Why, When, and How to Use Pre-Exposure Prophylaxis (PrEP) for HIV Acquisition: Guidance for Midlevel Practitioners Marcy S. Gelman, RN, MSN, MPH Director.

Why, When, and How to Use Pre-Exposure Prophylaxis (PrEP) for HIV Acquisition: Guidance for Midlevel Practitioners Marcy S. Gelman, RN, MSN, MPH Director of Operations and Clinical Research The Fenway Institute Fenway Community Health Boston, Massachusetts Kevin M. O’Hara, PA Assistant Professor of Medicine Physician Associate Program Yale School of Medicine New Haven, Connecticut Thank you for joining us for this important training for midlevel practitioners, “Why, When, and How to Use Pre-Exposure Prophylaxis (PrEP) for HIV Acquisition: A Guidance for Midlevel Practitioners.” This activity is supported by an independent educational grant from Gilead Sciences.

About These Slides 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 Users are asked to honor this intent These slides may not be published or posted online without permission from Clinical Care Options ( Disclaimer The materials published on the Clinical Care Options Web site reflect the views of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.

Faculty Marcy S. Gelman, RN, MSN, MPH Director of Operations and Clinical Research The Fenway Institute Fenway Community Health Boston, Massachusetts Kevin M. O’Hara, PA Assistant Professor of Medicine Physician Associate Program Yale School of Medicine New Haven, Connecticut My name is Kevin O’Hara. It’s a pleasure to be working with you. And I’m Marcy Gelman, Adult Nurse Practitioner in Boston, Massachusetts.

Faculty Disclosures Marcy S. Gelman, RN, MSN, MPH, has no significant financial relationships to disclose. Kevin M. O’Hara, PA, has disclosed that he has ownership interest in AbbVie and Gilead Sciences.

Introduction to the Use of PrEP in Clinical Practice
PrEP, pre-exposure prophylaxis. Introduction to the use of PrEP in clinical practice.

HIV/AIDS in the United States and Worldwide
Approximately 1.1 million people are living with HIV/AIDS in the United States An estimated 1 in 6 (15.8%) of those people are undiagnosed Since the start of the epidemic, 636,000 people have died of AIDS An estimated 50,000 new HIV infections occur in the US every yr More than 35 million people are living with HIV/AIDS worldwide, of whom 3.3 million are younger than 15 yrs of age In 2012, an estimated 2.3 million people were newly infected with HIV HIV in the US and worldwide continues to be a major public health crisis. There is an estimated 1.1 million Americans living with HIV, and 1 out of 6 people with HIV do not know they are infected. HIV continues to spread, leading to about 50,000 new cases of HIV each year in the US alone. An increase in the number of individuals living with HIV reflects the success of antiviral therapy, which has turned HIV from a fatal condition into a chronic illness. However, it also means that there are more people capable of transmitting the infection to others. CDC. HIV Surveillance Report. 2013;18(no.5). CDC. HIV Surveillance Report, 2011; vol. 23. UNAIDS Report On the Global AIDS Epidemic 2013.

The Need for HIV Prevention: Continued HIV Risk in the US
Estimated new HIV infections in the United States for the most affected subpopulations, 70 60 Male-to-male sexual contact Heterosexual contact IDU Male-to-male sexual contact and IDU Other 50 40 Diagnoses (%) 30 IDU, injection drug user. It’s important to consider who is at most risk for acquiring HIV. Gay, bisexual, and other men who have sex with men make up 64% of all HIV-infected people in the United States. Black and African-American men who have sex with men are at increased risk of acquiring and transmitting HIV. Whereas heterosexual men and women and persons who inject drugs have been decreasing, the number among MSM continue to rise. As providers, we must be aware of our own risk communities when we talk about prevention and prevention methods. 20 10 2008 2009 2010 2011 Yr CDC. HIV in the United States: 2013.

HIV Prevention: Toolbox for Success
Safer-sex counseling: understanding risk Condoms and lubricant Sterile syringes and avoiding sharing “works” HIV testing STI testing and treatment PEP (postexposure prophylaxis) PrEP (pre-exposure prophylaxis) PEP, postexposure prophylaxis; PrEP, pre-exposure prophylaxis; STI, sexually transmitted infection. As providers we must understand the HIV prevention methods available and support our patients to understand and use the methods that best suit their lifestyles. Safer-sex counseling from healthcare providers or HIV testing counselors is critical for understanding sexual practice and risk associated negotiation and safety. Using condoms with water-based lubricant continues to remain critical and a vital tool for ongoing safety, not only for the prevention of HIV but also for other sexually transmitted infections. Getting tested for HIV is one of the most important factors in community HIV prevention. And getting testing and treated for STIs is critical, as having an STI can increase your chance of becoming infected with HIV, and it is also an indicator for providers and patients of risk. In addition, we must provide sterile and clean needles for injecting drug users and safe places to access and dispose of needles. Finally, we have several biomedical methods of prevention.

