Ending the Epidemic: What Clinicians Need to Know

Ending the Epidemic: What Clinicians Need to Know Mary Goodspeed, RN, BS Coordinator, HIV Clinical Education Erie County Medical Center 716-898-4713 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 1

In July 2014, Governor Andrew Cuomo announced a 3-point plan to end the AIDS epidemic in NYS by the year 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. Strategies to End the Epidemic include: A. Make routine HIV testing truly routine B. Link and retain all positive patients to care C. Treat early to maximize HIV virus suppression so patients remain healthy and to prevent further transmission D. Increase use of npost Exposure Prophylaxis (npep) and Pre Exposure Prophylaxis (PrEP) E. 2 & 3 F. All of the above 0% 3% Increase use of npost E... Make routine HIV testing... Link and retain all positi.. Treat early to maximize... 0% 94% 0% 3% 2 & 3 All of the above 4 2

The NYS End the Epidemic Initiative plans on decreasing new HIV infections by 2020 from 3,000 a year to A. 1,500 B. 1,000 C. 750 D. 0 38% 48% 13% 3% 1,500 1,000 750 0 5 Ending the Epidemic (ETE) 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 3

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 NYS HIV Testing Law 1. Providers legally mandated to offer HIV testing to all persons ages 13 64. 2. Prior to asking for consent to perform HIV test, providers must make seven points of information about HIV available to patients 3. Consent for HIV testing can be verbal 4. Test providers are legally required to arrange an appointment for follow-up HIV care to all persons who test positive for HIV 5. HIV information may be released to medical providers & health insurers without a written disclosure statement from patient 6. Deceased, comatose, or persons incapable of providing consent who are the source of an occupational exposure may now be HIV tested anonymously 4

Public Health Law Amended Key Provisions of the legislation include: Elimination of the requirement for written consent prior to ordering an HIV-related test in any circumstance including correctional facilities, local prisons or jails (Public Health Law 2781 2-a) Oral notification to be provided to the individual being tested, if individual lacks capacity, to the person lawfully authorized to consent for healthcare of the individual The individual must be told each time an HIV test will be done and given the opportunity to decline. All tests must be documented in the patients medical record Information about HIV testing will be provided via posters, brochures, videos or by providers to the patient with the opportunity to accept or refuse testing Required Offer Who/Where? Physicians, Nurse Practitioners, Nurse Midwives and Physician Assistants In these health care settings: Inpatient department of hospitals Emergency departments Primary care services in outpatient departments of hospitals Primary care services in diagnostic and treatment centers (includes school-based clinics & family planning sites) 5

How Soon After Exposure to HIV Can Tests Detect the Virus? Even among antibody tests, the window period varies The so-called first-generation and second-generation HIV antibody tests detect one type of HIV antibody, 42-60 days after infection Third-generation tests detect all types of antibodies, making them more sensitive than the first and second-generation tests, about 21-24 days after infection Fourth-generation tests can simultaneously detect both HIV antibodies and antigens. Tests that look for the p24 antigen can detect it within 14-15 days. Tests can detect plasma HIV RNA (ribonucleic acid) within about 10 days of infection It is important to know the HIV test(s) your agency or lab uses so you can provide patients with the best advice. Blueprint April 2015 6

New HIV Infections Do Not Happen in Isolation, but Come Tied to Numerous Factors 1) Poor Health Care Lack of access to medications, condoms, syringes No medical insurance, lack of competent medical providers Lack of health support, peer navigators, adherence support No easy access to HIV/STD screening and treatment Lack of health and sexual education Delay from testing to linkage 2) Poverty, which includes: lack of housing food insufficiency unemployment/underemployment survival sex work and inequality: o incarceration o undocumented status o stigmatization o unfair drug laws o disempowerment o domestic violence o bullying o penalization of condom carriers 7

