Pre-Exposure Prophylaxis (PrEP) and the Governor s Plan to End AIDS: What Every Clinician Needs to Know ANTONIO E. URBINA, MD Medical Director Associate Professor of Medicine Mt. Sinai Hospital
Disclosure Advisory Panel: Merck, Theratechnologies
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LEARNING OBJECTIVES: 1. List the three points of the Governor s Plan to End AIDS 2. Describe clinical trial data that contributes to the scientific understanding of PrEP as a safe and effective biomedical prevention strategy 3. Discuss potential candidates for PrEP and the importance of referral to a clinician experienced in managing PrEP 4. Describe the impact of stigma on a patient s decision to start and adhere to PrEP
In July 2014, Governor Andrew Cuomo announced a 3-point plan to end the AIDS epidemic in NYS by the year 2020.
Three-Point Plan Identify HIV+ undiagnosed Link, retain, support viral suppression PrEP for high-risk persons Identify persons with HIV who remain undiagnosed and link them to health care Link and retain persons diagnosed with HIV to health care and start them on anti- HIV therapy to maximize HIV virus suppression to remain healthy and prevent further transmission Provide access to preexposure prophylaxis (PrEP) for high-risk persons to keep them HIV negative
What does it mean to End the AIDS Epidemic? The end of the AIDS epidemic in New York will occur when the total number of new HIV infections has fallen below the number of HIVrelated deaths. The goal is to reduce the number of new HIV infections to just 750 by 2020.
Bending the Curve By the end of 2020 Reduce new HIV infections from 3,000 to 750 Reduce the rate at which persons diagnosed with HIV progress to AIDS by 50% 2015 Blueprint
Ending the Epidemic by 2020 "Thirty years ago, New York was the epicenter of the AIDS crisis -- today I am proud to announce that we are in a position to be the first state in the nation committed to ending this epidemic. Governor Andrew M. Cuomo
Blueprint April 2015
Blueprint: PrEP and Medical Providers BP11: Undertake a statewide education campaign on PrEP and npep BP12: Include a variety of statewide programs for distribution and increased access to PrEP and npep
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;363:2587-2599. 2. Baeten JM, et al. Antiretroviral prophylaxis for HIV prevention in heterosexual men and women. N Engl J Med 2012;367:399-410. 3. Thigpen MC, et al. Antiretroviral preexposure prophylaxis for heterosexual HIV transmission in Botswana. N Engl J Med 2012;367:423-434. 4. Van Damme L,et al. Preexposure prophylaxis for HIV infection among African women. N Engl J Med 2012;367:411-422. 5. 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, 2013. 6. 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;381:2083-2090.
iprex Trial
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
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
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
iprex Results 44% reduction, P=0.002 95% 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
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
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
iprex: HIV by Group and Drug Detection Group Drug Detection HIV Infections Incidence Density Placebo No 64 3.86 FTC/TDF No 33 4.04 Yes 3 0.35 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
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 86% 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% Kahle E, et al. 19th IAC; Washington, DC; July 22-27, 2012; Abst. TUAC0102. NR
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 http://www.cdc.gov/hiv/prevention/research/prep/
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 http://www.cdc.gov/hiv/pdf/prepguidelines2014.pdf http://www.cdc.gov/hiv/pdf/prepprovidersupplement2014.pdf
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 http://www.cdc.gov/hiv/prevention/research/prep/
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 http://www.cdc.gov/hiv/prevention/research/prep/
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 www.hivguidelines.org http://www.hivguidelines.org/clinical-guidelines/pre-exposure-prophylaxis/guidance-for-theuse-of-pre-exposure-prophylaxis-prep-to-prevent-hiv-transmission/
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 http://www.hivguidelines.org/clinical-guidelines/pre-exposure-prophylaxis/guidance-forthe-use-of-pre-exposure-prophylaxis-prep-to-prevent-hiv-transmission/
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 http://www.hivguidelines.org/clinical-guidelines/pre-exposure-prophylaxis/guidance-for-theuse-of-pre-exposure-prophylaxis-prep-to-prevent-hiv-transmission/
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;60:421-427. 2. 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;10:2285-2294 3. 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;34:689-694 5. Menza TW, et al. Prediction of HIV acquisition among men who have sex with men. Sex Transm Dis 2009;36:547-555. 6. Heuker J, et al. High HIV incidence among MSM prescribed postexposure prophylaxis, 2000-2009: Indications for ongoing sexual risk behaviour. AIDS 2012;26:505-512
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;60:421-427.
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 http://www.hivguidelines.org/clinical-guidelines/pre-exposure-prophylaxis/guidance-forthe-use-of-pre-exposure-prophylaxis-prep-to-prevent-hiv-transmission/
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 http://www.hivguidelines.org/clinical-guidelines/pre-exposure-prophylaxis/guidance-for-the-useof-pre-exposure-prophylaxis-prep-to-prevent-hiv-transmission/
Educate about the following: How PrEP works Limitations of PrEP PrEP Use Common side effects NYS DOH Guidance Patient Education Talking Points: 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;4:151ra125. 2. 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:e55013. 3. 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.
NYS DOH Guidance 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.
PrEP 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. http://www.hivguidelines.org/clinical-guidelines/pre-exposure-prophylaxis/guidance-for-theuse-of-pre-exposure-prophylaxis-prep-to-prevent-hiv-transmission/
Linkage to PrEP Knowledge about PrEP Patient understanding and misconceptions Health Literacy Readiness and willingness to adhere to PrEP Primary Care Does the patient have a PCP? Referral to PrEP at Albany Medical Center? http://www.hivguidelines.org/clinical-guidelines/pre-exposure-prophylaxis/guidance-for-the-useof-pre-exposure-prophylaxis-prep-to-prevent-hiv-transmission/
A word about stigma
Summary PrEP is now part of a menu of evidence-based interventions to prevent HIV transmission. PrEP may be an effective option to augment behavior change. It is important to identify at-risk individuals for referral and linkage to PrEP services. Stigma can play a large role in patient and provider barriers to accessing PrEP.
Thanks! Naomi Harris Charles King Terri Wilder 40
Questions? Antonio E. Urbina, MD aurbina@chpnet.org Clinical questions regarding PrEP? Please phone the CEI Line at 1-866-637-2342 or visit www.ceitraining.org