F/C AETC-Project ECHO ™

1. F/C AETC-Project ECHO™ Facilitator: Jennifer Janelle, MD University of Florida College of Medicine, Gainesville Faculty, Florida/Caribbean AETC

2. Case Discussants Jeffrey Beal, MD, AAHIVS Principal Investigator and Clinical Director Florida/Caribbean AETC Serenia P. Beckton, BA STD Program Manager Palm Beach County Health Department

3. Disclosure of Financial Relationships These speakers have no significant financial relationships with commercial entities to disclose. These speakers will not discuss off-label use or an investigational product during the program. This slide set has been peer-reviewed to ensure that there are no conflicts of interest represented in the presentation.

4. Goals of F/C AETC-Project ECHO™ • ECHO = Extending Community Health Outcomes • Provide clinical consultations through the use of case presentations in an informal co-management setting • Encourage longitudinal learning opportunities for participants by providing ongoing education and training opportunities • Develop an information support system for attendees

5. F/C AETC-Project ECHO™ • Educational experiences • Intended for novice to expert clinicians • Brief didactic presentations • Case presentations • Opportunity for networking • CME/CEU

6. F/C AETC-Project ECHO™ Session Format • Welcome and Introductions • 5 minutes • Overview of Important Points • 5 minutes • Brief Didactic Presentation • 10 minutes • Case Presentation(s) • 1 hour • Question/Answer Session • 10 minutes

7. Didactic Presentation Pre-exposure Prophylaxis for HIV Infection

8. iPrEx Trial • Enrolled 2499 HIV-seronegative men or transgender women who were at high risk for HIV acquisition • Trial of daily emtricitabine plus tenofovir (FTC-TDF) versus placebo.

9. Additional Interventions During the iPrEX Trial • Comprehensive prevention services • Monthly HIV-1 testing • Condom provision • Counseling • Management of other sexually transmitted infections • Testing and vaccination for hepatitis B if indicated

10. Kaplan–Meier Estimates of Time to HIV Infection (Modified Intention-to-Treat Population) 44% reduction in risk of HIV transmission in FTC-TDF group vs placebo Grant RM et al. N Engl J Med 2010;363:2587-2599.

11. Levels of Study-Drug Components in Blood of Subjects Receiving FTC–TDF, According to HIV Status Grant RM et al. N Engl J Med 2010;363:2587-2599

12. iPrEX Trial • Intensive risk reduction counseling led to decreased self-reported risk behavior • Increase in condom use • Decrease in number of sex partners

13. iPrEX Trial Conclusions • Oral FTC–TDF provided protection against the acquisition of HIV infection among the subjects. • Additional protection likely provided by intensive risk reduction strategies

14. Partners PrEP Trial • Enrolled 4758 HIV-1–serodiscordant heterosexual couples in Kenya and Uganda • Intervention: • Daily antiretroviral prophylaxis with tenofovir (TDF) or emtricitabine–tenofovir (FTC-TDF) vs placebo in the HIV-1–negative partner

15. Partners PrEP Trial: Enrollmentand Follow-up of the Study Participants Baeten JM et al. N Engl J Med 2012;367:399-410

16. Partners PrEP Trial • Risk reduction measures • HIV-1 testing with counseling before and after testing • Individual and couples risk-reduction counseling • Screening and treatment for sexually transmitted infections • Free condoms with training • Counseling and referral for male circumcision • Postexposureprophylaxis according to national policies

17. Kaplan–Meier Estimates of the Primary End Point in the Modified Intention-to-Treat Analysis, According to Study Treatment Relative Rate Reductions vsPlacebo: TDF 67% TDF-FTC 75% Baeten JM et al. N Engl J Med 2012;367:399-410

18. Partners PrEP Trial • Plasma drug levels measured in about 10% • Risk reduction appeared greatest in subjects with detectable plasma tenofovir level • Conclusion: Pre-exposure prophylaxis with TDF or FTC-TDF was effective in both men and women

19. FTC-TDF for PrEP • FTC-TDF (Truvada®) received FDA approval for PrEP in July 2012 • FDA indication: • FTC-TDF is indicated in combination with safer sex practices for pre-exposure prophylaxis (PrEP) to reduce the risk of sexually acquired HIV-1 in adults at high risk

20. PrEP: Who is High Risk? • Has partner known to be HIV-1 infected or • Engages in sexual activity within a high prevalence area or social network plus one of the following • Inconsistent or no condom use • Diagnosis of sexually transmitted infections • Exchanges sex for commodities (money, shelter, food, drugs) • Use of illicit drugs or alcohol dependence • Incarceration • Partner of unknown HIV-1 status with any of the above factors

