Pre-Exposure Prophylaxis ANTONIO E. URBINA, MD Medical Director Mt. Sinai Institute for Advanced Medicine

Transcription

1 Pre-Exposure Prophylaxis ANTONIO E. URBINA, MD Medical Director Mt. Sinai Institute for Advanced Medicine

2 REVIEW OF PREP GUIDELINES: A PRIMER FOR THE PRIMARY CARE PRACTITIONER PrEP Webinar Series

3 Disclosure Advisory Board: Merck, Theratechnologies Research Support: Gilead

4 LEARNING OBJECTIVES: 1. Discuss the NYS and CDC Guidelines for Pre- Exposure Prophylaxis (PrEP) 2. Describe selection of candidates for PrEP 3. Discuss the management of the patient on PrEP 4. Discuss PrEP therapy and side effects 5. Discuss the challenges associated with PrEP 6. Discuss follow-up care including labs, PrEP, and counseling

5 FDA Approval In July 16, 2012, FDA approved the use of tenofovir (300mg) + emtricitabine (200 mg) (TDF/FTC or Truvada ) for HIV PrEP in adults who are at high risk for becoming HIV-infected Dosage: One tablet once daily taken orally with or without food Four trials found PrEP to be effective for preventing HIV infection when taken as prescribed 1,2,3,6 FEM-PrEP and VOICE trials in females did not show a benefit, likely because of poor adherence 4,5 All trials found PrEP to be safe 1. Grant RM, et al. Preexposure chemoprophylaxis for HIV prevention in men who have sex with men. N Engl J Med2010;363: Baeten JM, et al. Antiretroviral prophylaxis for HIV prevention in heterosexual men and women. N Engl J Med 2012;367: Thigpen MC, et al. Antiretroviral preexposure prophylaxis for heterosexual HIV transmission in Botswana. N Engl J Med 2012;367: Van Damme L,et al. Preexposure prophylaxis for HIV infection among African women. N Engl J Med 2012;367: Marrazzo J et al. Pre-exposure prophylaxis for HIV in women: Daily oral tenofovir, oral tenofovir/emtricitabine or vaginal tenofovir gel in the VOICE study (MTN 003). 20th Conference on Retroviruses and Opportunistic Infections, Atlanta, abstract 26LB, Choopanya K, Martin M, Suntharasamai P, et al. Antiretroviral prophylaxis for HIV infection in injecting drug users in Bangkok, Thailand (the Bangkok Tenofovir Study): A randomized, double-blind, placebo-controlled phase 3 trial. Lancet 2013;381:

6 iprex Trial

7 iprex Trial Phase 3, double-blind, randomized, placebo-controlled, 11 sites in 6 countries Adult HIV-MSM or transgender women in the US, Peru, Ecuador, Brazil, Thailand, South Africa Two study arms: TDF/FTC (300mg/200mg) orally once daily Placebo Primary Outcome: Prevention of HIV Grant RM, Lama JR, Anderson PL, et al. Preexposure chemoprophylaxis for HIV prevention in men who have sex with men. N Engl J Med2010;363:2587-2

8 iprex Study Subjects Inclusion Criteria Male sex at birth Age 18+ HIV-seronegative High risk for HIV acquisition Lab inclusion criteria: CBC, BMP, LFTs Exclusion Criteria Serious and active illness: Diabetes, TB, Cancer Active substance abuse Nephrotoxic agents Pathological bone fractures Grant RM, Lama JR, Anderson PL, et al. Preexposure chemoprophylaxis for HIV prevention in men who have sex with men. N Engl J Med2010;363:2587-2

9 iprex Study Procedures Study visits every 4 weeks after enrollment Comprehensive package of prevention services: Risk reduction counseling, condoms, diagnosis and treatment of STI s Rapid testing for HIV antibodies Grant RM, Lama JR, Anderson PL, et al. Preexposure chemoprophylaxis for HIV prevention in men who have sex with men. N Engl J Med2010;363:2587-2

10 iprex Results 44% reduction, P= % CI (15-63%) Grant RM, Lama JR, Anderson PL, et al. Preexposure chemoprophylaxis for HIV prevention in men who have sex with men. N Engl J Med2010;363:2587-2

11 iprex Results TDF/FTC was well tolerated Nausea (2% versus <1%) and weight loss >5% (2% versus 1%) were more common among those taking medication than those on placebo No differences in severe (grade 3) or life-threatening (grade 4) laboratory abnormalities were observed between groups No drug resistant virus was found in the 100 participants infected after enrollment Grant RM, Lama JR, Anderson PL, et al. Preexposure chemoprophylaxis for HIV prevention in men who have sex with men. N Engl J Med2010;363:2587-2

12 Risk Compensation Grant RM, Lama JR, Anderson PL, et al. Preexposure chemoprophylaxis for HIV prevention in men who have sex with men. N Engl J Med2010;363:2587-2

13 iprex: HIV by Group and Drug Detection Group Drug Detection HIV Infections Incidence Density Placebo No FTC/TDF No Yes Relative Rate Reduction by use of FTC/TDF 92% Grant RM, Lama JR, Anderson PL, et al. Preexposure chemoprophylaxis for HIV prevention in men who have sex with men. N Engl J Med2010;363:2587-2

14 Prep Efficacy Trials Study Name Population N Results Efficacy By Detection of Drug Partners PrEP TDF2 Study iprex Heterosexual couples Heterosexual Men and Women MSM/trans women 4,758 TDF: 67% efficacy FTC/TDF: 75% efficacy Kahle E, et al. 19th IAC; Washington, DC; July 22-27, 2012; Abst. TUAC % 90% 1,219 FTC/TDF: 62% efficacy 85% 2,499 FTC/TDF: 44% efficacy 92% FEM-PrEP Women 1,951 FTC/TDF: futility NR VOICE Women 5,029 TDF, TDF/FTC, Vaginal TFV gel: futility Thai IVDU IVDU 2,413 TDF: 49% efficacy 74% NR