What Is PrEP? For PrEP, an HIV-uninfected individual takes antiretroviral medication(s) before potential HIV exposure The idea of providing a medication as prophylaxis against an infectious disease is well established, eg: Use of antimalarials before traveling to malarial zones Use of antibiotics prior to dental procedures Oral contraceptives are also used prophylactically to prevent pregnancy PrEP, pre-exposure prophylaxis. Pre-exposure prophylaxis, or PrEP, is a strategy that involves use of antiretroviral medications to reduce the risk of HIV infection. The idea of using a well-tolerated and highly effective method of prevention has been well understood in medicine; consider prevention of malaria and antibiotics before dental procedures. Today, PrEP is a pill taken once a day, which we will continue to talk more about in this discussion.

Antiretrovirals Used in HIV Prevention: The Foundation for PrEP
Prevention of mother-to-child transmission Antiretrovirals given to the mother during pregnancy, labor, and delivery and to the infant postpartum[1] PMTCT has virtually eliminated perinatal HIV infection in the US and other developed countries Postexposure prophylaxis Antiretrovirals given within hrs of a known or suspected HIV exposure (eg, needle stick injury, rape) US public health guidance for PEP is available for both occupational[2] and nonoccupational[3] exposure to HIV PEP, postexposure prophylaxis; PMTCT, prevention of mother-to-child transmission; PrEP, pre-exposure prophylaxis. To further enhance the argument that antivirals could be highly effective in the prevention of HIV for those at risk is the success of using antivirals in prevention of mother-to-child transmission, which has essentially eradicated new infections at birth in the United States. In addition, PEP, or postexposure prophylaxis, has been used for many years in both occupational and nonoccupational exposures. DHHS. Perinatal Guidelines Kuhar DT, et al. Infect Control Hosp Epidemiol. 2013;34: 3. MMWR. 2005;54(RR-2):1-20.

Pre- vs Postexposure Prophylaxis
After exposure to HIV, infection may become established Postexposure prophylaxis (initiated soon after exposure) reduces the chance of infection Pre-exposure prophylaxis begins treatment earlier (before exposure), which might increase the prophylactic effect HIV infection HIV exposure Postexposure prophylaxis Understanding the difference between pre- and postexposure prophylaxis and educating our patients is critical for uptake and timely prevention of HIV. For a person who has one or very infrequent exposures to HIV, they could begin the use of PEP, or postexposure prophylaxis, by 72 hours of that exposure, and then take antivirals for 28 days, with the goal of preventing HIV from replicating. For people who have repeated known exposures to HIV or engage in high-risk activity, the possibility of taking a pill prior to those exposures and continuing that throughout the course of exposure may be more effective than them taking a pill after an exposure. This is PrEP, or pre-exposure prophylaxis. Pre-exposure prophylaxis 0 hr 36 hrs 72 hrs 1 mos 3 mos 5 mos

Reduction in HIV Infection Rate, % (95% CI)
PrEP Trials Have Shown Efficacy in MSM, Heterosexual Men and Women, and IDUs Trial Population/Setting Intervention HIV Infections, n Reduction in HIV Infection Rate, % (95% CI) PrEP Placebo iPrEX[1] (N = 2499) MSM, transgender women, 11 sites in US, South America, Africa, Thailand TDF/FTC 36 64 44 (15-63) Partners PrEP[2] (N = 4747) Serodiscordant couples in Africa TDF 17 52 67 (44-81) 13 75 (55-87) TDF2[3] (N = 1219) Heterosexual males and females in Botswana 9 24 62 (21-83) Thai IDU[4] (N = 2413) Volunteers from 17 drug Thai treatment centers 33 49 (10-72) FTC, emtricitabine; IDU, injection drug user; MSM, men who have sex with men; PrEP, pre-exposure prophylaxis; TDF, tenofovir. The past few years, there have been major breakthroughs in biomedical research for HIV prevention. We now have data from large clinical trials to support the hypothesis that pre-exposure prophylaxis can prevent HIV. Four large clinical trials around the globe have used tenofovir or tenofovir/FTC in MSM, serodiscordant couples, heterosexual men and women, and persons who use injection drugs. All of these trials have shown reduction in HIV incidence, with higher percent reduction in those who were taking the active study pill as opposed to the placebo. The results of the iPrEx study resulted in the FDA approval in July 2012 of tenofovir/FTC, the first drug to be approved for HIV prevention. 2 additional trials of PrEP (FEM-PrEP[5] and VOICE[6]), both conducted among high-risk African women, did not demonstrate protection against HIV; in both trials, PrEP adherence was very low 1. Grant RM, et al. N Engl J Med. 2010;363: Baeten JM, et al. N Engl J Med. 2012;367: Thigpen MC, et al. N Engl J Med. 2012;367: Choopanya K, et al. Lancet. 2013;381: Van Damme L, et al. N Engl J Med. 2012;367: Marrazzo J, et al. CROI Abstract 26LB.

