1. HIV Prevention 2016 John Leander Po, MD, PhD
Infectious Disease Fellowship Program Director
Associate Professor of Clinical Medicine
University of Arizona
Cesar Egurrola, Clinical Coordinator
Petersen HIV Clinics

2. Special thanks: Mayar Al Mohajer, MD FACP
Medical Director, Antibiotic Stewardship Program
Associate Professor of Clinical Medicine
University of Arizona

3. Disclosures AETC- PEP & PrEP
I have no financial relationships to disclose.
PrEP Navigator Model discussed in this presentation is specific to the Navigator component and experiences at Petersen HIV Clinics.

4. Michael
You are evaluating a 23 year-old male at your office for a primary care visit
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

5. What would you recommend for Michael?
HIV screening
HIV and STD screening
HIV, STD screening and discuss the importance of persistent condom use
Offer daily Truvada (TDF/FTC) plus HIV, STD screening and discuss the importance of consistent condom use

6. Understanding PrEP Example: Birth Control Pill 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)

7. If PrEP is taken daily, it can reduce sexually acquired HIV infection by up to…
50-60%
60-80%
80-90%
>90%

8. I feel that patients on PrEP will…
Increase their risk behavior
Decrease their risk behavior
No change in behavior
I don’t know

9. Which statement best applies to you?
I have not prescribed PrEP
I have prescribed PrEP for 1-5 patients
I have prescribed PrEP for >5 patients

10. For those who said they have not prescribed PrEP, was it because…
I need more information about PrEP
It takes too much time
None of my patients could afford it
Other

11. My top concern about PrEP is…
Not enough research on long term effects of PrEP
Financial concerns – who is paying for it?
STDs will increase due to increase in risk behavior
Patients will not be adherent
Not enough education for providers
On demand PrEP is not effective in women
Other
Top 2 concerns? How does the audience choose 2?

12. Only Infectious Disease Specialists can prescribe anti-viral medications
True
False
Don’t know

13. PrEP Navigators
Individuals based out of provider’s office or community organizations linked to providers, whose main role is to facilitate access to PrEP.
PrEP navigation is “A comprehensive and system-wide approach is necessary to ensure that HIV-negative persons at risk of being exposed to HIV are effectively linked to and managed on PrEP”- California Department of Public Health
-People interested on PrEP need additional information about it, and other prevention methods, in order to decide whether PrEP is an option they want to pursue.
-PrEP Navigator used as an unofficial term. Different PrEP programs define navigator’s role differently, but all among the same lines: to provide patients with the support they need to access PrEP.
-California DPH officially put out a RFA (request for application) for PrEP Navigators at the begging of 2016.

14. PrEP Navigators Provides basic PrEP Information and education
Locate, and sometimes link to PrEP Providers
Teaches patients how to utilize public and private insurance to access PrEP (insurance navigation)
Explains and explores Patient Assistance programs for Truvada
Helps uninsured or underinsured patient navigate insurance options
Links to community based clinic if uninsurable
-typically PrEP navigators are the first point of contact for people interested in PrEP.
-A PrEP Navigator should be able to answer all initial PrEP questions (or provide guidance), as well as paint a clear picture of the PrEP care process
Navigator is first point of contact, and provide the information needed for patients to have a better understand of PrEP so that they can be better prepared for first medical apt.

15. PrEP Navigator- Education
Provide accurate information about PrEP intervention based on CDC PrEP Guidelines.
Review PrEP care process.
Provide PrEP education around importance of adherence to medication and PrEP care plan, as well as follow ups.
Empower patient to self advocate for PrEP care as needed.
Answer any questions concerns patient might have before starting PrEP
Key messages- Adherence is key!
Communication w provider highly encouraged.

16. How does PrEP work?

17. Pre-Exposure Chemoprophylaxis for HIV Prevention in Men Who Have Sex with Men- The iPrEX Trial
Randomized clinical trial 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
Grant RM, et al. N Engl J Med 2010;363:

18. Grant RM et al. N Engl J Med 2010;363:2587-2599.
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:

19. Sexual behavior by perceived treatment group
Marcus JL, Glidden DV, Mayer KH, Liu AY, et al. (2013) No Evidence of Sexual Risk Compensation in the iPrEx Trial of Daily Oral HIV Preexposure Prophylaxis. PLoS ONE 8(12): e doi: /journal.pone