15 US Public Health Service PrEP Guidelines Background On May 14 th, 2014, CDC released clinical, practice guidelines for PrEP: Provide clear criteria for determining a person s HIV risk and indications for PrEP use Require that patients receive HIV testing to confirm negative status before starting PrEP Underscore importance of counseling about adherence and HIV risk reduction, including encouraging condom use for additional protection

16 US Public Health Service PrEP Guidelines Background Recommend regular monitoring of HIV infection status, side effects, adherence, and sexual or injection risk behaviors Include a providers supplement with additional materials and tools for use when prescribing PrEP Recommend that PrEP be considered for people who are HIV negative and at substantial risk for HIV

17 CDC Defines Substantial Risk For sexual transmission, this includes anyone who is in an ongoing relationship with an HIV-positive partner. It also includes anyone who (1) is not in a mutually, monogamous relationship with a partner who recently tested HIV-negative, and (2) is a: Gay or bisexual man who has had anal sex without a condom or been diagnosed with an STD in the past 6 months or Heterosexual man or woman who does not regularly use condoms during sex with partners of unknown HIV status who are at substantial risk of HIV infection For example, people who inject drugs or have bisexual male partners

18 CDC Defines Substantial Risk For people who inject drugs, this includes those who have injected illicit drugs in the past 6 months and who have shared injection equipment or been in drug treatment for injection drug use in the past 6 months. Providers should also discuss PrEP with HIV discordant couples during conception and pregnancy As one of several options to protect the HIV-negative partner PrEP is only for people who are at ongoing, substantial risk of HIV infection. Post exposure prophylaxis (PEP) should be offered to people who present after a single high-risk event of potential HIV exposure

19 NYS DOH Guidance for the Use of PrEP On Jan 14 th, 2014 NYS DOH published Guidance for the Use of PreP to Prevent HIV transmission

20 NYS DOH Guidance Candidates for PrEP: PrEP is indicated for individuals who have a documented negative HIV test and are at ongoing, high risk for HIV infection Negative, HIV test result needs to be confirmed as close to initiation of PrEP as possible PrEP is not meant to be used as a lifelong intervention, but rather as a method of increasing prevention during high risk periods

21 NYS DOH Guidance Candidates for PrEP Providers need to obtain a thorough sexual and drug use history and regularly discuss risk-taking behaviors For example, How many episodes of condomless intercourse or unsafe injecting practices have occurred? Encourage safer-sex practices and safer injection techniques Individuals who do not have continued risk, should be educated about non-occupational post exposure prophylaxis

22 MSM who engage in unprotected anal intercourse 1,2 NYS DOH Guidance Candidates for PrEP Stimulant drug use, especially methamphetamine 4 Individuals in a sero-discordant sexual relationship, especially during attempts to conceive Individuals with 1 ano-genital STI per year 5 Transgender individuals Individuals who have been prescribed npep with continued high-risk behavior or multiple courses 6 IDUs, including injecting hormones 3 Individuals engaging in transactional sex 1. Smith DK, et al. Development of a clinical screening index predictive of incident HIV infection among men who have sex with men in the United States. J Acquir Immune Defic Syndr 2012;60: Grov C, et al. HIV risk in group sexual encounters: An event-level analysis from a national online survey of MSM in the U.S. J Sex Med 2013;10: Choopanya K, et al. Antiretroviral prophylaxis for HIV infection in injecting drug users in Bangkok, Thailand. 4. Zule WA, et al. Methamphetamine use and risky sexual behaviors during heterosexual encounters. Sex Transm Dis2007;34: Menza TW, et al. Prediction of HIV acquisition among men who have sex with men. Sex Transm Dis 2009;36: Heuker J, et al. High HIV incidence among MSM prescribed postexposure prophylaxis, : Indications for ongoing sexual risk behaviour. AIDS 2012;26:

23 Smith DK, Pals SL, Herbst JH, et al. Development of a clinical screening index predictive of incident HIV infection among men who have sex with men in the United States. J Acquir Immune Defic Syndr2012;60:

24 NYS DOH Guidance Contraindications to PrEP Psycho-Social Lack of readiness and/or ability to adhere Efficacy of PrEP is dependent on adherence to ensure that plasma drug levels reach a protective level Medical Documented HIV Infection Drug resistant HIV has been identified in patients with undetected HIV who subsequently received TDF/FTC for PrEP Kidney Dysfunction CrCl <60 ml/min

25 NYS DOH Guidance Contraindications to PrEP Although consistent condom use is a critical part of a prevention plan for all persons prescribed PrEP Lack of use of barrier protection is not a contraindication to PrEP

26 NYS DOH Guidance Important Considerations for PrEP Does the patient have chronic active hepatitis B? Is the patient pregnant or attempting to conceive? Is the patient an adolescent? Is the patient taking other nephrotoxic drug or drugs that interact with TDF/FTC? Although not FDA- approved for treatment of HBV, TDF/FTC may be used to treat hepatitis B Discontinuation may cause flare Discuss the known risks and benefits Providers need to report to the Antiretroviral Pregnancy Registry No data in 18 years of age Obtain a thorough medication history. Especially chronic use of NSAIDs Does patient have osteopenia/osteomalacia/osteoporosis? Discuss risk of bone loss, especially those with risk factors

27 NYS DOH Guidance Pre-Prescription: Assessment Checklist Symptoms of Acute HIV Infection Febrile, flu, or mono -like illness in last 6 weeks Medication List Substance Use and Mental Health Screening Knowledge about PrEP Patient understanding and misconceptions Health Literacy Readiness and Willingness to adhere to PrEP Primary Care Does the patient have a PCP? Partner Information Determine status of partners Domestic Violence Screening Housing Status Means to Pay for PrEP Is patient insured? Reproductive Plans (for Women)

28 NYS DOH Guidance Pre-prescription education The pill Truvada has two drugs in it that are commonly used to treat HIV in persons who are HIV-positive. When taken daily by people who are HIV-negative, they can block HIV from infecting the body. The pill needs to be taken every day in order for the body to build up sufficient drug levels to block HIV. It cannot be expected to work if it is only taken just before or just after sex. PrEP reduces but does not eliminate HIV transmission risk. You still need to use condoms if you are taking PrEP because PrEP does not protect against other sexually transmitted diseases.

