1. PrEP and My Patients: Guidance for LGBT Community–Based Primary Care Providers on Novel Strategies to Reduce Risk of HIV Acquisition This program is supported by an educational grant from

2. clinicaloptions.com/hiv PrEP and My Patients About These Slides  Our thanks to the presenters who gave permission to include their original data  Users are encouraged to use these slides in their own noncommercial presentations, but we ask that content and attribution not be changed. Users are asked to honor this intent  These slides may not be published or posted online without permission from Clinical Care Options (email permissions@clinicaloptions.com) Disclaimer The materials published on the Clinical Care Options Web site reflect the views of the authors of the CCO material, not those of Clinical Care Options, LLC, the CME providers, or the companies providing educational grants. The materials may discuss uses and dosages for therapeutic products that have not been approved by the United States Food and Drug Administration. A qualified healthcare professional should be consulted before using any therapeutic product discussed. Readers should verify all information and data before treating patients or using any therapies described in these materials.

3. clinicaloptions.com/hiv PrEP and My Patients Faculty Who Contributed to This Program Jared M. Baeten, MD, PhD Associate Professor Department of Global Health and Medicine University of Washington Seattle, Washington Susan Buchbinder, MD Associate Clinical Professor Departments of Medicine, Epidemiology, and Biostatistics University of California, San Francisco Director, HIV Research Section San Francisco Department of Public Health San Francisco, California

4. clinicaloptions.com/hiv PrEP and My Patients Faculty Who Contributed to This Program (cont’d) Albert Liu, MD, MPH Assistant Clinical Professor Department of Medicine University of California, San Francisco Director, HIV Prevention Intervention Studies HIV Research Section San Francisco Department of Public Health San Francisco, California Connie Celum, MD, MPH Professor, Department of Global Health and Medicine University of Washington Seattle, Washington

5. clinicaloptions.com/hiv PrEP and My Patients Disclosures Jared M. Baeten, MD, PhD, has no significant financial relationships to disclose. Susan Buchbinder, MD, has no significant financial relationships to disclose. Connie L. Celum, MD, MPH, has no significant financial relationships to disclose. Albert L. Liu, MD, MPH, has no significant financial relationships to disclose.

6. Antiretroviral Therapy for Preventing HIV Acquisition: Available Data and Ongoing Trials

7. PrEP Background

8. clinicaloptions.com/hiv PrEP and My Patients Prior to exposure Time of transmission After infection Advantages  Shorter course than PrEP Challenges  Limited data  Recognition of risk  Initiation < 48 hrs  Adherence  Public health impact Advantages  Clinical benefits and reduced infectiousness Challenges  Scale up; resources  Long-term adherence  Long term toxicity  Resistance Advantages  Demonstrated efficacy Challenges  Adherence  Delivery  Cost-effectiveness  Resistance PrEPPEPART Using Antiretroviral Medications for HIV-1 Prevention

9. clinicaloptions.com/hiv PrEP and My Patients Tenofovir for PrEP  Completed clinical trials of PrEP have tested tenofovir –Oral TDF, oral TDF/FTC, vaginal gel  Potent: rapid antiretroviral activity  Safe: Substantial treatment safety experience  Easy: Once-daily dosing, few drug-drug interactions  Evidence that concept should work –Animal models and postnatal prophylaxis of breastfeeding infants showed high levels of protection

10. Breakthroughs in PrEP

11. clinicaloptions.com/hiv PrEP and My Patients iPrEx: Eligibility  Male sex at birth (N = 2499)  18 yrs of age or older  HIV-seronegative status  Evidence of risk for acquisition of HIV infection Grant RM, et al. N Engl J Med. 2010;363:2587-2599.

12. clinicaloptions.com/hiv PrEP and My Patients iPrEX Study Sites Lima Iquitos Guayaquil Sao Paulo Rio de Janeiro Boston San Francisco Cape Town Chiang Mai Sites11 Participants2499 Grant R, et al. CROI 2011. Abstract 92. 56% 15% 12% 9% 5% 4%

13. clinicaloptions.com/hiv PrEP and My Patients iPrEx: Baseline Demographics Characteristic, % Overall (N = 2499) Age  Younger than 25 yrs 50  25-39 yrs 40  40 yrs or older 10 Race  White 17  Black 9  Asian 5  Mixed/other 69  Latino 72 Completed some college 43 Grant RM, et al. N Engl J Med. 2010;363:2587-2599.

