Pre-Exposure Prophylaxis against HIV in Primary Care. September 2017 Update. John-Paul Bettencourt, D.O., M.P.H., AAHIVS

Transcription

1 John-Paul Bettencourt, D.O., M.P.H., AAHIVS Pre-Exposure Prophylaxis against HIV in Primary Care September 2017 Update

2 Continuing Medical Education Disclosure Program Faculty: John-Paul Bettencourt, DO, MPH, AAHIVS Financial Disclosure: No relationships or conflicts. Off-Label Use: This presentation does not include off-label products or treatments.

3 tinyurl.com/ 2017UNECOM

4 Informing Guidelines Centers for Disease Control and Prevention: US Public Health Service: Preexposure Prophylaxis for the Prevention of HIV Infection in the United States 2014 Clinical Practice Guideline Centers for Disease Control and Prevention: US Public Health Service: Preexposure prophylaxis for the prevention of HIV infection in the United States 2017 Update: a clinical practice guideline. Updated September Centers for Disease Control and Prevention: US Public Health Service: Preexposure prophylaxis for the prevention of HIV infection in the United States 2014: clinical providers supplement. Centers for Disease Control and Prevention: US Public Health Service: Preexposure prophylaxis for the prevention of HIV infection in the United States 2017 Update: clinical providers supplement. Updated September 2017.

5 Case Study Joe is a 27 year-old generally healthy male presents to establish care. 2 day Hx of acute onset cold with fever, sore throat, and swollen glands with multiple sick contacts at work, no flu shot Tx with frequent ibuprofen MSM with unprotected anal sex with 1 primary and 2 occasional sex partners Last unprotected sexual encounter 10 days ago 4 th Gen HIV Ab/Ag test negative Next step?

6 Objectives Review current demographics of at-risk populations and current trends of new HIV Infections Review Indications, Testing/Timeline, and Refill protocols for PrEP against HIV medication Review Non-Occupational Post Exposure Prophylaxis (npep) protocol if patient is exposed to HIV Briefly review current state of HIV Treatment

7 Signs and Symptoms of Acute HIV Fever 75% Fatigue 68% Myalgia 49% Skin rash 48% Headache 45% Pharyngitis 40% Cervical LAD 39% Arthralgia 30% Night sweats 28% Diarrhea 27%

8 Current state of HIV 1.1 million people in the US are living with HIV 15% of them don t know it. Young people were the most likely to be unaware of their infection. 44% of y/o did not know they were living with HIV. CDC. Singh S, Song R, Johnson AS, McCray E, Hall HI. HIV incidence, prevalence, and undiagnosed infections in men who have sex with men. Presented at Conference on Retroviruses and Opportunistic Infections; February 14, 2017; Seattle, WA.

9 New HIV Infections 39,513 new HIV infections (2015) 67% were among homosexual (MSM) or bisexual (MSWM) 24% were among heterosexual (MSW/WSM) 3% were among people who inject drugs (PWID)

10 From 2010 to 2014: Overall estimated number of annual HIV infections declined 10% Among PWID, annual infections declined 32% Among heterosexuals, annual infections declined 23%. Among gay and bisexual men, trends varied by race and age: White gay/bisexual men: declined 11%. Black/African American gay/bisexual men: infections remained stable. Hispanic/Latino gay/bisexual men: increased 14%. Gay and Bisexual men aged 13-24: Declined 16% Gay and Bisexual men aged 25-34: Increased 23% Gay and Bisexual men aged 35-44: Declined 16%

11 New HIV Diagnoses in the United States for the Most-Affected Subpopulations, 2015 (CDC)

12 Time to act Each year, approximately 50,000 people are diagnosed with HIV infection in the United States, and many others are at risk Men who have sex with men and transgender women face an especially high risk of becoming infected with HIV. This is an opportunity to prevent HIV by offering preexposure prophylaxis (PrEP) to people with a high risk of infection.