29 Educate about the following: NYS DOH Guidance Pre-Prescription: Patient Education Talking Points: How PrEP works Limitations of PrEP PrEP Use Common side effects Explain how PrEP works in language that is easy to understand Explain how PrEP works as part of a comprehensive, prevention plan Efficacy dependent on adherence Reduces but does not eliminate HIV risk Does not protect against other STIs Dosing and need for daily adherence # of sequential doses to achieve protective effect 1,2,3 Reinforcement of condom use in period following missed doses H/A, abdominal pain, weight loss. Side effects resolve/improve after first month Standard measures (anti-diarrheal, antigas, anti-emetics) should be used to alleviate sxs 1. Anderson PL, et al. Emtricitabine-tenofovir concentrations and pre-exposure prophylaxis efficacy in men who have sex with men.sci Transl Med 2012;4:151ra Hendrix CW, et al. MTN-001: Randomized pharmacokinetic cross-over study comparing tenofovir vaginal gel and oral tablets in vaginal tissue and other compartments. PLoS One 2013;8:e Patterson KB, et al. Penetration of tenofovir and emtricitabine in mucosal tissues: Implications for prevention of HIV-1 transmission. Sci Transl Med 2011;3:112re4.

30 NYS DOH Guidance Pre-Prescription: Patient Education Educate about the following: Long-term safety of PrEP Baseline tests and schedule for monitoring Criteria for discontinuing Talking Points: 24-month f/u data suggest clinical safety of oral TDF in HIV negative persons 1 Explain that tests have to be taken before prescribing Explain importance of f/u monitoring, including HIV testing at least every 3 months Positive HIV test result: PrEP needs to be stopped immediately Development of renal disease Non-adherence to medication or appointments Change in risk-behavior (i.e. PrEP is no longer needed) Use of medication for unintended purposes 1. Grohskopf LA, et al. Randomized trial of clinical safety of daily oral tenofovir disoproxil fumarate among HIV-uninfected men who have sex with men in the United States. J Acquir Immune Defic Syndr 2013;64:79-86.

31 1. Birkhead GS, et al. Acquiring human immunodeficiency virus during pregnancy and mother-tochild transmission in New York: Obstet Gynecol 2010;115: NYS DOH Guidance Pre-Prescription: Patient Education Educate about the following: Symptoms of Acute Sero-conversion For Women: Potential Benefits/Risks if Pregnancy Occurs During Use of PreP Benefits Potential Toxicity Talking Points: Alert patients to contact PCP if: fever, rash, joint pain, oral ulcers, fatigue, night sweats, sore throat, malaise, pain in muscles, loss of appetite Decrease risk of acute HIV Infection, which is significant risk factor for MTCT 1 Data suggest that TDF/FTC does not increase risk of birth defects; however, not enough data to exclude the possibility of harm 2

32 NYS DOH Guidance Pre-prescription: Lab Tests HIV Test Obtain 3 rd or 4 th generation HIV test Perform viral load test for HIV for: Patient with sxs of AHI or whose HIV AB is negative but reports unprotected sex in last month Basic Metabolic Panel Do not start PrEP if CrCl <60 ml/min Urinalysis Identify pre-existing proteinuria Serology for Hep A, B and C (Immunize for A and B if not immune) Screen for sexually transmitted infections, GC and chlamydia (genital, rectal, pharyngeal) RPR for syphilis Consider vaccinations for HPV and meningococcus, if indicated Pregnancy Test

33 NYS DOH Guidance Prescribing PrEP The first prescription of TDF/FTC should only be for 30 days At the 30 day visit (after assessing adherence, tolerance and commitment), a prescription for 60 days may be given Creatinine and CrCl for patients with borderline renal function or at increased risk for kidney disease (>65 years of age, black race, HTN or DM) After 3 month visit, prescriptions can be given for 90 days provided that patient is adherent Patient should then return for 3-month visits for HIV testing and other assessments:

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35 NYSDOH Guidance Discontinuation of PrEP Immediately, if patient receives a positive HIV test result Big risk of resistance if patient is maintained on TDF/FTC only Obtain a genotypic assay and refer and link to HIV care Discontinuation of TDF/FTC in patients with chronic active hepatitis B can cause exacerbations of hepatitis B Develops renal disease Non-adherent to medication or appointments after attempts to improve Using medication for purposes other than intended Reduce risk behaviors to the extent that PrEP is no longer needed

36 Summary PrEP is now part of a menu of evidence-based interventions to prevent HIV transmission. Although the overall number of new HIV infections is decreasing in NYS, subpopulations such as young MSM continue to increase--especially in young, black men. PrEP may be an effective option to augment behavior change in these high-risk populations.

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38 Questions? Antonio E. Urbina, MD Clinical questions regarding PrEP? Please phone the CEI Line at or visit

39 ACCESSING PREP: STRATEGIES AND BARRIERS TO CARE Rachel Legatt, LMSW Social Worker Mt. Sinai Institute for Advanced Medicine

40 There are no disclosures DISCLOSURE

41 LEARNING OBJECTIVES: 1. Identify strategies to introduce and promote a PrEP program in a clinical setting 2. Describe methods to connect interested patients with PrEP utilizing an interdisciplinary team 3. Recognize logistical processes and limitations in providing PrEP services

42 Locating PrEP candidates Existing patients Routine Exams HIV testing and counseling; STI testing and results PEP (Post Exposure Prophylaxis) Concern or change in partner status/change in risk Curiosity/interest in PrEP Role of interdisciplinary team in recruitment Advertising availability PrEP services for new patients Agency website In-office brochures Community referrals Social media and relevant apps: Facebook, Twitter, Grindr