20. Antiretroviral Prophylaxis for HIV Prevention in Heterosexual Men and Women- The Partners-PrEP Trial
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
Baeten JM et al. N Engl J Med 2012;367:

21. On-Demand Preexposure Prophylaxis in Men at High Risk for HIV-1 Infection
Randomized clinical trial- 414 subjects
Truvada (TDF/FTC) before and after sexual activity was shown to decrease the risk of HIV transmission by 86% in MSM who also received comprehensive preventive services
Median of 15 pills/ month
Molina JM, et al. N Engl J Med 2015; Dec 3;373(23):

22. FDA Approval

23. Indications:
On 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:
HIV-positive partners
MSM with recent unprotected sex or STD
Intravenous drug users (IDU) who reported sharing needles or equipment, or have recently starting substance use treatment program (high-risk for relapse).
Heterosexual men or women who infrequently use condoms and have sex with high-risk partners

24. Estimated percentages and numbers of adults with indications for preexposure prophylaxis (PrEP), by transmission risk group — United States, 2015
1 in 4
1 in 5
1 in 200
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, Morbidity and Mortality Weekly Report, 64(46);

25. Case Continued: You decided to start Michael on PrEP
Case Continued: You decided to start Michael on PrEP. What tests should you order next?
HIV testing, hepatitis B antigen and Cr clearance
HIV testing, CD4, liver function test and Cr clearance
HIV testing, liver function testing, and Cr clearance
HIV testing, CD4 and liver function testing

26. Testing
HIV testing, hepatitis B antigen and Cr clearance are key tests before starting PrEP
Other tests include:
STD panel (RPR, GC/CD)
Hepatitis A serology in MSM (for immunity)
Hepatitis B serology (for immunity)
Hepatitis C serology
Pregnancy testing (in women)

27. How often should you repeat HIV testing?
Every 30 days
Every 3 months
Every 6 months
Once a year

28. Re-confirm negative HIV-1 status at least every 3 months
Are there signs or symptoms of HIV-1 infection, OR is recent exposure to HIV suspected? No
Yes
Confirm that HIV-1 has not been contracted using a highly sensitive, FDA-approved test. If appropriate, consider prescribing PrEP
Do not initiate PrEP. Wait 1 month to ensure HIV-1 has not been contracted. or
Confirm negative HIV-1 status. If appropriate, consider prescribing PrEP.
Re-confirm negative HIV-1 status at least every 3 months

29. Reducing HIV Risk Behaviors
Trusting and confidential environment
Ongoing dialogue with the patient regarding their risk behavior
PrEP is not always effective in preventing HIV infection particularly if used inconsistently
Consistent use of PrEP together with other prevention methods (consistent condom use, discontinuing drug injection or never sharing injection equipment) confers very high levels of protection

30. PCH- Risk Factor Breakdown
Risk factor at intake, self reported by patient.

31. Beginning PrEP Medication Regimen
Prescribe 1 tablet of Truvada (TDF [300mg] plus FTC [200mg]) daily.
In general, prescribe no more than a 90-day supply, renewable only after HIV testing confirms that patient remains HIV-uninfected.
Provide risk-reduction and PrEP medication adherence counseling and condoms.

32. PrEP Navigator- Benefits Coordination
Provide patient with estimate on PrEP cost, based on their insurance plan
Benefits Summary (medical visits, lab work)
Formulary (medication)
Find providers who work with patient’s specific insurance plan
Assist patient with prior authorization and appeals if necessary.
Link patient to PAP if necessary.

33. Case Continued: Michael (without PrEP Navigator)
Michael goes to his local pharmacy to fill his prescription. The pharmacist tells him he has $500 copay. Michael cannot afford this copay. What do you think Michael will do next?
Call Native Health and leave a message for his provider letting them know he cannot afford his prescription
Put the co-pay on his credit card
Nothing. Michael’s PrEP journey ends at the pharmacy
Other

34. Michael: Case Continued (with Navigator)
Prior to going to the pharmacy, Michael speaks with the Native Health PrEP navigator who educates him on patient assistant options. When he goes to his local pharmacy , the pharmacist tells him he has $500 copay. Michael cannot afford this copay. What do you think Michael will do next?
Self advocate – talk to pharmacist about patient assistance options
Call navigator for assistance.
Access patient assistance option on his own.
Go to a different pharmacy recommended by Native Health
Other

35. Truvada Patient Assistance- GILEAD’s co-pay card
Works with commercial insurance plans only and covers co-pays for medication.
Federal insurance plans, such as Medicare, Medicaid, VA, Tricare or Federal Employee Health Plans are not eligible.
Covers $3,600 maximum per calendar year.
No income restrictions.
Yearly enrollment required.
Covers co-pays, deductible and coinsurance.
To apply visit or call
Easiest PAP to access, immediate approval for those who qualify.
Application takes about 5 minutes, once approved get information to provide to pharmacy (BIN, PCN, group and ID) pharmacy can run this as secondary insurance.
Pharmacies should be familiar w copay cards and can instantly activate for pt.