13 What is PrEP against HIV? A biomedical intervention consisting of a daily, oral antiretroviral medication that is >90% effective if taken regularly by people who are HIV-uninfected but at risk of infection Currently, the only medication licensed for PrEP in the United States is the once-daily tablet tenofovir disoproxil fumarateemtricitabine (TDF-FTC, also called Truvada). Other PrEP medications and formulations are being developed, but they are not yet available for clinical use in the United States.

14 Who is high risk? Men who have Sex with Men (MSM) Condomless anal sex Recent sexually transmitted infection HIV-infected partner Heterosexual adults Condomless sex with a partner who injects drugs Comdomless sex with a bisexual man HIV-infected partner Injection drug users Use of shared injection equipment Preexposure prophylaxis for the prevention of HIV infection in the United States CDC. Available from:

15 How well does PrEP work?

16 PrEP Clinical Trial Results iprex Study: Among gay and bisexual men, those who were given PrEP were 44% less likely overall to get HIV than those who were given a placebo. Of participants with detectable levels of medicine in their blood, PrEP reduced the risk of infection by as much as 92%. ( Partners PrEP Study: Among men and women in HIV discordant couples, those who received PrEP were 75% less likely to become infected than those on placebo. Among those with detectable levels of medicine in their blood, PrEP reduced the risk of HIV infection by up to 90%. ( Bangkok Tenofovir Study: Among injection drug users, a once-daily tablet containing tenofovir (one of the two drugs prescribed in Truvada) reduced the risk of getting HIV by 49%. For participants who had detectable tenofovir in their blood, risk of infection reduced by 74%. ( No significant safety concern with use of daily oral PrEP was found in any study.

17 History July 2012: FDA approves the combination pill Truvada for use as PrEP. Gilead Sciences report on the estimated number of U.S. residents going on PrEP for the first time per quarter between 2012 and (FTC/TDF is shorthand for Truvada.) Note the steady increase launching in late 2013.Gilead Sciences.

18 Use of PrEP against HIV >79,000 people in the US have started Truvada Mean age was 36 years California, New York, Texas, Florida and Illinois accounted for just over half of all prescriptions But a smaller state Massachusetts had the highest percentage of its residents on PrEP, at 0.073%

19 How are we doing? 1.2 million Americans are likely to benefit from using HIV pre-exposure prophylaxis (PrEP) 1 in 4 sexually active MSM...492,000 1 in 5 persons who inject drugs 115,000 1 in 200 heterosexual adults..624, million Americans are indicated to use PrEP against HIV BUT ARE NOT TREATED Smith MMWR 2015; McCallister IAS 2016

20 What that means 1,200,000 people indicated for PrEP 79,000 people are prescribed

21 How to Prescribe PrEP against HIV

22 Determine eligibility for PrEP against HIV Document high risk of HIV infection based sexual and medical history. Assess ability/willingness to adhere to regular visits, testing, and daily medication. Confirm that the patient is HIV-uninfected preferably a fourth-generation HIV antibody-antigen test. No s/s of acute HIV infection in the previous 4 weeks Positive symptoms HIV RNA ( viral load ) Confirm that creatinine clearance >60 ml/min Assess for chronic hepatitis B infection by sending a hepatitis B surface antigen test (HBsAg). Assess pregnancy status in patients with childbearing potential.

23 ASSESSING RISK OF SEXUAL HIV ACQUISITION 76% of MSM surveyed in 2008 in 21 US cities reported a health care visit during the past year BUT studies report that health care providers do not ask about, and patients often do not disclose, same-sex or high-risk sexual behaviors. Were you sexually active within the past 6 months? With males, females, or both? What % of the time was a condom used? Do you practice ANY anal sex?

24 Oral PrEP Knowledge and Experience 2016 MSM online survey, n=4,638 Heard of PrEP 78.2% Taken PrEP 14.9% Ability to adhere to PrEP Very easy 80.0% Somewhat easy 11.4% Somewhat or very difficult 4.0%

25 Prescribe PrEP against HIV Prescribe once-daily, oral fixed-dose combination tablet Truvada consisting of 300 mg of tenofovir disoproxil fumarate and 200 mg of emtricitabine (TDF-FTC) CDC recommends prescribing no more than a 90-day supply so that patients do not continue the medication long term without appropriate clinical and laboratory monitoring.