43 Connecting with new patients Agency overall must recognize PrEP patient R/O PEP, HIV positive, other unrelated Ensure agency education around PEP vs. PrEP Example: Mt. Sinai Institute for Advanced Medicine Spencer Cox Clinic PEP vs. PrEP reference For reception and call center staff

44 PrEP vs. PEP reference PrEP Pre-Exposure Prophylaxis This is a visit where a future appointment would need to be made as if it were an initial medical appointment. The patient has not had one particular incident occur recently, but would like to possibly be using medication for longer term protection. PEP Post-Exposure Prophylaxis This is a visit that would be made when the patient has had a VERY recent exposure to HIV, at least within the past 72 Hours. The patient could potentially be very nervous and have been referred from an Emergency room and told to follow up at our site. They might have also been given a few days of medications A patient could see the social worker as a walk-in to hear more, establish insurance, and get an HIV test, but ultimately will be scheduled out as a normal NPO appointment (with additional time if need a rapid HIV test) before seeing a provider. A walk-in visit will be conducted. The patient will meet with a social worker who will give them some options to ensure treatment is continued. The patient needs to be placed on a medical provider s schedule- the visit is considered an emergency. Questions to clarify: Did you receive a referral regarding PrEP? Did something happen in the last 3 days that you are concerned about? o If no, follow PrEP protocol. o If yes, patient actually might be seeking PEP, and should follow a PEP walk-in emergency visit. Questions to clarify: Did something happen in the last 3 days that you re concerned about? o If yes, patient is most likely seeking PEP and should be scheduled as a walk-in. o If no, clarify that patient might be seeking PrEP. From there, follow PrEP protocol

45 Interdisciplinary PrEP services Where available Social worker / Case manager / HIV counselor / educator Inter-agency collaboration as alternative Additional time to spend with patients Weigh pros and cons PrEP, discuss fears Inform about on use, insurance, guide through process Often have counseling training and experience Sexual health counseling, PrEP decision counseling

46 Raising the PrEP question Open-ended, patient-centered, non-judgmental Have you heard about PrEP, or pre-exposure prophylaxis? If so, what do you think about PrEP? If not, could I provide you a brief explanation? Create a safe space for consideration Look out for myths or misconceptions: My friend said I heard that I had a friend that Misconceptions often tied to fear of stigmatization or side effects Misconceptions often a PrEP deterrent

47 Differentiating PrEP vs. PEP Often confusion between the two Provide a general definition of each in patient POV PEP (Post): I think I may have been exposed to HIV, so I will take 1 month of medications to try to prevent becoming infected PrEP (Pre): I haven t had a recent exposure, but I m worried I might be at risk, so I will take a medication daily to try to prevent infection

48 Describing PrEP 1 pill once a day - Truvada Adherence is essential Discuss relationship efficacy and adherence Monitoring in PrEP, discuss frequency Benefits of having PCP Ensuring negative status Evaluating timeline for being on PrEP

49 PrEP stigmatization Fear of side effects Short and long-term, specifically bone loss Fear/dislike of taking medications Opportunity for a cost-benefit analysis Fear of peer judgment Labeling individual s behaviors Being grouped with a specific population/action Pervasive in practice

50 Addressing PrEP stigma Discuss the literature What PrEP can do and benefits, research study results Discuss personal choice Does this work for your health and your life? Discussing NOT going on PrEP What would it mean for you to test positive for HIV? Address self-stigmatizing beliefs Do you feel you would pursue risky behaviors if you went on PrEP? If so, would this be a concern for you?

51 Analogy of prevention toolbox Contains what you choose to add More effective with additions Fewer tools better than an empty toolbox Toolbox can contain any combination: Condom use PrEP for individual Partner undetectable on ARVs or on PrEP Patient decision, not provider/friend/partner

52 Condoms Condoms remain part of prevention dialogue Safe space allows for openness and honesty Importance of recognizing pre-conceived notions or discomfort Remembering cost/benefit analysis and toolbox: On PrEP & no condoms > no condoms & no PrEP Recall end goal of preventing HIV

53 HIV education Should be integrated into PrEP process Gain familiarity of how HIV is transmitted Enhancing understanding of safer sex with positive partners/partners of unknown status Improving understanding of risk Reduction HIV stigma

54 Bringing partner into conversation Relationship status: if in a relationship: Open or closed? For individual/partner? Partner testing? Positive partner? On ARVs? Discuss and educate about labs, undetectable status Negative partners- is PrEP being considered? Patient & partner s beliefs/fears raised and discussed Potential for changed dynamics in relationship Fear reduction possible in serodiscordant couples and/or couples in open relationships

55 Age of Grindr Increased availability/openness Increased potential for education Increased potential for prevention messaging Work within modern context Non-judgmental and patientcentered Utilize as opportunity for dialogue

56 PrEP pros and cons Ask what patient sees as the benefits and risks of PrEP: Do you feel this could be a relevant tool for you? Why or why not? Pros: lowered risk HIV, health promoting for patient and partners, maintaining HIV negative status, an effective strategy removed from encounter (unlike condoms) Cons: medication side effects, needing to take medication daily, stigma (concept of promiscuity)

57 Connecting patient to PrEP If patient interested in PrEP, ensure connection to services Can patient schedule an appointment at the clinic? Assist with referral as needed Review process manage expectations Ensure patient understands what must be established before they can begin first dose If disinterested, provide contact information and brief process instructions if interest arises later

58 Meeting with patients on PrEP Ask patient how their experience on PrEP has been- any barriers? Assess adherence When was your last missed dose? Reiterate why adherence is important Discuss patient sexual encounters Have encounters changed? Counsel patient on sexual health goals Meeting with patients after medical visits Address visit and concerns, discuss any gaps in patient understanding Providers can request discussion certain topics Adherence, sexual health counseling, substance use Counsel patients who are weighing their PrEP timeline How do you see your PrEP use moving forward?