14. clinicaloptions.com/hiv PrEP and My Patients iPrEx: Efficacy  Efficacy through study end (mITT): 42% (95% CI: 18% to 60%) P =.002 Placebo FTC/TDF Cumulative Probability of HIV Infection 0.12 0.10 0.08 0.06 0.04 0.02 0 14401224364860728496108120132 Wks Since Randomization Pts at Risk, n Placebo FTC/TDF 12481198115711199327866385284333442391030106 12511190114911099398086515234193452531034116 Grant R, et al. CROI 2011. Abstract 92.

15. Challenges of PrEP

16. Drug Resistance

17. clinicaloptions.com/hiv PrEP and My Patients iPrEx: Breakthrough Infections and Resistance  New HIV infections (91 samples tested) [1] –No drug resistance in participants on FTC/TDF –2 with minor variant drug resistance on placebo (1 to TDF, 1 to FTC)  HIV infections already present at enrollment –2 cases of FTC resistance in FTC/TDF arm [2] –Resistance dropped to undetectable levels within 6 mos after stopping PrEP [1] 1. Liegler T, et al. CROI 2011. Abstract 97LB. 2. Grant RM, et al. N Engl J Med. 2010;363:2587-2599.

18. Safety and Tolerability

19. clinicaloptions.com/hiv PrEP and My Patients iPrEx: Adverse Events  No significant differences in adverse events between arms Adverse EventFTC/TDF (n = 1251) Placebo (n = 1248) P Value %Events% Any grade 3/4 event 1224813285.51 Death < 11 4.18 Serious adverse event 576587.57 Elevated creatinine 228115.08 Creatinine elevation confirmed on next visit 0.47.000.06 Grant R, et al. CROI 2011. Abstract 92.

20. clinicaloptions.com/hiv PrEP and My Patients iPrEx: BMD Changes and Fracture Rates  BMD changes were small (~1%); no evidence of negative effect on health [1]  No differences in fracture rates between groups [1,2]  All fractures were trauma related  Need longer follow-up to evaluate effects on bone density and fracture risk over time 1. Liu AY, et al. Plos One. 2011;6:e23688.2. Grant RM, et al. N Engl J Med. 2010;363:2587-2599.

21. clinicaloptions.com/hiv PrEP and My Patients iPrEx: Nausea on History Grant RM, et al. N Engl J Med. 2010;363:2587-2599. Placebo FTC/TDF 12 10 8 6 4 2 0 Patients Reporting Nausea (%) 96012243648607284 Wks Since Randomization

22. clinicaloptions.com/hiv PrEP and My Patients iPrEx: Weight Gain Placebo FTC/TDF 4 3 2 1 0 Patients Reporting Weight Gain (%) 96012243648607284 Wks Since Randomization Grant RM, et al. N Engl J Med. 2010;363:2587-2599.

23. Adherence

24. clinicaloptions.com/hiv PrEP and My Patients iPrEx: Detected Drug in Infected vs Uninfected Participants HIV infection occurred during periods of low drug exposure Anderson PL, et al. CROI 2012. Abstract 31LB. Drug Detection at Visit with First Evidence of HIV Infection for Case 8% 44% 11% 51% P =.77 100 80 60 40 20 0 09-150-3>21 Pre-HIV Infection Time Points Drug Detection Rate (%) 3-90-33-99-1515-21 >21 Post-HIV Infection Time Points Months 61 145 48 14421 90 207 35 791307136 27 96 31 59 Number of Time Points Case Control 73 P =.001

25. clinicaloptions.com/hiv PrEP and My Patients TDF Levels in PMBC With 2, 4, or 7 Days of DOT: Understanding iPrEX Results 0% 18% Anderson PL, et al. CROI 2012. Abstract 31LB. 100 10 1 % TFV-DP (fmoI/10 6 cells) Detected: Median: IQR: 100 11 6-13 100 32 25-39 100 42 31-47 8 11 4-15 44 16 9-27 iPrEx Visit With First Evidence of HIV STRAND Cases 48 Controls 144 7/wk 22 2/wk 21 4/wk 21 n:

26. Risk Behavior

27. clinicaloptions.com/hiv PrEP and My Patients iPrEx: Numbers of Sexual Partners Grant R, et al. CROI 2011. Abstract 92. Placebo, mean partners FTC/TDF, mean partners 20 15 10 5 0 Sexual Partners in Previous 12 Wks (n) 96012243648607284 Placebo, median partners FTC/TDF, median partners Wks Since Randomization

28. clinicaloptions.com/hiv PrEP and My Patients iPrEx: Condom Use With High-Risk Sex Placebo FTC/TDF 100 80 60 40 0 Receptive Intercourse Using Condoms (% of Partners) 13201260728496108120 Wks Since Randomization 20 243248 Grant R, et al. CROI 2011. Abstract 92.

29. clinicaloptions.com/hiv PrEP and My Patients A Perspective on “Risk Compensation”  Effect of 90% male circumcision ± 30% risk reduction Hallett TB, et al. PLoS One. 2008;3:e2212. No intervention Circumcision intervention only Reductions in risk behavior Reductions in risk behavior + circumcision Intervention Incidence Rate (per 100 Yrs) 2.0 1.5 1.0 0.5 0

30. clinicaloptions.com/hiv PrEP and My Patients Limitations of Current Data  Only ~ 10% of iPrEx population from the US –Arguably, prevention benefit should not differ by geography  Long-term adherence and adherence at time of HIV exposure unknown (in those who became infected)  Long-term health effects of FTC/TDF in HIV negative and HIV seroconverters unknown  Adherence, risk behavior, PrEP interest likely to be different now that results are known compared with clinical trial population CDC. MMWR Morb Mortal Wkly Rep. 2011;60:65-68. Grant RM. N Engl J Med. 2010;363:2587-2599.

31. clinicaloptions.com/hiv PrEP and My Patients What We Are Poised to Learn  PrEP use when MSM know iPrEx results (adherence, risk practices) –iPrEx Open-Label Extension (OLE) –Demonstration projects  What is intermittent dosing and should we consider it? –(Answer: Not yet... )  Efficacy and safety of new drugs and new delivery systems –Long-acting injectables –Rectal microbicides –Vaginal rings

32. clinicaloptions.com/hiv PrEP and My Patients iPrEx [1] InterventionFTC/TDF daily Primary outcomeHIV Population Men 18-67 yrs of age (N = 2499) Risk factorMSM behavior Frequency of outcome in placebo arm 4% per yr Relative risk reduction 44% (95% CI:15% to 63%) How Much Is Enough? A Primary Prevention Comparison 1. Grant RM, et al. N Engl J Med. 2010;363:2587-2599.

33. clinicaloptions.com/hiv PrEP and My Patients iPrEx [1] WOSCOPS [2] InterventionFTC/TDF dailyPravastatin daily Primary outcomeHIVMI Population Men 18-67 yrs of age (N = 2499) Men 45-65 yrs of age (N = 6595) Risk factorMSM behaviorHigh cholesterol Frequency of outcome in placebo arm 4% per yr1.6% per yr Relative risk reduction 44% (95% CI:15% to 63%) 31% (95% CI:17% to 43%) How Much Is Enough? A Primary Prevention Comparison 1. Grant RM, et al. N Engl J Med. 2010;363:2587-2599. 2. Shepherd J, et al. N Engl J Med. 1995;333:1301-1307.