PrEP Works, but Adherence Is Critical
Study Efficacy Overall, % Blood Samples With TFV Detected, % Efficacy By Blood Detection of TFV, % iPrEx[1] 44 51 92 iPrEx OLE[2] 49 71 NR Partners PrEP[3] 67 (TDF) 75 (TDF/FTC) 81 86 (TDF) 90 (TDF/FTC) TDF2[4] 62 80 85 Thai IDU[5] 67 74 Fem-PrEP[6] No efficacy < 30 VOICE[7] FTC, emtricitabine; NR, not reported; PrEP, pre-exposure prophylaxis; TDF, tenofovir disoproxil fumarate; TFV, tenofovir. Oral PrEP works, but adherence is critical. For IPrEx, when you analyze efficacy with the detection of tenofovir in the person’s blood, it showed that if you took tenofovir as instructed, the efficacy of PrEP was 92%. 1. Grant RM, et al. N Engl J Med. 2010;363: Grant RM, et al. Lancet Infect Dis. 2014; 14: Baeten JM, et al. N Engl J Med. 2012;367: Thigpen MC, et al. N Engl J Med. 2012;367: Choopanya K, et al. Lancet. 2013;381: Van Damme L, et al. N Engl J Med. 2012;367: Marrazzo J, et al. CROI Abstract 26LB.

PrEP in Clinical Practice: What Are the Barriers to PrEP Uptake?
Users 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 Providers 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 PrEP, pre-exposure prophylaxis. I’ve spent the last few years doing a lot of work on PrEP, in a private practice setting. I have seen a lot of people who have read a newspaper and journal articles who have come to me for PrEP. I find many times I don’t even have to bring it up. So patient awareness has been not so much an issue for me. What have you seen? We have noticed that patient awareness seems to be a problem. In Boston, we’re finding that the uptake is much lower than we thought it would be. In addition, what has been interesting is the lack of awareness among providers—primary care providers, various midlevel practitioners, and HIV specialists. There has also been the situation in which primary care providers do not feel comfortable prescribing antiretrovirals, and HIV providers don’t work with HIV-uninfected individuals. So there’s been this discussion about where does PrEP best lie. In addition, I think that seeing patients every 3 months has also been a barrier for providers and for patients who are essentially healthy and want to prevent HIV. In discussing these barriers as research researchers and clinicians, we’ve really been surprised at the slow uptake of PrEP, and it’s made us think and talk about the various barriers that we might be facing for both the users and for the providers. Potential users may not be aware of their own risk, which is really critical, or the availability of PrEP. They may not know how to access PrEP or access preventative care. They may not be able to identify a well-informed provider who understands and is willing to write a prescription. They also may not have the means to obtain or pay for these prescriptions, and they may have challenges with proper daily use as is prescribed today. For providers, they may also not be aware of the intervention, how to bill for these visits, or they may be concerned about the complexity of the visit and the time it takes to see these patients. In addition and one of the barriers that we see frequently is providers and patients may be uncomfortable talking about the risks.

Risk Assessment and Shared Decision Making
This brings us to the next part of our presentation where we discuss risk assessment and shared decision making.

Provider–Patient Decision Making
The role of the provider is to help the patient: Understand the likely outcomes of various options Think about what is personally important about the risks and benefits of each option Participate in decisions These decisions are difficult because: There may be more than 1 choice Each choice has advantages and disadvantages There is no “correct” choice; what you choose depends on what is important to you In order to support our patients to make the best decision for themselves, we as providers should engage and share decision making with them. This is a collaborative process that allows patients and providers to make healthcare decisions together, take into account the best scientific evidence available, as well as the patient’s values and preferences. It’s especially useful when there is no clear best treatment option, and this is true in the case of HIV prevention. When thinking about HIV prevention, it’s important to get to know your patients, what they would like to consider to use in their toolbox to prevent HIV. In some cases, patients will have no idea that they might be at risk, or they may be misguided by myths and lack of information. As providers, it is our job to educate, inform, and lay out the options for them so that they can best protect themselves from HIV.

CDC PrEP Guideline: For Which Patients Is PrEP Recommended?
PrEP is recommended as one prevention option for the following adults at substantial risk of HIV acquisition Sexually active MSM Heterosexually active men and women Injection drug users MSM Heterosexual Women and Men Injection Drug Users Potential indicators of substantial risk of acquiring HIV infection HIV-positive sexual partner Recent bacterial STI High number of sex partners History of inconsistent or no condom use Commercial sex work In high-prevalence area or network HIV-positive injecting partner Sharing injection equipment Recent drug treatment (but currently injecting) CDC, Centers for Disease Control and Prevention; MSM, men who have sex with men; PrEP, pre-exposure prophylaxis; STI, sexually transmitted infection. The CDC recently published PrEP guidelines, and included is a list of who is at greatest risk of acquiring HIV and may consider using daily PrEP for HIV prevention. This includes men who have sex with men and heterosexual men and women with HIV-positive sexual partners and/or high number of sexual partners; having had a recent bacterial sexually transmitted infection; inconsistent or no condom use; commercial sex workers; or living in high-prevalence areas. In addition, they also recommend the use of PrEP for injection drug users who have HIV-positive injecting partners, who share injecting equipment, and who’ve had a recent drug treatment but are currently injecting. CDC. PrEP Guideline

“Ironically, it may require greater intimacy to discuss sex than to engage in it” The Hidden Epidemic Institute of Medicine, 1997 This is a quote from The Hidden Epidemic, and although it was published in 1997, this sentiment is still true. It is difficult for many healthcare providers to engage in discussions about sexual behavior.