26 Patient Instructions for Truvada Take as a daily dose No diet change required If dose is forgotten, take as soon as remembered unless it is almost time for the next dose (DO NOT DOUBLE DOSE) Take on a full stomach or before bed

27 Truvada Risks Kidney problems, including kidney failure. Your healthcare provider may do blood tests to check your kidneys before and during treatment with TRUVADA. If you develop kidney problems, your healthcare provider may tell you to stop taking TRUVADA. Too much lactic acid in your blood (lactic acidosis), which is a serious but rare medical emergency that can lead to death. Tell your healthcare provider right away if you get these symptoms: weakness or being more tired than usual, unusual muscle pain, being short of breath or fast breathing, stomach pain with nausea and vomiting, cold or blue hands and feet, feel dizzy or lightheaded, or a fast or abnormal heartbeat. Severe liver problems, which in rare cases can lead to death. Tell your healthcare provider right away if you get these symptoms: skin or the white part of your eyes turns yellow, dark "tea-colored" urine, light-colored stools, loss of appetite for several days or longer, nausea, or stomach-area pain. Bone problems, including bone pain, softening, or thinning, which may lead to fractures. Your healthcare provider may do tests to check your bones. Worsening Hepatitis B infection

28 Risks - BONE HEALTH Decreases in bone mineral density (BMD) have been observed in HIV-infected persons treated with combination antiretroviral therapy (including TDF-containing regimes) Studies show a ~2% decrease in bone density with no increase in fragility (atraumatic) fractures over the 1-2 years of observation Therefore, DEXA scans or other assessments of bone health are NOT recommended before initiation, or monitoring, of persons taking PrEP However, any person being considered for PrEP who has a history of pathologic or fragility bone fractures or who has significant risk factors for osteoporosis should be referred for appropriate consultation and management.

29 Costs to the Patient PrEP against HIV is covered by most insurances Gilead Sciences has an Assistance Program Annual Out-of-Pocket expenses include at least four office visit (preventive counseling), lab, and prescription co-pays In 2012, NY DOH estimated that Truvada for PrEP costs $8,000-$14,000 per year (

30 Truvada Side Effects Nausea/Diarrhea/Flatulence (abdominal pain/weight loss) Rash Headache/Dizziness Abnormal dreams/problems sleeping/tiredness Depression Symptoms usually resolve within 2 weeks to 2 months Only 44% of PrEP users reported any side effects

31 Monitor PrEP against HIV Send an HIV antibody/antigen test at least every 3 months. Suspicion for acute HIV infection HIV RNA Viral Load Check pregnancy status every 3 months. There are no known safety concerns with PrEP use in pregnancy; however, data on this subject are limited. Check a serum creatinine after 3 months and, if stable, every 6 months thereafter. Perform STI screening (syphilis antibody, nucleic acid amplification testing for gonorrhea and chlamydia at all sites that could have been exposed) at least every 6 months. Evaluate continued appropriateness for PrEP on at least an annual basis.

32 Follow-up Office visits Patients should return for follow-up every 3 months. I recommend pre-scheduling at least 2 visits (6 months) Clinicians may wish to see patients more frequently at the beginning of PrEP 1 month after initiation, to assess and confirm HIV-negative test status, assess for early side effects, discuss any difficulties with medication adherence, and answer questions. Clinicians may wish to see patients more frequently who are engaged in multiple high-risk behaviors.

33 Mitigate Risks Counsel about adherence to protocol and risk reduction at every visit. Recommend reduction in sexual partners Recommend reduction in other high risk behaviors (EtOH abuse, illicit drug use, sex work, trauma-inducing sexual activity) Reassess the need for PrEP against HIV at least once per year PRACTICE SAFE SEX!!!

