial of gay and bisexual men 2499 Participants in 6 countries PrEP group overall 44% less likely to get HIV than those who were given a placebo. Risk of infection reduced by 92% in men with detectable levels of drug in bloodstream. 1 Grant RM et al. Preexposure Chemoprophylaxis for HIV Prevention in Men Who Have Sex with Men N Engl J Med 2010;363:2587- 2599

47. TDF2 Study Among Men and Women in Botswana 2 Heterosexually active men and women in Botswana Randomized clinical trial of 1219 participants PrEP reduced the risk of getting HIV by 62% Participants who became infected had less drug in their blood compared to those who remained uninfected. 2 Thigpen, MC et al. Antiretroviral Preexposure Prophylaxis for Heterosexual HIV Transmission in Botswana N Engl J Med 2012; 367:423-434 Pr EP Clinical Trials

48. The Partners PrEP Study 3 HIV discordant couples in Kenya and Uganda Randomized clinical trial of 4,747 participants PrEP group 75% less likely to become infected than those on placebo. Among those with detectable levels of medicine in their blood, PrEP reduced the risk of HIV infection by 90%. Pr EP Clinical Trials 3 Baeten JM, Donnell D, Ndase P, et al. Antiretroviral Prophylaxis for HIV-1 Prevention among Heterosexual Men and Women. The New England journal of medicine 2012;367(5):399-410. doi:10.1056/NEJMoa1108524.

49. 4 Choopanya, Kachit et al. Antiretroviral prophylaxis for HIV infection in injecting drug users in Bangkok, Thailand (the Bangkok Tenofovir Study): a randomised, double-blind, placebo-controlled phase 3 trial, The Lancet, Volume 381, Issue 9883, 15–21 Bangkok Tenofovir Study 4 Placebo-controlled clinical trial (tenofovir vs placebo) 2413 Injection drug users in Thailand Tenofovir group had reduced risk of HIV by 49% Participants with detectable tenofovir in their blood, risk of infection reduced by 74% Pr EP Clinical Trials