Many Patients Want Clinicians to Ask About Sexual Issues
In a survey of adults, 85% expressed an interest in talking to their providers about sexual issues; 71% thought their provider would likely dismiss their concerns[1] In a survey of PCPs, 94% routinely asked patients about smoking, whereas 49% asked about STIs, and 27% about sexual orientation[2] PCP, primary care providers; STI, sexually transmitted infection. We do know that patients would like to talk to providers about sexual issues, and as midlevels we have the responsibility and the relationship with our clients to bridge this gap and make talking about sexual risk part of our practice despite what a person is coming in to talk to us about. 1. Marwick C. JAMA 1999;281: CDC. MMWR Morb Mortal Wkly Rep. 1994;42:

How Do We Decide If a Patient May Be a Candidate for PrEP?
Are they at substantial risk of HIV infection? Are they able to adhere to a once-daily tablet regimen? What is their likely tolerance of possible adverse effects? Are they able to maintain follow-up appointments? Are there any economic issues or other concerns? PrEP, pre-exposure prophylaxis. So how do we decide if a patient may be a good candidate for PrEP? This is not an objective decision, and this should be based on ongoing discussions between you and your patients. Are they at risk? Are they able to take their medications so that they’ll be most effective? Will they have side effects that they won’t tolerate? Will they be able to get the medication and pay for it? What are their copays? These are all things we need to consider. In our patient–provider relationship, we need to have these discussions prior to and during the time in which we’re prescribing PrEP for HIV prevention.

Pre-PrEP Counseling, Testing, and Clinical Evaluation
PrEP, pre-exposure prophylaxis. Let’s focus now on pre-PrEP counseling, testing, and appropriate clinical evaluation.

CDC Guideline: Clinical Eligibility for PrEP
The following are required before prescribing PrEP to identify patients for whom PrEP would be harmful or may present risks to health: Documented negative HIV test result No signs or symptoms of acute HIV infection Normal renal function; no use of contraindicated medications Documented HBV infection status and vaccination status CDC, Centers for Disease Control and Prevention; HBV, hepatitis B virus; PrEP, pre-exposure prophylaxis. The CDC provides thoughtful guidelines about clinical eligibility for PrEP. The following are required before prescribing PrEP to identify patients for whom PrEP would be harmful or may present risks to health. A documented HIV-negative test result without signs or symptoms of acute HIV infection. We also want to see normal renal function, no use of contraindicated medications, and document hepatitis B virus infection status and vaccination status. Tenofovir/FTC has hepatitis B antiviral activity, and cessation of the antiviral medication will cause a viral rebound in patients with hepatitis B. Infrequently, especially in the setting of advanced liver disease, this may cause an acute liver failure as a result of that viral rebound and the subsequent inflammation. CDC. PrEP Guideline

HIV Screening Exclude acute and chronic HIV infection[1,2]
Consider variety of testing methods including 4th-generation HIV Ag/Ab or HIV-1 RNA using nucleic acid–based tests At a minimum, document negative antibody test within the wk before starting PrEP Do not accept patient-reported results Avoid use of oral rapid HIV testing due to lower sensitivity Ab, antibody; Ag, antigen; PrEP, pre-exposure prophylaxis. We want to make sure we screen properly for HIV and exclude both acute and chronic infection. Consider the variety of testing methods, including fourth-generation combination HIV antigen and antibody tests or viral load testing using nucleic acid-based tests. At a minimum, document negative antibody test within the week before starting PrEP. Do not accept patient-reported results, and avoid the use of oral rapid HIV testing due to lower sensitivity. 1. CDC. PrEP Guideline Daar ES, et al. Curr Opin HIV AIDS. 2008;3:10-15.

Acute HIV Infection Patients who are candidates for PrEP are at substantial risk of HIV infection Acute HIV infection should be suspected in patients with recent HIV exposure[1] Signs and symptoms include fever, rash, pharyngitis, lymphadenopathy, myalgia, headache, diarrhea, arthralgia[2] All PrEP candidates with a negative or indeterminate HIV antibody test should be asked about symptoms of viral illness in the previous month or on the day of evaluation Additional confirmatory testing is needed in patients reporting recent signs or symptoms suggestive of acute HIV PrEP, pre-exposure prophylaxis. Acute HIV infection is important to think about. Patients who are candidates for PrEP are at substantial risk for HIV infection. Acute HIV infection should be suspected in patients with recent HIV exposure or potential for exposure. Signs and symptoms include fever, rash, pharyngitis, lymphadenopathy, etc. All PrEP candidates with a negative or indeterminate HIV antibody test should be asked about symptoms of viral illness in the previous month or on the day of evaluation. In the iPrEx trial, drug-resistant virus developed in 2 persons with unrecognized acute HIV infection at enrollment and for whom tenofovir/FTC had been dispensed. These participants had negative antibody test results before they started taking PrEP. They tested positive at a later study visit. Returning to the initial blood specimens using PCR technology during that initial visit found the virus present. 1. CDC. PrEP Guideline Daar ES, et al. Curr Opin HIV AIDS. 2008;3:10-15.