36. Truvada Patient Assistance- GILEADS’s Advancing Access
Works with commercial insurance plans only.
Federal insurance plans, such as Medicare, Medicaid, VA, Tricare or Federal Employee Health Plans are not eligible.
Covers the whole amount of medication co-pay.
Income based program, recipients income must be less than 500% FPL (<$59,400/year).
Application, with provider signature, required.
Proof of Income and Proof or Residency required with application.
Re-apply as needed.
Covers co-pays only.
To apply visit or call
Main different from co-pay card: it covers more (all of your co-pays, even if they exceed $3,600 per year), but it has an income limit for eligiility.
Not instant approval (can take 1-2 business days once full application and supporting documents are turned in).

37. Truvada Patient Assistance- Patient Advocate Foundation (PAF)
Works with all insurances
Covers $5,000 maximum per year.
Income based programs, recipient’s income must be less than 400% FPL (<$47,520/year).
Re-apply as needed.
Covers co-pays only.
To apply visit or call
Mention Patient Access Network Foundation- currently closed for PrEP assistance.
PAF reimburses for copays. Either patient will have to pay up front and submit receipts for reimbursement, or a willing pharmacy can provide medication to patient and submit co-pays for reimbursement.
Only medication support program for federal insurance plans such as Medicare or Medicaid

38. Provider-Pharmacy Collaborations
Encouraged for adherence and easier access to medication
Provider identifies two or more pharmacies and forge a collaboration for easier access to Truvada
Increased communication
Faster access to medication
Increased adherence

39. CDC Guideline: Follow-up and Monitoring
At Least Every 3 Mos
After 3 Mos and at Least Every 6 Mos Thereafter
At Least Every 6 Mos
At Least Every 12 Mos
All patients
HIV test
Medication adherence counseling
Behavioral risk reduction support
Adverse event assessment
STI symptom assessment
Assess renal function
Test for bacterial STIs
Evaluate need to continue PrEP
Women
Pregnancy test (where appropriate)
HBsAg+
HBV DNA by quantitative assay* (every 6-12 mo)
CDC. PrEP Guideline. 2014

40. PrEP in Clinical Practice: What Are the Barriers to PrEP Uptake?
Users
Providers
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
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

41. PHC- PrEP Insurance Breakdown
As of September N= 64
Most of our patients take advantage of PAP for Truvada, and pay $0.00 out of pocket for it.

42. Stopping PrEP Reasons to stop PrEP: Evidence of HIV infection
Pregnancy
Adverse events
Chronic non-adherence
Patient choice
On Discontinuing PrEP: Hepatitis B antigen, HIV
If resuming PrEP after stopping, repeat standard pre-PrEP evaluation

43. On-Demand Preexposure Prophylaxis in Men at High Risk for HIV-1 Infection
Randomized clinical trial- 414 subjects
Truvada (TDF/FTC) before and after sexual activity was shown to decrease the risk of HIV transmission by 86% in MSM who also received comprehensive preventive services
Median of 15 pills/ month
Molina JM, et al. N Engl J Med 2015; Dec 3;373(23):

44. Future directions of PreP
Why single dosing of PreP is not effective in women?
Other drug delivery systems
Alternative antiretrovirals for PreP

45. Women: Single dose PreP not as effective
Garrett KL, and others, CROI 2016, Boston, MA

46. Women might need to be more adherent than MSM
Percent of Women Achieving Effective Drug Concentrations in CD4+ Cells
Pharmacokinetics in 49 healthy female volunteers
Rectal Tissue
Female Genital Tract Tissue
2-7 doses/week (28% adherence) protects colorectal tissue
6-7 doses/week (85% adherence) to protect female genital tract tissue
Cottrell ML et al, J Infect Dis 2016