34. Other Studies of ART for Prevention

35. clinicaloptions.com/hiv PrEP and My Patients Partners PrEP: TDF vs TDF/FTC vs Placebo in HIV-Serodiscordant Couples Baeten J, et al. IAS 2011. Abstract MOAX0106. HIV-negative partners in HIV-serodiscordant heterosexual couples (N = 4747) Oral Tenofovir QD (n = 1584) Oral Tenofovir/Emtricitabine QD (n = 1579) Oral Placebo* (n = 1584) *Placebo arm terminated early on July 10, 2011, by data and safety monitoring board. Follow-up: 36 mos

36. clinicaloptions.com/hiv PrEP and My Patients Partners PrEP: Both PrEP Strategies Significantly Reduce HIV Acquisition  Both PrEP strategies associated with significant reduction in HIV acquisition vs placebo in both men and women –TDF efficacy: 71% in women, 63% in men –TDF/FTC efficacy: 66% in women, 84% in men Baeten J, et al. CROI 2012. Abstract 29. Primary Efficacy Outcome, mITT Analysis TDF (n = 1584) TDF/FTC (n = 1579) Placebo (n = 1584) HIV acquisitions, n171352 HIV incidence/100 PY0.650.501.99 Efficacy vs placebo, % (95% CI) 67 (44-81) 75 (55-87) --  P value<.0001 --

37. clinicaloptions.com/hiv PrEP and My Patients Partners PrEP: Other Outcomes  Rates of death, serious adverse events, laboratory events low and not significantly different between arms –Mild GI effects and fatigue, primarily during Month 1  Reported unprotected sexual behavior decreased on study, with similar decline observed across arms  No resistance to TDF or FTC in those who acquired HIV after randomization (n = 27) –Resistance mutations found in 2/8 retrospectively found to have acute HIV-1 at PrEP initiation –K65R (n = 1); M184V (n = 1) Baeten J, et al. CROI 2012. Abstract 29.

38. clinicaloptions.com/hiv PrEP and My Patients TDF2: PrEP With TDF/FTC in HIV-Negative Heterosexuals in Botswana Thigpen MC, et al. IAS 2011. Abstract WELBC01. Oral Tenofovir/Emtricitabine (n = 601) Oral Placebo (n = 599) HIV-uninfected adults, heterosexually active, aged 18-39 yrs (N =1219)* ≥ 12-mo follow-up *n = 19 patients excluded for failure to start study medication or HIV infection.

39. clinicaloptions.com/hiv PrEP and My Patients TDF2: PrEP With TDF/FTC Significantly Reduces HIV Acquisition Thigpen MC, et al. IAS 2011. Abstract WELBC01.  9 vs 24 patients seroconverted in TDF/FTC vs placebo arms, respectively  Overall protective efficacy of TDF/FTC: 62.6% (95% CI: 21.5-83.4; P =.0133)  Reduction in HIV acquisition with TDF/FTC observed in both men and women but study underpowered to demonstrate sex-based differences in outcomes Failure Probability 0.02 0.04 0 0.06 0.08 0123 Yrs TDF/FTC Placebo 0.10 Time to Seroconversion (ITT Analysis)

40. clinicaloptions.com/hiv PrEP and My Patients Disappointing Results of PrEP in Women: FEM-PrEP and VOICE  FEM-PrEP: Phase III study of oral TDF/FTC planned for 3900 high-risk women in Africa (2120 randomized) –Announced April 18, 2011, that study was ended early because of lack of efficacy –35 vs 33 new HIV infections in the placebo and FTC/TDF arms [1] –TFV blood levels that use was too low (< 40%) to assess efficacy –4 vs 1 patient with M184V/I in the TDF/FTC and placebo arms  VOICE: Phase IIB placebo- controlled trial of > 5000 women in South Africa, Uganda, and Zimbabwe [2] –Daily oral TDF; daily oral TDF/FTC; daily vaginal TFV 1% gel –DSMB stopped the daily oral TDF arm in September 2011 and the daily vaginal gel arm in November 2011, both for lack of efficacy –Daily oral TDF/FTC arm continues 1. Van Damme L, et al CROI 2012. Abstract 32LB. 2. These data are available in press release format only, have not been peer reviewed, may be incomplete, and we await presentation or publication in a peer-reviewed format before conclusions should be made from these data.

41. clinicaloptions.com/hiv PrEP and My Patients Questions That Arise From These Data  Why were there differences between these studies and the other TDF-based studies? –Adherence? –Penetration of drug in vaginal tissue? –But promising data on oral PrEP in women in Partners (TDF and TDF/FTC) and TDF2 (TDF) trials –Degree of HIV exposure? –Genital inflammation?