Documenting HIV Status
HIV immunoassay blood test (rapid test if available) Blue = HIV-, eligible for PrEP Consider HIV+ (pending confirmatory testing) Negative Indeterminate Positive Orange = HIV+, not eligible for PrEP Signs/symptoms of acute HIV infection anytime in previous 4 wks Green = HIV status unclear; defer PrEP decision HIV- No Yes Option 1 Option 2 Option 3 Retest antibody in 1 mo; defer PrEP decision Send blood for HIV antibody/antigen assay* Send blood for HIV-1 RNA assay Positive HIV+ VL > 50,000 copies/mL HIV+ FDA, US Food and Drug Administration; PrEP, pre-exposure prophylaxis; VL, viral load. This is a nice algorithm which shows us how we can document HIV status. As we see, we start with an HIV immunoassay blood test, and if that is positive, we would obviously move forward towards confirmatory testing. If the person is negative or indeterminate, we continue on the algorithm. We want to look to see if any signs or symptoms of acute infection are present. I would additionally say we want to ascertain what their risk is for infection as well. And if either are present, we would continue down the algorithm with one of 3 options. The first is to delay PrEP and repeat antibody screening in 1month. Option 2 is to send that blood specimen for our fourth-generation antibody/antigen combination test. And option 3 is to send the blood for HIV-1 viral load study. The time difference between option 2 and 3 is real but minimal, as option 2 with its p24 antigen study will identify HIV infections generally within about 2 weeks and is a very sensitive study. Negative HIV- VL < 50,000 copies/mL Retest VL; defer PrEP decision VL < level of detection; no signs/ symptoms on day of blood draw HIV- *Use only HIV antigen antibody tests that are approved by FDA for diagnostic purposes VL < level of detection with signs/symptoms on day of blood draw; retest in 1 mo; defer PrEP decision CDC. PrEP Guideline

Additional Clinical and Laboratory Evaluation
Evaluate for comorbidities that may complicate PrEP use, such as renal disease or hepatitis, and drug interactions Any person with an estimated CrCl of < 60 mL/min should not be prescribed PrEP with TDF/FTC Document HBV and HCV status before PrEP use; vaccinate patients who are HBV susceptible Comanage HBsAg+ with a hepatologist; monitor for HBV flares Optional assessments Patients with bone disease or significant risk factors for osteoporosis should be referred for appropriate management Therapeutic drug monitoring Metabolic panel, urinalysis, STI, and pregnancy screening CrCl, creatinine clearance; FTC, emtricitabine; HBsAg, hepatitis B surface antigen; HBV, hepatitis B virus; HCV, hepatitis C virus; PrEP, pre-exposure prophylaxis; STI, sexually transmitted infection; TDF, tenofovir. We want to consider other tests beyond infection screening in patients that are considering PrEP. We want to evaluate for comorbidities that may complicate PrEP use, such as renal disease, viral hepatitis, and drug interactions. Any person with an estimated creatinine clearance of less than 60 should not be prescribed PrEP with tenofovir/FTC. Document hepatitis B and hepatitis C status before PrEP use, and vaccinate patients who are hepatitis B susceptible. And those patients who live with hepatitis B, we want to consider managing them properly with a hepatologist—someone who can help us monitor for hepatitis B flares and properly assess the patient if that were to occur. There are optional assessments. Patients with bone disease or significant risk factors for osteoporosis should be referred for appropriate management. Therapeutic drug monitoring in certain settings is an option to help evaluate adherence and absorption. And we may also consider a metabolic panel, urinalysis, STI, and pregnancy screenings, when appropriate. CDC. PrEP Guideline

Adverse Events Inform patients about AEs observed in HIV-uninfected participants in PrEP trials[1] iPrEx: small but significant early nausea and weight loss[2] Potential bone and renal toxicity Known risk associated with TDF Potential for other serious AEs with long-term use However, TDF/FTC commonly used in HIV infection Potential for drug-resistant HIV infection Infrequent in clinical trials but must exclude HIV infection AE, adverse event; FTC, emtricitabine; PrEP, pre-exposure prophylaxis; TDF, tenofovir. We must encourage our patients to think about the risk and benefit of PrEP because that conversation is likely going to evolve as their risks change and their health changes. We want to inform patients about adverse events observed in HIV-uninfected participants in PrEP trials. Fortunately, these adverse events have been mild and not frequently reported. In the iPrEx trial, for example, there was a small but statistically significant side effect of early nausea which likely led to some small weight loss. As we know, tenofovir is associated with bone and renal toxicity, and there is the potential for other serious adverse effects with long-term use. When counseling my patients, I often tell them about my experience with HIV therapy. I reassure them that tenofovir and FTC has been prescribed for many years in people living with HIV, and we have a lot of confidence in our knowledge of the medication. But I do explain that there are some areas where understanding is lacking. For example, I’ll say that men and women living with HIV often have many chronic health problems, and while HIV is likely the cause for that, we’re uncertain how much medications such as tenofovir and FTC contribute to that. So there is some acceptance on the part of the patient as to the potential for other adverse effects, especially with long-term use, and as was shown earlier, the potential for drug-resistant HIV infection if somebody had unrecognized acute HIV infection when they started taking PrEP. 1. CDC. PrEP Guideline Grant RM, et al. N Engl J Med. 2010;363:

Adherence Counseling Adherence counseling.

CDC Guideline: Recommended PrEP Regimen
Fixed-dose TDF/FTC is the recommended PrEP regimen for MSM, heterosexually active men and women, and IDU who meet PrEP prescribing criteria Dosed as a single pill (300/200 mg) once daily This regimen is approved by the FDA for PrEP use Provide a prescription or refill for no more than 90 days TDF alone may be considered as an alternative for IDU and heterosexually active men and women (but not MSM) Based on efficacy data from clinical trials This regimen is NOT approved by the FDA for PrEP use CDC, Centers for Disease Control and Prevention; FDA, US Food and Drug Administration; FTC, emtricitabine; IDU, injection drug users; MSM, men who have sex with men; PrEP, pre-exposure prophylaxis; TDF, tenofovir. Fixed-dose tenofovir/FTC is the recommended PrEP regimen for men who have sex with men, heterosexually active men and women, and intravenous drug users who meet PrEP prescribing criteria. It is dosed as a single pill taken once daily. This regimen is approved by the FDA for PrEP use. Provide a prescription or refill for no more than 90 days to ensure follow-up and contact with the patient. Tenofovir alone may be considered as an alternative for intravenous drug users and heterosexually active men and women, but not the MSM community at this point, based on efficacy data from clinical trials. This regimen, by the way—tenofovir alone is not approved by the FDA for PrEP use. CDC. PrEP Guideline

HIV Incidence and Drug Concentrations HIV Incidence per 100 Person-Yrs
Oral PrEP Reduces Incidence of HIV in MSM, Even With Incomplete Adherence iPreX OLE: open-label extension of iPrEX trial of daily TDF/FTC oral PrEP in MSM and transgender women (N = 1603) 100% adherence was not required to attain full benefit from PrEP Benefit of 4-6 tablets/wk similar to 7 tablets/wk 2-3 tablets/wk also associated with significant risk reduction Higher levels of sexual risk taking at baseline were associated with greater adherence to PrEP HIV Incidence and Drug Concentrations 5 4 3 2 1 < 2 Tablets/Wk 2-3 Tablets/Wk 4-6 Tablets/Wk 7 Tablets/Wk Off PrEP HIV Incidence per 100 Person-Yrs On PrEP FTC, emtricitabine; MSM, men who have sex with men; PrEP, pre-exposure prophylaxis; TDF, tenofovir; TFV-DP, tenofovir diphosphate. In the iPrEx open-label extension study of tenofovir/FTC in men who have sex with men and transgender women, we found that 100% adherence was not required to attain full benefit from PrEP. The benefit of 4-6 tablets a week was similar to 7 tablets a week, and 2-3 tablets a week was also associated with a significant risk reduction, although not as strong. We also found that higher levels of sexual risk taking at baseline were associated with greater adherence to PrEP. 1500 1250 1000 700 500 350 LLOQ TFV-DP in fmol/punch Follow-up Risk Reduction 95% Cl 26% 44% -31 to 77% 12% 84% 21 to 99% 21% 100% 12% 100% 86 to 100% (combined) 1. Grant R, et al. IAC Abstract TUAC0105LB. 2. Grant R, et al. Lancet Infect Dis. 2014;14:

iPrEX OLE: HIV Infection Occurred During Gaps in PrEP Use
First evidence of HIV infection 1.0 0.8 0.6 0.4 0.2 TFV-DP LLOQ TFV-DP ≥ 350 fmol/punch Control Proportion With TFV-DP Detected in Dried Blood Spots Case Control Case LLOQ, lower limit of quantification; PrEP, pre-exposure prophylaxis; TFV-DP, tenofovir diphosphate. This slide further identifies the importance of adherence in the iPrEx open-label study. Here we look at 2 participants who became infected with HIV and that were matched with similar controls by site of study, age, etc. And this demonstrates HIV infection emerges in this setting of reduced drug levels, and these drug levels were obtained through dried blood spot evaluation of tenofovir. 72 60 48 36 24 12 Wks Preinfection Wks Postinfection Control, n: Case, n: 380 8 768 7 386 266 171 44 1. Grant R, et al. IAC Abstract TUAC0105LB. Reprinted with permission. 2. Grant R, et al. Lancet Infect Dis. 2014;[Epub ahead of print].