21. FTC-TDF for PrEP • When prescribing FTC-TDF for PrEP, providers must do the following: • Prescribe FTC-TDF as part of a comprehensive prevention strategy • Counsel all uninfected individuals to strictly adhere to the recommended daily FTC-TDF dosing schedule

22. FTC-TDF for PrEP • Confirm a negative HIV-1 test immediately prior to initiating PrEP.If clinical signs or symptoms consistent with acute viral infection are present and recent (<1 month) exposures are suspected, • delay starting PrEP for at least 1 month and reconfirm HIV-1 status or • use a test approved by the FDA as an aid in the diagnosis of HIV-1 infection, including acute or primary HIV-1 infection

23. FTC-TDF for PrEP • HIV-1 screening tests should be repeated at least every 3 months • If symptoms consistent with acute HIV-1 infection develop following a potential exposure event, PrEP should be discontinued until negative infection status is confirmed using a test approved by the FDA as an aid in the diagnosis of HIV-1, including acute or primary HIV-1 infection

24. FTC-TDF PrEP Safety Issues • Can cause new onset or worsening renal impairment • Assess creatinine clearance (CrCl) before prescribing FTC-TDF • Do not start if CrCl < 60 mg/mL • Assess risk/benefit if renal function declines • Routinely monitor CrCl and serum phosphorus • Avoid with concurrent or recent use of nephrotoxic drugs TRUVADA [package insert]. Foster City, CA: Gilead Sciences, Inc; 2012.

25. FTC-TDF PrEP Safety Issues • Decreases in bone mineral density • Redistribution/accumulation of body fat • Hepatitis B infection • Pregnancy • Common adverse drug reactions in more than 2% of subjects in clinical trials • Headache, abdominal pain, decreased weight TRUVADA [package insert]. Foster City, CA: Gilead Sciences, Inc; 2012.

26. Available Resources for FTC-TDF for PrEP • Agreement form signed by healthcare provider and patient • Used to document the discussion of the benefits/risks of FTC-TDF for PrEP • Pharmaceutical patient assistance program • More information and forms available online

27. http://www.univhc.com/docs/Medicaid/Forms/HIV-HEP-B_Diagnosis_Verification_Form.pdfhttp://www.univhc.com/docs/Medicaid/Forms/HIV-HEP-B_Diagnosis_Verification_Form.pdf

28. Case presentationS

29. Case – JD Patient JD is a 32 y/o white male HIV negative partnered for 12 years with your other patient DY who is his 40 y/o HIV positive male partner. JD prefers receptive anal sex and reports on a rare occasion they have had a condom break. His partner enjoys but does not wish to perform penile-anal sex for fear of infecting JD and it is a serious issue in the relationship. JD has read since DY is undetectable on HIV VL there is a marked decrease in his risk of his becoming infected.

30. Case – JD DY has been through multiple ARV regimens since initially infected 25 years ago. He has NRTI/NNRTI and PI resistance mutations. Currently controlled on DRV/r, ETR, and TDF/FTC FDC. In the last year DY has had 2 blips neither of which have exceeded 400 copies/mL. He always reports 100% compliance but does admit to an occasional partner outside the relationship which JD does not know and he refuses to tell. He is HBV immune and HCV negative. DY is otherwise healthy.

31. Case - JD JD is faithfully monogamous with DY, is immune to HBV, negative for HCV, and admits to snorting cocaine ‘at times’ and states he likes to smoke THC before sex. He convinced DY to have sex with him 2 weeks ago without a condom but DY refuses to do this again which JD finds unacceptable and inconsiderate of his needs. They cannot afford counseling services.

32. Identify the issues in this case. What therapeutic options do you recommend?

33. Case - 2 • 24 yo man presents to your clinic for routine healthcare. He has a history of sex with multiple female and male partners (more than 25 partners/year). His last high risk, unprotected sexual encounter was 18 days ago.

34. discussion

35. Markers of HIV Infection and Windows of Detection P. Patel et al. / Journal of Clinical Virology 54 (2012) 42– 47

36. 4th Generation HIV Test • Combined antibody and antigen test • Detects p24 antigen which is present soon after infection and prior to the development of antibody • Can detect acute HIV infection which can lead to • Earlier linkage to care • Earlier initiation of therapy • Decreased transmission within networks

37. HIV Testing Algorithm J ClinVirol. 2011 Dec;52 Suppl 1:S35-40. Epub 2011 Oct 21.

38. Questions?