42. clinicaloptions.com/hiv PrEP and My Patients What Have We Learned?  We have proof-of-concept that antiretroviral agents provide primary protection against HIV-1  Adherence to PrEP is critical for its effectiveness –Key component of new PrEP strategies and execution of future PrEP trials  Biomedical prevention is behavioral  We still have much to learn about biologic and behavioral factors that drive HIV-1 risk in women and how those may undermine PrEP benefits

43. Treatment of HIV-Infected Persons for Prevention of Transmission

44. clinicaloptions.com/hiv PrEP and My Patients HPTN 052: Immediate vs Delayed ART for HIV Prevention in Serodiscordant Couples Cohen MS, et al. N Engl J Med. 2011;365: 493-505. Immediate HAART Initiate HAART at CD4+ cell count 350-550 cells/mm 3 (n = 886 couples) Delayed HAART Initiate HAART at CD4+ cell count ≤ 250 cells/mm 3 * (n = 877 couples) HIV-infected, sexually active serodiscordant couples; CD4+ cell count of the infected partner: 350-550 cells/mm 3 (N = 1763 couples) *Based on 2 consecutive values ≤ 250 cells/mm 3.  Primary efficacy endpoint: virologically linked HIV transmission  Primary clinical endpoints: WHO stage 4 events, pulmonary TB, severe bacterial infection and/or death  Couples received intensive counseling on risk reduction and use of condoms

45. clinicaloptions.com/hiv PrEP and My Patients HPTN 052: HIV Transmission Reduced by 96% in Serodiscordant Couples Single transmission in patient in immediate HAART arm believed to have occurred close to time therapy began and prior to suppression of genital tract HIV Total HIV-1 Transmission Events: 39 (4 in immediate arm and 35 in delayed arm; P <.0001) Linked Transmissions: 28 Unlinked or TBD Transmissions: 11 P <.001 Immediate Arm: 1 Delayed Arm: 27 Cohen MS, et al. N Engl J Med. 2011;365: 493-505.

46. clinicaloptions.com/hiv PrEP and My Patients What Do These Results Mean for Others?  Likely that ART prevents transmission in others, although –Only 2 couples from US in HPTN 052 –Other routes of transmission (needles, anal intercourse) and clades (HIV subtypes) may have different transmission biology –No protection for outside partnerships (28% of infections)

47. Why Use PrEP if Treatment Is So Effective?

48. clinicaloptions.com/hiv PrEP and My Patients Challenges in Linkage to Care and Successful Treatment Gardner EM, et al. Clin Infect Dis. 2011;52:793-800. Estimated that only 19% of HIV-infected individuals in the US have undetectable HIV viral load 200,000 600,000 0 800,000 1,000,000 HIV Infected 1,200,000 400,000 HIV Diagnosed Linked to Care Retained in Care Need ART On ART Adherent/Undetectable 1,106,400 874,056 655,542 437,028 349,622 262,217 209,773 19% 24% 32% 40% 59% 79% 100%

49. clinicaloptions.com/hiv PrEP and My Patients What Will It Take to Substantially Reduce HIV Transmission in an Entire Population? Answer: Treatment AND Prevention Gardner EM, et al. Clin Infect Dis. 2011;52:793-800. 200,000 600,000 0 800,000 1,000,000 1,200,000 400,000 19% 22% 34% 28% 21% 66% Number of Individuals CurrentDX 90% Engage 90% Treat 90% VL < 50 in 90% Dx, Engage, Tx, and VL < 50 in 90% Undiagnosed HIV Not linked to care Not retained in care ART not required ART not utilized Viremic on ART Undetectable HIV-1 RNA

50. Concluding Thoughts

51. clinicaloptions.com/hiv PrEP and My Patients “Treatment... costs are unsustainable. Greater emphasis must be placed on preventing new infections.” – Institute of Medicine Report Brief, November 2010 IoM. Preparing for the future of HIV/AIDS in Africa: a shared responsibility. November 29, 2010.