3)Mental health problems, such as: substance abuse depression impulsivity fatalism disengagement religious guilt cognitive problems history of traumatic experiences 4)Geographic Disadvantage: transportation issues engaging in high risk behavior in areas with high HIV prevalence Self Perception of HIV Risk is Low Persons (N=3,533; >90% African-American) undergoing HIV rapid testing in Philadelphia were surveyed between July 2012 and Dec 2013 9.5% SELF Perception Perception as moderate/high Risk TESTERS Perception Perception as moderate/high risk 68.5% A large proportion of patients at high-risk for HIV infection do not perceive themselves at high risk Kwakwa H, et al. IAC 2014; Melbourne, Australia. #TUPE090 8

Blueprint Recommendations 1) Identify HIV+ Undiagnosed Make routine HIV testing truly routine Expand targeted testing Address acute HIV infection Improve referral and engagement Blueprint Recommendations 2) Link, Retain and Support Viral Suppression Continuously act to monitor and improve rates of viral suppression Incentivize performance Use client-level data to identify and assist patients lost to care or not virally suppressed Enhance and streamline services to support the non-medical needs of all persons with HIV Provide enhanced services for patients within correctional and other institutions specific programs for patients returning from corrections Maximize opportunities through the Delivery System Reform Incentive Payment (DSRIP) process to support programs to achieve goals related to L, R, T & A 9

Blueprint Recommendations 3) PrEP and Medical Providers Undertake a statewide education campaign on PrEP and npep Include a variety of statewide programs for distribution and increased access to PrEP and npep Create a coordinated statewide mechanism for persons to access PrEP and npep prevention focused care Develop mechanisms to determine PrEP and npep usage and adherence statewide Pre-Exposure Prophylaxis, PrEP, is recommended for at risk negative individuals to prevent HIV transmission, they would include: A. Serodiscordant couples B. Men who have sex with men who engage in unprotected anal sex C. Individuals who engage in transactional sex D. Injection drug users who share needles E. 1,2 & 4 F. All of the above Serodiscordant couples 2% 0% Men who have sex with... Individuals who engage i... 0% Injection drug users who... 0% 2% 1,2 & 4 All of the above 95% 20 10

PrEP 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 11

iprex Trial Phase 3, double-blind, randomized, placebocontrolled, 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. Pre-exposure 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 12

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 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 lifethreatening (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 13

probability 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 HPTN 052: Treatment as Prevention in HIV+ Persons 1,763 discordant couples (97% heterosexual) in Africa, Asia, Americas. Those HIV+ had CD4 range of 350-550 HIV+ partner randomized to start HIV treatment immediately or deferred until CD4 <250 DSMB Interim analysis: 90% on ART had HIV RNA <400 40 incident cases of HIV 29 linked genetically to partner 96% reduction in transmission! New HIV infections (all) 28 cases years 1 case Cohen IAS 2011 #MOAX0102 and NEJM 2011;365:493 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 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 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-forthe-use-of-pre-exposure-prophylaxis-prep-to-prevent-hiv-transmission/ 15

Common Examples of Pre-Exposure Prophylaxis A woman taking birth control pills to prevent pregnancy A traveler taking anti-malaria medications when going to an area where there is high likelihood of exposure to malaria A person taking antibiotics prior to dental surgery to prevent infection A person with HIV taking certain medications to prevent an opportunistic infection Potential Candidates for PrEP Men who have sex with men (MSM) who engage in unprotected anal intercourse 7,8 Individuals who are in a serodiscordant sexual relationship with a known HIVinfected partner Male-to-female and female-to male transgender individuals engaging in highrisk sexual behaviors Individuals engaging in transactional sex, such as sex for money, drugs, or housing Injection drug users who report any of the following behaviors: sharing injection equipment (including to inject hormones among transgender individuals), injecting one or more times per day, injecting cocaine or methamphetamine, engaging in high-risk sexual behaviors 6 Individuals who use stimulant drugs associated with high-risk behaviors, such as methamphetamine 7-10 Individuals diagnosed with at least one anogenital sexually transmitted infection in the last year 11,12 Individuals who have been prescribed non-occupational post-exposure prophylaxis (npep) who demonstrate continued high-risk behavior or have used multiple courses of npep 13 16