47. Single dosing of TDF: not enough drug in CVF
Garrett KL, and others, CROI 2016, Boston, MA

48. New data on PrEP
MTN-020/ASPIRE & IPM-027: Efficacy and Safety of Dapivirine Vaginal Ring. Protection 27-37%
ÉCLAIR: Cabotegravir LA (injectable) in HIV-Negative Men at Low Risk for HIV Infection
HPTN-069/A5305: Maraviroc-Based PrEP for MSM

49. PrEP Start-Up Kit
Created by PHC staff to provide support for providers interested in starting PrEP care at their practices. It includes:
PrEP Provider Guide (AETC)
PrEP intake form (PHC)
PrEP Flow Chart (Project Inform)
Medication Assistance Program Application(GILEAD)
AETC can provide clinical guidance and technical support for Providers wanting to start PrEP.

50. 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
Patient assistance options are available to help patients afford PrEP.
Patients prescribed PrEP should return for follow-up visits at least every 3 months

51. Questions

52. Training Evaluation Please complete an online evaluation, at:

53. Josh
Josh is a 28-year-old male who is presenting to your office for an urgent visit
He reported that he was having sex with a guy the night before without a condom (insertive anal)
He is concerned that the guy has not been tested for HIV before
Josh was tested for HIV three months ago and the result was negative
He uses condoms most of the times except when he drinks alcohol

54. What is the best next step?
Avoid prescribing PEP since the patient did not have unprotected receptive anal intercourse
Place a STAT order for infectious disease consultation so the patient can be seen within a week
Prescribe PEP immediately
Repeat HIV testing in 2 weeks (window period). If test is negative, then prescribe PEP

55. Exposure Risks (average, per episode, involving HIV-infected source patient)
Percutaneous (blood)
Mucous membrane exposure
0.3%
0.09%
Receptive anal intercourse %
Insertive anal intercourse
0.06%
Receptive vaginal intercourse
0.1 – 0.2%
Insertive vaginal intercourse
0.03 – 0.14%
Receptive oral (male)
Female-female orogenital
4 case reports
IDU needle sharing
0.67%
Vertical (no prophylaxis)
24%
1. Bell DM. Am J Med 1997;102(suppl 5B):9--15.
2. Ippolito G et al. Arch Int Med 1993;153:
3. Am J Epidemiology 1999;150:
4. Am J Epidemiology 1999;150:
5. MMWR 47;RR-17, 1998.
6. NEJM 336(15): (rates in Europe & U.S.)
7. Am J Epidemiology 1999;150:
8. Rothenberg RB et al. AIDS 1998;12:
9. MMWR 47;RR-17, 1998.
10. ACTG 076

56. Risk of Infection Blood and visibly bloody body fluids
Semen, vaginal secretions, cerebrospinal fluid, synovial fluid, pleural fluid, peritoneal fluid, pericardial fluid, and amniotic fluid
Feces, nasal secretions, saliva, sputum, sweat, tears, urine, and vomitus are not considered potentially infectious unless they are visibly bloody

57. Initiating PEP
If the decision is made to administer post-exposure prophylaxis, it should be started as early as possible after an exposure, ideally within 2 hours
Post-exposure prophylaxis is not indicated if the patient presents for care more than 72 hours after an exposure
HIV testing (serology and RNA) should be performed at baseline
Before offering post-exposure prophylaxis, patients should also be evaluated for the following criteria:
the nature of the exposure
whether the HIV status of the source is known
whether the exposure occurred within 72 hours prior to presentation
whether the patient is committed to future risk reduction
New York State Department of Health Guidelines 2014

58. What is the recommended PEP regimen?
Zidovudine/lamivudine plus boosted darunavir
Tenofovir/emtricitabine plus raltegravir
Tenofovir/emtricitabine
Zidovudine/lamivudine plus boosted lopinavir

59. Tenofovir + emtricitabine [Truvada] (QD) plus either raltegravir (BID) or dolutegravir (QD) are recommended as the preferred initial PEP regimen because of:
its excellent tolerability
proven potency in established HIV infection
ease of administration
Zidovudine and efavirenz are no longer recommended in the preferred PEP regimen because of significantly high rates of treatment-limiting side effects

60. PEP treatment should be continued for __days
PEP treatment should be continued for __days. HIV testing should be repeated at __ weeks and __ months.
28 days; 4 weeks and 3 months
28 days; 4 weeks and 6 months
42 days; 4 weeks and 3 months
42 days; 4 weeks, and 6 months