59 Creating PrEP process in clinic Ensure established plan Discussions agency-wide, between and within disciplines Ensure buy-in; address discontent and disagreement Refer to mission, public health focus to remember shared goals Clearly state protocol, expectations and roles Flexibility: test and change plan as needed If feasible, appoint a point person for PrEP Troubleshoot implementation issues, manage crises: go-to person Institute change process when needed and provide feedback

60 General protocol goals Establish as patient Ensure HIV negative Prescribe medication Schedule follow-up visits Provide interdisciplinary counseling as needed

61 Protocol barriers Manage patient expectations immediately Timeline for access Review procedure and why each step necessary Remind of end goals Availability providers Scheduling challenges for new patients Scheduling challenges for employed patients Provider visit access Medication access Insurance

62 Insurance categories Medicaid Commercial/employer plan Marketplace plan (Obamacare) Medicare Uninsured

63 Prohibitive medication co-pays Truvada co-pay assistance Through Gilead, covers up to $300 per fill; max $3,600 per year If still high after co-pay assistance: Refer to Patient Assistance Network (PAN) Up to $4,000 per year Must meet income & insurance eligibility criteria Medical-necessity/code dependent If co-pay still prohibitive: Consider and counsel on alternative insurance options Patient may need to wait until next open enrollment Cost-benefit analysis of wait Assess eligibility for Medication Assistance Program through Gilead

64 PrEP-AP: Through NYSDOH/ADAP Uninsured patients unable to access insurance Goal of transition to insurance Medicaid Marketplace exchange plan (Obamacare) Employer plan Only PrEP access resource for undocumented individuals Eligibility criteria: similar to ADAP, must be proven Income < $51,200 annually Assets < $25,000 New York State Residency and HIV negative

65 PrEP-AP coverage Extremely limited: NOT primary care coverage PrEP protocol services covered: Visits, laboratory tests, STI screening and treatment Ideal to transition to insurance if able Provide free/sliding scale clinic resources Discuss program capabilities and reinforce limitations Utilize a contract as a guide for conversation Example: The Pre Exposure Prophylaxis Assistance Program (PREP-AP) Patient Agreement Form Utilized at the Mt. Sinai Institute for Advance Medicine s Spencer Cox Clinic

66 The Pre Exposure Prophylaxis Assistance Program (PREP-AP) Patient Agreement Form The Pre-Exposure Prophylaxis Assistance Program (PREP-AP) is a program administered by the New York State Department of Health that helps uninsured or underinsured individuals access required medical care for PrEP. The PrEP-AP covers limited services including medical appointments required for PrEP and certain laboratory tests. A complete list of these services is located on the PrEP-AP Services Handout. Your social worker will review this Agreement Form with you to ensure that you understand PrEP-AP. If you have any questions please contact the clinic at PrEP-AP only covers blood draws, and medical visits related to PrEP services which are listed on PrEP-AP Services Handout. If I receive medical services beyond those listed in the PrEP-AP Services Handout, I will receive a bill for those services. Should this occur and I cannot afford to the bill I may be eligible for assistance through the Hospitals HEAL Center. To obtain needed medications I will be enrolled in the Gilead Medication Assistance Program. This Medication Assistance Program will only provide the medications I need for PrEP. I will receive a PrEP-AP card upon enrollment in this program. It is my responsibility to show this card at the front desk every time I come for a PrEP visit to help the clinic know what I am coming in for. I will adhere to the PrEP-AP visit schedule. This includes three visits in the first month for which will involve blood testing, education, and provide me with an opportunity to ask questions or raise concerns. When the blood tests come back and the clinic deems PrEP safe for me to take, I will receive prescriptions for the medications and will attend medical visits every 3 months for monitoring. I will contact clinic staff if I experience any side effects that might be caused by taking PrEP. Testing and treatment for side effects may be covered by PrEP-AP on a case by case basis. I,, have reviewed the PrEP-AP Services Handout and I understand the information that was presented to me in this agreement. Please confirm your receipt of this agreement by signing below: Patient Signature: Date: Staff Signature: Date: May 1, 2015

67 The Truvada for PrEP Medication Assistance Program - Gilead Uninsured Medication caps No prescription coverage Used in conjunction with PrEP-AP Challenges Eligibility criteria Mail-order requirement Covance Pharmacy Communication challenges

68 PrEP-AP and Truvada-AP protocol Documented negative HIV test Access to free rapid testing Complete application Once approved, complete first visit with labs At second visit after results, Truvada rx Apply: Truvada for PrEP Medication Assistance Program Arrange for medication shipment

69 QUESTIONS?

70 Acknowledgements Chris Ferraris, LMSW Emily Gertz, MPH Emma Kaywin Mt. Sinai Institute for Advanced Medicine Spencer Cox Center

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72 IMPLEMENTATION OF PREP IN HEALTH CARE SETTINGS: A CASE BASED DISCUSSION Jeffrey Kwong, DNP, MPH,ANP-BC, FAANP Assistant Professor, Columbia University School of Nursing Gotham Medical Group

73 DISCLOSURE I have no relevant disclosures

74 LEARNING OBJECTIVES: 1. Describe types of patients who may benefit from PrEP 2. Discuss the challenges in managing patients on PrEP in various practice settings 3. Describe organizational considerations for providing PrEP

75 Case 1: RT 38 y.o. AA male CC: I had a slip up. HPI: Reports having unprotected receptive sex with a new partner who said he was clean. Concerned about HIV, last test was 3 months ago PMH: Anxiety Medications: Alprazolam 0.5 mg BID PRN

76 CASE 1 - CONTINUED Risk history 8 partners in the preceding 3 months Meets partners through Apps Treated 3 months ago for rectal and pharyngeal GC Uses condoms regularly

77 CASE 1 How would you handle this situation? What additional information do you want to know? Partner was anonymous Ejaculation occurred No rectal bleeding or ulcers Incident occurred about 8 hours ago

78 CASE 1 Is he a candidate for PrEP today?

79 Non-Occupational PEP (npep) Used to reduce or minimize risk of HIV infection following a high-risk exposure Should be administered within 36 hours of exposure* Duration of treatment is 28 days

80 Source: NYS AIDS Institute npep Guidelines, 2014

81 npep Laboratory Testing HIV testing GC/CT screening RPR or FTA-AB Hepatitis B & C serologies Source: NYS AIDS Institute npep Guidelines, 2014

82 Case 1 (Cont d) The patient s baseline 4 th generation HIV test was NEGATIVE. He tolerates npep without issues What should you do now?