52. Exploring the Practicalities of Providing Antiretroviral Therapy for PrEP

53. The Data and the Need

54. clinicaloptions.com/hiv PrEP and My Patients HIV Diagnoses Among Adult/Adolescent Males by Transmission Group: 2006-2009  40 states and 5 US dependent areas CDC. HIV surveillance in men who have sex with men (MSM). 2011. Male-to-male sexual contact Heterosexual contact* Other † Injection drug use Yr of Diagnosis 2006200720082009 0 5000 10,000 15,000 20,000 25,000 Diagnoses (n) *Heterosexual contact with a person known to have or to be at high risk for HIV infection. † Includes hemophilia, blood transfusion, perinatal exposure, and risk factor not reported or identified. Note: Data include persons with a diagnosis of HIV infection regardless of stage of disease at diagnosis. All displayed data have been statistically adjusted to account for reporting delays and missing risk-factor information but not for incomplete reporting. Male-to-male sexual contact and injection drug use

55. clinicaloptions.com/hiv PrEP and My Patients HIV Diagnoses Among Adult/Adolescent MSM by Age Group: 2006-2009  40 states and 5 US-dependent areas 35-44 25-34 45-54  55 Yr of Diagnosis 2006200720082009 0 1000 3000 4000 6000 7000 Diagnoses (n) 13-24 5000 2000 CDC. HIV surveillance in men who have sex with men (MSM). 2011 Note: Data include persons with a diagnosis of HIV infection regardless of stage of disease at diagnosis. All displayed data have been statistically adjusted to account for reporting delays and missing risk-factor information but not for incomplete reporting.

56. clinicaloptions.com/hiv PrEP and My Patients HIV Diagnoses Among MSM 13-24 Yrs by Race: 2006-2009  40 states and 5 US-dependent areas Hispanic/Latino* 2006200720082009 0 500 1500 2000 3000 3500 2500 1000 American Indian/Alaska Native White Black Multiple races Asian Native Hawaiian/Other Pacific Islander *Hispanics/Latinos can be of any race. Note: Data include persons with a diagnosis of HIV infection regardless of stage of disease at diagnosis. All displayed data have been statistically adjusted to account for reporting delays and missing risk-factor information but not for incomplete reporting. Data exclude men who reported sexual contact with other men and injection drug use. CDC. HIV surveillance in men who have sex with men (MSM). 2011. Diagnoses (n) Yr of Diagnosis

57. Are We Ready to Give PrEP to Men in the United States?

58. clinicaloptions.com/hiv PrEP and My Patients  Note: This is interim guidance  CDC and other USPHS agencies are developing formal guidelines for the use of PrEP in MSM in the US  Additional guidance for other populations will become available as data from newer studies are more fully analyzed CDC. MMWR Morb Mortal Wkly Rep. 2011;60:65-68.

59. clinicaloptions.com/hiv PrEP and My Patients Goals of CDC Interim PrEP Guidance  CDC interim guidance reinforced: –TDF/FTC is the only proven effective PrEP regimen for MSM –Daily dosing of PrEP is the only proven effective regimen –Intermittent use efficacy unknown –PrEP efficacy was demonstrated with HIV testing and other prevention services –Until analyses complete from other PrEP trials, PrEP recommended only for MSM populations CDC. MMWR Morb Mortal Wkly Rep. 2011;60:65-68.

60. Before Initiating PrEP: Risk Assessment

61. clinicaloptions.com/hiv PrEP and My Patients Before Initiating PrEP: Risk Assessment  Guidance applies only to MSM  Components of CDC behavioral risk assessment –Risk-reduction measures (eg, condoms) not used or used consistently –Risk for HIV acquisition is high –Frequent partner changes –Partners with HIV-positive or unknown HIV status –Geographic setting with high HIV prevalence CDC. MMWR Morb Mortal Wkly Rep. 2011;60:65-68.