Key Components of Medication Adherence Counseling
Address adverse events[1] Identify barriers to adherence[1] Respond to missed doses with normalization and nonjudgement, and emphasize importance of adherence[1] Patient self-reporting may not reflect actual adherence[2,3] Key components of medication adherence counseling include addressing adverse effects. So if somebody’s having persistent nausea, altered bowel movements, we want to try and identify ways in which we can reduce that adverse effect burden. We want to identify barriers to adherence, which may include shift work issues such as our case or logistical issues—getting to the pharmacy—financial issues with copayments, etc. Respond to missed doses with normalization, nonjudgment, and emphasize the importance of adherence. Keep in mind, patient self-reporting of adherence may not reflect actual adherence. We can use other methods for this, although many are not available in the clinical realm, and that includes therapeutic drug monitoring, and also pharmacy reporting of prescription refills. 1. CDC. PrEP Guideline Van Der Straten A, et al. CROI Abstract Baxi SM, et al. CROI Abstract 953.

On-Treatment Follow-up
Let’s move forward with on-treatment follow-up

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* CDC, Centers for Disease Control and Prevention; PrEP, pre-exposure prophylaxis; STI, sexually transmitted infection. Patients should be returning for follow-up at least every 3 months. Consider a visit initially after 1 month to assess HIV status, adverse effects, or patient concerns. With all patients, at least every 3 months we want to screen for HIV, offer medication adherence counseling, and behavioral risk reduction support. We want to evaluate for side effects and also sexually transmitted infection symptoms, especially those of HIV. After 3 months and at least every 6 months thereafter, assess renal function. At least every 6 months, test for bacterial sexually transmitted infections, and at least every 12 months, evaluate the need to continue PrEP. With women, we want to test for pregnancy when appropriate. And in those patients living with hepatitis B, every 6-12 months, we want to be doing an HBV DNA quantitative assay. And in the event of viral rebound, we want to make sure we are evaluating the health of the liver and patient status properly. My first visit with a patient when we are about to start PrEP includes not only an agreement that the patient accept the potential adverse effects and adherence but also agrees to follow-up on PrEP; I really identify it as a significant commitment on their part. And I identify myself as an ally to support them through this as much as possible, but really for that person’s own health, 3 months is very important for follow-up. *Every 6-12 mos. CDC. PrEP Guideline

Responding to Patient-Reported Challenges
Discuss management of common adverse events; most will diminish within the first few wks of treatment[1] Patients may report feeling stigmatized by peers and medical providers for their use of PrEP[2] Issues related to medication access should be addressed promptly PrEP, pre-exposure prophylaxis. Let’s talk about responding to patient-reported challenges. First, we want to discuss the management of common adverse events with patients even before they start PrEP and really emphasize that most will diminish within the first few weeks of starting treatment. We often refer to this as the start-up syndrome. And if there’s nausea, we may encourage patients to take the medicine with food and/or before going to bed at night. And there are also medications which can sometimes be prescribed if the nausea is particularly burdensome. Patients may report feeling stigmatized by peers and medical providers for their use of PrEP, and I’ve heard this from a number of patients utilizing these medications. And I think it’s important that we empower patients to identify a healthcare team which is affirming towards their particular situation. And I think in patients who are identifying stigma from peers, I think we should in a way congratulate our patients for taking ownership of their health and being comfortable discussing this issue. As we identified before, there’s certainly a lack of awareness among the community about PrEP. Issues related to medication access should be addressed promptly, and this may include financial, logistical reasons. As a clinician, I don’t always have the answer to this, but I can at least be empathetic and try and direct someone to a pharmacist or a pharmaceutical company payment assistance program that can be of greater assistance. 1. CDC. PrEP Guideline Liu A, et al. PLoS Med. 2014;11:e

PrEP Trials Found Decreasing Risk Behavior Over Time
iPrEx[1] Partners PrEP[2] 100 80 Placebo 50 Placebo TDF/FTC TDF/FTC 40 TDF 60 Subjects Reporting Unprotected Receptive Anal Sex (%) 30 Subjects Reporting Unprotected Sex (%) 40 20 20 FTC, emtricitabine; PrEP, pre-exposure prophylaxis; TDF, tenofovir. PrEP trials have found decreasing risk behavior over time. This counters what many thought would occur, a phenomenon known as risk compensation. So taking PrEP reduces risk towards HIV, and as a result, individuals may increase risky behavior, whether it be through unprotected sex or numbers of sexual partners. These 2 graphs suggest reduced risky behavior in 2 randomized clinical trials. The iPrEx and Partners PrEP trial showed decreased unprotected sex. However, these trials were placebo controlled, so the participants may have been uncertain if they were taking an active agent or not. Additionally, these randomized clinical trials came with a significant amount of behavioral counseling and education which may not be available in a real-world setting. 10 24 48 72 96 120 144 3 6 9 12 15 18 21 24 27 30 33 Wks Since Randomization Follow-up Time (Mos) 1. Grant RM, et al. N Engl J Med. 2010;363: 2. Baeten JM, et al. N Engl J Med. 2012;367:

Pregnancy PrEP use at conception and during pregnancy by the uninfected partner may offer an additional tool to reduce the risk of sexual HIV acquisition[1] Data directly related to the safety of PrEP use for a developing fetus are limited Potential risks and limited information should be discussed TDF and FTC are classified as FDA Pregnancy Category B medications[2] FDA, US Food and Drug Administration; FTC, emtricitabine; PrEP, pre-exposure prophylaxis; TDF, tenofovir. PrEP use at conception and during pregnancies by the uninfected partner may offer an additional tool to reduce the risk of sexual HIV acquisition. Data directly related to the safety of PrEP use for a developing fetus are limited. Potential risks and limited information should be discussed. Tenofovir and FTC are classified as FDA Pregnancy Category B medications. In the PrEP trials with heterosexual women, these medications were promptly discontinued for those who became pregnant, so the safety for exposed fetuses could not be adequately assessed. A single small study of periconception use of tenofovir in 46 uninfected women in HIV-discordant couples found no ill effect on the pregnancy and no HIV infections. Additionally, tenofovir and FTC are widely used for the treatment of HIV infection and continued during pregnancies that occur, the data on pregnancy outcomes in the Antiretroviral Pregnancy Registry provide no evidence of adverse effect among fetuses exposed to these medications. 1. CDC. PrEP Guideline DHHS. HIV Perinatal Guideline

Stopping PrEP Lack of guidance on when to stop PrEP in relationship to exposures Reasons to stop PrEP: Evidence of HIV infection Pregnancy Adverse events Chronic nonadherence Patient choice If resuming PrEP after stopping, repeat standard pre-PrEP evaluation PrEP, pre-exposure prophylaxis. There is a lack of guidance on when to stop PrEP in relationship to an exposure. There are a number of reasons to stop PrEP: Evidence of HIV infection is one of them; pregnancy; adverse effects, including renal failure; chronic nonadherence should definitely be an issue brought up with our patients, especially since they may not be receiving much benefit at all if the adherence is below the thresholds previously discussed; and patient choice to stop. If resuming PrEP after stopping, repeat the standard pre-PrEP evaluation. CDC. PrEP Guideline

Conclusions

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, acute and chronic HIV infection must be excluded, and the patient assessed for comorbidities that may present health risks The recommended PrEP regimen is fixed-dose TDF/FTC Patients prescribed PrEP should return for follow-up visits at least every 3 mos FTC, emtricitabine; IDU, injection drug users; MSM, men who have sex with men; PrEP, pre-exposure prophylaxis; TDF, tenofovir. In conclusion, PrEP is recommended as one prevention option for sexually active men who have sex with men, heterosexual men and women, and injection drug users who are at substantial risk of HIV acquisition. Adherence to PrEP is a key factor in the efficacy of this method. Before, as providers, we begin to prescribe PrEP, we want to assess for acute and chronic HIV infection, and we must exclude these. We also want to assess our patients for comorbidities that may be present as health risks for them using these medications to prevent HIV. The recommended PrEP regimen is fixed-dose tenofovir/FTC, and patients prescribed PrEP should return for follow-up visits at least every 3 months.

Resources for Healthcare Professionals
CDC PrEP Guideline: Clinical Providers’ Supplement[1] Patient information sheets Patient/provider checklist MSM risk index screening tool Centers for Disease Control and Prevention[2] PrEP patient information sheets CDC, Centers for Disease Control and Prevention; PrEP, pre-exposure prophylaxis. We’ve included some resources for healthcare professionals to use as you begin or consider using PrEP in your practice to support your patients to prevent HIV.

Go Online for More Educational Content on PrEP in HIV!
Interactive Virtual Presentation featuring streaming narration of these slides and case studies illustrating PrEP decisions by expert faculty Marcy S. Gelman, RN, MSN, MPH, and Kevin M. O’Hara, PA ClinicalThought™ with expert faculty commentaries on PrEP in HIV clinicaloptions.com/midlevel

Why, When, and How to Use Pre-Exposure Prophylaxis (PrEP) for HIV Acquisition: Guidance for Midlevel Practitioners Marcy S. Gelman, RN, MSN, MPH Director.

Similar presentations

Presentation on theme: "Why, When, and How to Use Pre-Exposure Prophylaxis (PrEP) for HIV Acquisition: Guidance for Midlevel Practitioners Marcy S. Gelman, RN, MSN, MPH Director."— Presentation transcript:

Similar presentations

About project

Feedback

Log in

Auth with social network:

Why, When, and How to Use Pre-Exposure Prophylaxis (PrEP) for HIV Acquisition: Guidance for Midlevel Practitioners Marcy S. Gelman, RN, MSN, MPH Director.

Similar presentations

Presentation on theme: "Why, When, and How to Use Pre-Exposure Prophylaxis (PrEP) for HIV Acquisition: Guidance for Midlevel Practitioners Marcy S. Gelman, RN, MSN, MPH Director."— Presentation transcript:

Similar presentations

About project

Feedback