83 CANDIDATES FOR PREP PrEP is indicated for HIV negative individuals who are at ongoing high risk for HIV infection. Potential Candidates for PrEP MSM who engage in unprotected anal intercourse Individuals who use stimulant drugs associated with highrisk behaviors, such as methamphetamine Individuals diagnosed with more than one anogenital sexually transmitted infection in the past year. Individuals who have been prescribed npep who demonstrate continued high-risk behavior or have used multiple courses of npep

84 Case 1 (cont) The patient tells you that although he uses condoms regularly, he would like to have that extra level of protection. He had excellent adherence with npep and tolerated it well without adverse side effect. You discuss continuing on TDF/FTC as PrEP.

85 HE DECIDES TO MOVE FORWARD BUT

86 COVERAGE & ACCESS Insurance carriers are covering PrEP Prior authorization required by most companies Truvada for PrEP Assistance Program Income requirements Medication shipped to provider s office Requires coordination between patient/pharmacy/provider

87 ICD CODES V01.79 (Z20.82) Contact or Exposure to other viral disease V01 (Z20.2) Contact with or exposure to communicable disease

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89 What other evaluation needs to be done at this point?

90 PRE-PRESCRIPTION ASSESSMENT CHECKLIST Screen for symptoms of acute HIV infection in last 6 weeks Review medication list Are there any potential interactions or synergistic toxicities? Assess mental health and substance use Explore patient knowledge of PrEP and Motivation for initiating medication Evaluate willingness to take DAILY PrEP Is the patient connected to primary care? Is patient involved with HIV positive partners? Are they on ARV Is there resistance data available? Screen for domestic violence Assess Housing Status Do they have the means to pay for PrEP? Evaluate fertility goals and contraception use in female PrEP Candidates

91 PRE-PRESCRIPTION LABORATORY EVALUATION New York State PrEP Guidance 2014

92 Laboratory Testing for npep Repeat HIV testing: 4 weeks and 12 weeks Monitor for signs/symptoms of Acute HIV infection (fevers, flu-like or mononucleosislike syndrome)

93 CASE 1: FOLLOW-UP Continued TDF/FTC (as PrEP) immediately after npep course completed Follow-up HIV testing as been negative Remained on PrEP for 3 months but then decided to discontinue due to decreased risk Remains HIV negative. Aware he can re-start PrEP again in the future.

94 CASE 2: SG 35 year old Latino male CC: My partner is HIV positive and I want to stay safe. HIV negative male in new relationship with partner who has HIV infection. Partner is on ART with undetectable viral load

95 CASE 2 - CONTINUED Report using condoms, but patient feels anxious about HIV infection. Never used npep, no previous history of STDs No other significant PMH Should he be offered PrEP?

96 US Public Health Service. (2014). Pre-Exposure Prophylaxis for the Prevention of HIV infection 2014: A clinical practice guideline.

97 Serodiscordant Couples For serodiscordant couples, suppressive ART for HIV-infected partner is a key factor Risk of transmission is low if HIV-infected partner is on suppressive ART with undetectable viral load

98 Meta-Analysis of Studies in Heterosexual Serodiscordant Couples Loutfy MR, Wu W, Letchumanan M, Bondy L, Antoniou T, et al. (2013) Systematic Review of HIV Transmission between Heterosexual Serodiscordant Couples where the HIV-Positive Partner Is Fully Suppressed on Antiretroviral Therapy. PLoS ONE 8(2): e doi: /journal.pone

99 HPTN 052 Evaluated the benefit of ART in prevention of sexual transmission of HIV-1 in serodiscordant couples (n=1763) Randomized to start ART immediately vs defer ART until CD cells/mm 3 or development of an AIDS-defining illness. Cohen MS, Chen YQ, McCauley M, et al. Prevention of HIV-1 infection with early antiretroviral therapy. N Engl J Med. 2011;365:

100 Cohen MS, Chen YQ, McCauley M, et al. Prevention of HIV-1 infection with early antiretroviral therapy. N Engl J Med. 2011;365: HPTN 052: Findings & Conclusion 39 seroconversions (35 in delayed arm, 4 in the immediate arm) 96% reduction in risk of transmission in the early treatment vs delayed treatment arm

101 PARTNER Study Observational study to assess risk of transmission in serodiscordant couples if HIV-infected partners has undetectable viral load. Recruited discordant couples who engaged in condomless sex (n=282 MSM; 445 heterosexual) PrEP was NOT used Rodger A, Bruun T, Cambiano V, et al. HIV transmission risk through condomless sex if HIV+ partner on suppressive ART: PARTNER study. Program and abstracts of the 21st Conference on Retroviruses and Opportunistic Infections; March 3-6, 2014; Boston, Massachusetts. Abstract 153LB.

102 PARTNER Study: HIV-uninfected partner reporting condomless sex % MSM Het Male Het Female % 70% % 30% 0 Vag Sex with Ejac Vag Sex Recep Anal Recep Anal with ejac Insert Anal Rodger A, Bruun T, Cambiano V, et al. HIV transmission risk through condomless sex if HIV+ partner on suppressive ART: PARTNER study. Program and abstracts of the 21st Conference on Retroviruses and Opportunistic Infections; March 3-6, 2014; Boston, Massachusetts. Abstract 153LB

103 PARTNER study: Findings & Implications No linked transmission occurred during eligible follow-up Estimated 10 year risk (derived from limit of 95% CI) suggests maximum of 4% overall, 10% for anal sex Rodger A, Bruun T, Cambiano V, et al. HIV transmission risk through condomless sex if HIV+ partner on suppressive ART: PARTNER study. Program and abstracts of the 21st Conference on Retroviruses and Opportunistic Infections; March 3-6, 2014; Boston, Massachusetts. Abstract 153LB.