62. clinicaloptions.com/hiv PrEP and My Patients Will Men Be Interested in PrEP?  After yrs of telling men not to get HIV because the medications are awful  Messaging about safety and tolerability of FTC/ TDF is important  Helping men decide whether they would likely benefit from PrEP is essential

63. clinicaloptions.com/hiv PrEP and My Patients CDC: PrEP Eligibility  HIV uninfected –Antibody negative, immediately before starting PrEP –If patient has symptoms consistent with acute HIV infection, either wait for 1 mo and confirm HIV negative and/or test for acute HIV infection  Adequate renal function –Creatinine clearance ≥ 60 mL/min (Cockcroft-Gault)  Additional recommended actions –Screen for hepatitis B infection –If HBV uninfected and susceptible → vaccine (MSM in US should be vaccinated against HBV) –If HBV infected, treat for HBV (potentially with FTC/TDF) –Screen and treat STDs CDC. MMWR Morb Mortal Wkly Rep. 2011;60:65-68.

64. clinicaloptions.com/hiv PrEP and My Patients Prescribing PrEP  Coformulated FTC 200 mg/TDF 300 mg, 1 tablet daily  No more than 90-day supply  Renewable only if HIV testing confirms the patient remains HIV uninfected –Anticipate, at minimum, quarterly HIV testing CDC. MMWR Morb Mortal Wkly Rep. 2011;60:65-68. Grant RM, et al. N Engl J Med. 2010;363:2587-2599.

65. clinicaloptions.com/hiv PrEP and My Patients Counseling  Continued behavioral risk reduction  Importance of PrEP adherence –No data on intermittent, “event-driven” use  Adverse events –Very well tolerated and safe –May experience mild nausea in first few wks

66. clinicaloptions.com/hiv PrEP and My Patients Follow-up  HIV testing –Every 2-3 mos; document negative result  Evaluate and support adherence  Continued risk-reduction counseling –Assess for STD symptoms at each visit –Screen asymptomatic patients every 6 mos  Renal safety –Test creatinine after 3 mos on PrEP and annually thereafter CDC. MMWR Morb Mortal Wkly Rep. 2011;60:65-68.

67. clinicaloptions.com/hiv PrEP and My Patients Discontinuing PrEP  HIV testing –If HIV positive, stop PrEP –Resistance testing –Establish linkage to HIV care –If HIV negative, risk-reduction support services  If person has chronic hepatitis B infection –Check liver function tests (case reports of hepatitis flares after discontinuing FTC/TDF) CDC. MMWR Morb Mortal Wkly Rep. 2011;60:65-68.

68. clinicaloptions.com/hiv PrEP and My Patients PrEP Safety  PrEP with FTC/TDF or any other medication currently has no label indication –FDA currently considering application for an indication for FTC/TDF for PrEP  Serious adverse events –Should be reported to the FDA’s MedWatch (www.fda.gov/safety/medwatch) CDC. MMWR Morb Mortal Wkly Rep. 2011;60:65-68.

69. clinicaloptions.com/hiv PrEP and My Patients PrEP Reimbursement  Public or private insurance may or may not cover the costs associated with PrEP –ADAP funds cannot be used to pay for PrEP  Options being investigated –Likely to be influenced by FDA decision and/or CDC recommendations

70. clinicaloptions.com/hiv PrEP and My Patients Unknowns  Populations in which PrEP can be used effectively and safely –Long-term toxicity in HIV-negative person unknown  Adherence –Long term –Intermittent use  Resistance –Longer time between HIV tests –Persistence and spread of resistant virus, if occurs  Behavior –How much will behavior change if PrEP is partially protective? –How much will that impact efficacy?

71. clinicaloptions.com/hiv PrEP and My Patients Summary: Prescribing PrEP  Daily FTC/TDF shown to have moderate efficacy for HIV-1 prevention among MSM –High efficacy among those with high adherence –PrEP is a promising HIV prevention strategy for MSM  Daily TDF and FTC/TDF safe and efficacious among heterosexual couples and young heterosexuals in Partners PrEP and TDF2 –Mixed results from other trials; more interpretation necessary  Additional data forthcoming on oral FTC/TDF in women, and TDF in IDUs  CDC and WHO guidelines forthcoming  Providers should be prepared to do risk assessment, counseling, and prescribe for high-risk MSM  Risk assessment and counseling tools to aid providers and prospective users are under development

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