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 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-forthe-use-of-pre-exposure-prophylaxis-prep-to-prevent-hiv-transmission/ http://www.hivguidelines.org/clinical-guidelines/pre-exposure-prophylaxis/guidance-for-theuse-of-pre-exposure-prophylaxis-prep-to-prevent-hiv-transmission/ 17

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 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/guidancefor-the-use-of-pre-exposure-prophylaxis-prep-to-prevent-hiv-transmission/ http://www.hivguidelines.org/clinical-guidelines/pre-exposure-prophylaxis/guidance-for-theuse-of-pre-exposure-prophylaxis-prep-to-prevent-hiv-transmission/ 18

Key Components of PrEP Deliver PrEP as part of a comprehensive set of prevention services ( bundle ) Risk reduction Access to condoms Identification and treatment of STIs Taking one pill (Truvada) once every day Medication adherence counseling Medical Appointments for PrEP Initial Appointment: HIV testing; PrEP is provided for only 30 days One Month Follow-Up: Provider assesses person s experience on PrEP including adherence, side effects and commitment. At this visit a prescription for 60 days may be given; Three Month Follow-Up: HIV testing and other assessments; prescription for 90 days if HIV negative and adherent; Every Three Months: HIV testing and other assessments repeated every three months; prescription for 90 days if HIV negative and adherent. 19

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 Patient Education Educate about the following: How PrEP works Limitations of PrEP PrEP Use Common side effects 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, anti-gas, 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. 20

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-forthe-use-of-pre-exposure-prophylaxis-prep-to-prevent-hiv-transmission/ 21

Can TRUVADA for PrEP Be Used During Pregnancy? There are no adequate and well-controlled studies of TRUVADA for PrEP in pregnant women Use TRUVADA for PrEP during pregnancy only if clearly needed In uninfected women who become pregnant while taking TRUVADA for PrEP, careful consideration about continuing TRUVADA should be given, taking into account the potential increased risk of HIV-1 infection during pregnancy To monitor fetal outcomes of pregnant women exposed to antiretroviral regimens, an Antiretroviral Pregnancy Registry (APR) has been established. Health care providers are encouraged to register patients by calling 800-258-4263 http://www.apregistry.com/. The Overlooked Secondary Benefits of PrEP Frank discussions about sex and risk If We Don t Ask, Patients Won t Tell Increased attention to screening, prevention and treatment of STDs New attention to fighting stigma Discussions about pregnancy in discordant couples Encouraging people to seek primary care 44 22

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? NYSDOH PrEP Provider list http://www.hivguidelines.org/clinical-guidelines/pre-exposure-prophylaxis/guidance-for-the-useof-pre-exposure-prophylaxis-prep-to-prevent-hiv-transmission/ Financial Implications for PrEP Costs: Drug: $1425/month = $17,000 yearly Lab monitoring: $374-$504 yearly Professional Fees: $310 yearly CDC - Lifetime Cost of treating HIV - $379,000 (In 2010 dollars) Horberg. AMJ Prev Med 44 (1) : S125 23

Concluding Thoughts Treatment... costs are unsustainable. Greater emphasis must be placed on preventing new infections. Institute of Medicine Report Brief, November 2010 47 A word about stigma 24

Strategies to End the Epidemic include: A. Make routine HIV testing truly routine B. Link and retain all positive patients to care C. Treat early to maximize HIV virus suppression so patients remain healthy and to prevent further transmission D. Increase use of npost Exposure Prophylaxis (npep) and Pre Exposure Prophylaxis (PrEP) E. 2 & 3 F. All of the above Make routine HIV testing... Link and retain all positi.. 0% 0% 0% Treat early to maximize... Increase use of npost E... 100% 0% 0% 2 & 3 All of the above 49 Strategies to End the Epidemic include: Make routin... 100 100 Link and re... 100 100 Treat early... 100 100 Increase us... 100 100 2 & 3 100 100 All of the... 100 100 First Slide Second Slide 25

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. 26