104 New York State PrEP Guidelines PrEP is not meant to be used as a lifelong intervention, but rather as a method of increasing prevention during periods when people are at greatest risk of acquiring HIV. The length of use will depend on the individual s behaviors, which may change over time. (2014)

105 OTHER QUESTIONS TO CONSIDER Should PrEP be used indefinitely?

106 CASE 2 - CONTINUED Patient started PrEP Has been on PrEP for nearly 2 years Does not wish to stop Remains in monogamous relationship with HIV-infected partner Continues to come in periodically

107 CASE 3: VT 27 year old MSM CC: I want to start PrEP but my primary care doesn t know a lot about it. PMH: unremarkable Risk History: 6 partners in the past 3 months, mostly safe HIV negative 2 weeks ago

108 WHAT ARE THE BARRIERS TO PREP UPTAKE? Users Unaware of HIV risk, PrEP availability, or how to access it No or delayed access to clinical preventive care Uninsured or unable to pay Adherence challenges Concern about disclosure and stigma Providers Unaware of intervention Uncertain how to deliver the intervention Wary of complexity and time involved Discomfort with assessing candidacy Uncertain how to bill for intervention

109 PrEP Implementation: Prescriptions Jan Sep 2013 Mean age was 38.2 Males (39.5 ) Females (36.8) 12.3% under 25 years old % males under 25 = 8.0% % women under 25 = 16.8%

110 CONSUMER DEMAND FOR PREP Increasing awareness of PrEP may results in greater demand

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112 PREP UPTAKE Survey of online gay social networking site (n=9,179 men) 85.7% white, 3.9% Black, 7.5% Latino 58.7% reported unprotected anal sex 3.2% reported using npep, 1.2% reported PrEP use Although 84% had PCP, only 53.9% felt comfortable talking about MSM sex PrEP Users: More comfortable talking with provider about MSM sex. 16-fold greater odds of having used npep Mayer, et al. (2014). Early Adopters: Correlates of chemoprophylaxis use in an online sample of US Men who have sex with Men. CROI 2014 Abstrat 952

113 PREP UPTAKE Conclusions: In order to increase npep & PrEP among MSM, primary care providers should be educated to provide culturally competent care, so patients feel free to discuss HIV risks that could be decreased by npep or PrEP Mayer, et al. (2014). Early Adopters: Correlates of chemoprophylaxis use in an online sample of US Men who have sex with Men. CROI 2014 Abstrat 952

114 PREP UPTAKE: THE DEMO PROJECT 48 week demonstration project in SF and Miami (MSM & TF) 53% uptake (49% in SF and 64% in Miami) (386 enrolled out of 726 eligible participants) Correlates of uptake: Prior awareness of PrEP (AOR 2.3, 95% CI ) Unprotected anal sex with > 5 partners (AOR 1.8, 95% CI: ) > 1 episode of anal sex with HIV-infected partner (AOR 1.8, 95%CI ) Higher risk perception (AOR 1.9, 95% CI ) Cohen et al. (2014). Implementation of PreP in STD Clinics: High uptake and Drug detection among MSM in demonstration project. CROI Abstract 954

115 PREP ADHERENCE: THE DEMO PROJECT Sub-sample (n=87) had blood samples to test for presence of TFV-DP at 4 weeks Majority had evidence of taking at least 4 doses/week Cohen et al. (2014). Implementation of PreP in STD Clinics: High uptake and Drug detection among MSM in demonstration project. CROI Abstract 954

116 ..OTHER FACTORS

117 PROVIDER ATTITUDES & EXPERIENCE Survey of ID physicians (n=573) 74% supported PrEP 9% have actually prescribed PrEP 14% would not provide PrEP Karris et al. (2014). Clin Infec Dis 58(5)

118 PROVIDERS PERCEIVED BARRIERS TO PREP Cost of PrEP Drug Resistance Reluctance to start a toxic drug in a healthy person Efficacy of real world PrEP Time consuming Karris et al. (2014). Clin Infec Dis 58(5)

119 PROVIDERS CONCERN REGARDING PRESCRIBING PREP Tellalian et al. AIDS Patient Care and STDs. October 2013, 27(10):.

120 NO EVIDENCE OF RISK COMPENSATION IN IPREX STUDY Marcus et al. PLoS One 2013

121 Liu et al. (2015). dherence, sexual behavior and HIV/STI incidence among men who have sex with men (MSM) and transgender women (TGW) in the US PrEP demonstration (Demo) project

122 NPEP: LESSONS LEARNED

123 NPEP USE AND RISK BEHAVIOR Men who have sex with men from the EXPLORE trial M=4,295 participants (6.3% used npep during study) Conclusion: Availability of npep did not appear to lead to increased sexual risk Donnell, Mimiaga, et al. (2010). AIDS Behav 14:

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125 PROVIDER ATTITUDES & BELIEFS Most effective way to decrease acquisition of HIV infection? Expanded Testing Detection & treatment of STI Promotion of condom use Mental health & substance abuse counseling Community-based behavioral interventions PrEP Tellalian et al. AIDS Patient Care and STDs. October 2013, 27(10):.

126 PROVIDER KNOWLEDGE Survey of GW ID society & Armed Forced ID society MDs (n=105) 60% of knowledge questions answered incorrectly (higher knowledge in those with >25% of time doing HIV care) 67% felt current literature supports use of PrEP? Restrict prescribing PrEP to those with HIV experience Wilson et al. Knowledge and perception of PrEP in two cohorts of Infectious Disease providers. Poster. IDWEEK 2014 (1522)

127 Not correct! Courtesy: R. Peterson

128 PREP NY STATE GUIDELINES Follow-up and monitoring includes prevention services that are part of comprehensive prevention plan, such as: Risk reduction counseling Access to condoms STI screening Mental Health & Substance Use Screening, when indicated New York State Summary on Pre-Exposure Prophylaxis (2014).

129 CONSIDER TEAM-BASED APPROACHES

130 CHARACTERISTICS OF SUCCESSFUL PREP PROGRAMS Clinical Expertise Cultural competency Outreach Ongoing Quality Improvement Regularly provider training Comprehensive Needs Assessment Community/Consumer Involement Stakeholder Buy-In Engagement with Public Health System Sustainability Planning Infrastructure development Ongoing Quality Improvement Administrative management systems Fiscal Management systems Executive Leadership Support

131 CASE 4: AL 32 y.o. AA female who has HIV positive partner (undetectable viral load). Want to conceive as safely as possible. Cannot afford sperm washing. Is PrEP appropriate in this situation?

132 Pregnancy and risk of HIV infection Women are at increased risk of HIV infection during periods of trying to conceive with HIVinfected partner Mugo NR, Heffron R, Donnell D, et al. Increased risk of HIV-1 transmission in pregnancy: a prospective study among African HIV-1-serodiscordant couples. Aids. 2011;25(15): doi: /QAD.0b013e32834a9338.

133 Use of PrEP to prevent HIV during attempts to conceive PrEP should be discussed as one of several options to protect the uninfected partner during conception and pregnancy so that an informed decision can be made in awareness of what is known and unknown about benefits and risks of PrEP for mother and fetus (IIB) U.S. Public Health Service (2014) Prexposure prophylaxis for the prevention of HIV infection in the United States a clinical practice guideline

134 HIV infection and Conception: Options Sperm donor Treatment as prevention (TasP) Continuous PrEP Condoms and PrEP no condoms during fertile period Sperm Washing +/- intrauterine or in vitro fertilization DHHS. (2014) Recommendations for Use of Antiretroviral Drugs in Pregnant HIV-1-Infected Women for Maternal Health and Interventions to Reduce Perinatal HIV Transmission in the United States Bujan et al. (2007)AIDS, 21(14):

135 PrEP and Pregnancy If pregnant or becomes pregnant while on PrEP, discuss known risks and benefits of taking TDF/FTC during pregnancy After discussing the potential risks of TDF/FTC, recommend continuation of PrEP during pregnancy or breastfeeding for those with ongoing risk for HIV. U.S. Public Health Service (2014) Prexposure prophylaxis for the prevention of HIV infection in the United States a clinical practice guideline

136 For couples wishing to conceive Expert consultation is recommended so that approaches can be tailored to specific needs, which may vary from couple to couple (AIII). Partners should be screened and treated for genital tract infections before attempting to conceive (AII). The HIV-infected partner should attain maximum viral suppression before attempting conception (AIII). DHHS. (2014) Recommendations for Use of Antiretroviral Drugs in Pregnant HIV-1-Infected Women for Maternal Health and Interventions to Reduce Perinatal HIV Transmission in the United States

137 PrEPception Study Observational cohort study, which will test the feasibility and acceptability of PrEP for conception, while examining the challenges and generalizability of this current medical practice. Boston, Baltimore, San Francisco, Philadelphia

138 IMPLEMENTATION EXPERIENCE San Francisco 3 sites: Lessons Learned Accurate consumer knowledge is critical Patients risk perception and concern about side effects appear to play role in uptake, adherence, persistence Adequate capacity and sustainable delivery is critical Stigma can pose barrier to uptake and retention Liu et al. (2014) Early Experiences Implementing Pre-exposure Prophylaxis (PrEP) for HIV Prevention in San Francisco. PLoS Med 11(3): e

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141 Behavioral Interventions Improved Testing Treatment of HIV Biomedical Prevention End of AIDS 2020 Policy & Resource

142 SUMMARY AND KEY POINTS PrEP is a viable option for HIV prevention Organizations should assess capacity for providing PrEP including appropriate followup mechanisms, staff, and patient support systems Providers should become familiar with PrEP guidelines

143 SUMMARY AND KEY POINTS As consumer awareness of PrEP increases, providers should be prepared to offer accurate information and/or offer referrals to appropriate expertise Providers should continue to assess candidates for PrEP and offer, if appropriate

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146 QUESTIONS? Contact Information Jeffrey Kwong, DNP, MPH, ANP-BC

147 FROM PAIN TO PREP - ONE CONSUMER S JOURNEY Damon L. Jacobs, Marriage and Family Therapist

148 Disclosure Damon L. Jacobs has no financial relationships with commercial entities to disclose 2

149 LEARNING OBJECTIVES: 1.To recognize the variety of emotional factors that contribute to one s decision to use PrEP. 2. To understand limitations of traditional safersex messages with patients at risk for HIV. 3. To expand the concept of PrEP to include beneficial mental health outcomes.

150 Let s start at the very beginning

151 I could never quite fit in with the other kids 5

152 I started to realize I could be gay. Until this. 6

153 Finally I came out and went to college, where great things awaited 7

154 In the beginning, the condoms only message was all we had to offer. 8

155 Yet one by one, I knew friends, lovers, roommates, colleagues, coworkers, clients, who acquired HIV. Many passed away. This is my friend Nicolaas at age 25 in October, He died five months later. 9

156 I met Jhan Dean Egg in He was 28 at the time, and became a beloved roommate, friend, trusted ally 10

157 This is what I woke up to every day 11

158 And then I met Chris Bender in

159 Our connection continued to get stronger throughout the years 13

160 By 2005, New York was calling 14

161 I had a wonderful opportunity to participate in, and later work for, HVTN Trials. 15

162 Toward the end of 2010, we were all called into the office for an important announcement. 16

163 Shortly afterward, Chris died. This is the last picture taken of him on January 25, He was 53 years old. 17

164 I began using Truvada for PrEP on July 19,

165 The media began to take an interest in this new HIV prevention strategy.. 19

166 I honor the memories of the people I love who are gone, and those who are still here, by using PrEP daily and teaching others about it. 20

167 QUESTIONS?

168 Damon L. Jacobs, Marriage and Family Therapist FaceBook Group - PrEP Facts: Rethinking HIV Prevention and Sex