34 HIV Testing Documentation of results are required to confirm that patients do not have HIV infection when they start taking PrEP medications. For patient safety, HIV testing should be repeated at least every 3 months (before prescriptions are refilled or reissued). This requirement should be explained to patients during the discussion about whether PrEP is appropriate for them. CDC & USPHTF recommend that MSM, IDUs, patients with a sex partner who has HIV infection, and others at substantial risk of HIV acquisition undergo an HIV test at least annually or for those with additional risk factors, every 3-6 months. Outside the context of PrEP delivery, testing is often not done as frequently as recommended.

35 HIV Testing At a minimum, clinicians should document a negative antibody test result within the week before initiating (or reinitiating) PrEP medications. The required HIV testing can be accomplished by (1) drawing blood (serum) and sending the specimen to a laboratory for a routine HIV EIA (enzyme-linked immunoassay) or (2) performing a rapid, point-of-care, FDA-approved, fingerstick blood test. Oral rapid tests should not be used to screen for HIV infection when considering PrEP use because they can be less sensitive than blood tests. Clinicians should not accept patient-reported test results or documented anonymous test results. A preliminary positive HIV antibody test must be confirmed by Western blot or IFA (immunofluorescence assay) according to the local laboratory standard practice and viral load and CD4 lymphocyte tests should be ordered to assist in future treatment decisions.

36 HIV Resistance iprex Treatment Group iprex Control Group 2 infected at baseline 2 resistant viruses 8 infected at baseline 1 resistant virus 36 infected after baseline 0 resistant viruses 64 infected after baseline 0 resistant viruses

37 PrEP Failures 43-yr-old MSM 24 mos, supported by pharmacy records, blood concentration analyses, and clinical history Acquired MDR HIV infection Exposure to PrEP-resistant, multiclass-resistant HIV strain MSM in his 20s Excellent compliance by self report, supported by blood and hair concentration analyses Acquired MDR HIV infection after 2 instances of condomless insertive anal intercourse with 2 different partners within 11 weeks before diagnosis Exposure to PrEP-resistant, multiclass-resistant HIV strain 50-yr-old MSM Excellent by self report, supported by blood analyses Acquired wild-type HIV infection after 2-5 median condomless anal sex partners per day in each month following PrEP initiation Chronic rectal inflammation +/- Trauma Knox DC, et al. CROI Abstract 169aLB.; Grossman H, et al. HIVR4P Abstract OA03.06LB.; Hoornenborg E, et al. CROI Abstract 953

38 Do NOT use other antiretroviral regimens or other medications in lieu of Truvada other than daily dosing of Truvada e.g., intermittent, episodic [pre/post sex only], or other discontinuous dosing PrEP as expedited partner therapy i.e., do not prescribe for an uninfected person not in your care other renal active medications in excess. Acyclovir, valacyclovir, cidofovir, ganciclovir, valganciclovir, aminoglycosides, high-dose or multiple NSAIDS or other drugs that reduce renal function or compete for active renal tubular secretion Serum concentrations of these drugs and/or TDF may be increased. Monitor for dose-related renal toxicities.

39 TIME TO ACHIEVING PROTECTION Maximal protection against HIV infection is unknown. There is not scientific consensus on what intracellular concentrations are protective for either drug or the protective contribution of each drug in specific body tissues. The pharmacokinetics of TDF and FTC vary by tissue. Pharmacokinetic studies suggest maximum tissues levels occur in: rectal tissue after approximately 7 days blood and cervicovaginal tissues after approximately 20 days No data are yet available about intracellular drug concentrations in penile tissues susceptible to HIV infection

40 My talking points with a new patient PrEP efficacy and importance of adherence Side effects: GI, renal, bone PrEP does not protect against other STIs except perhaps HSV (Celum, Ann Intern Med, 2014). Periodic HIV testing, creatinine checks, and office visits are mandatory. The risk of HIV drug resistance if he/she becomes infected with HIV while on PrEP What we think about time to maximal protection, time to continue after last high-risk encounter 40

41 My talking points with a new patient Nausea may occur with initiation of tenofovir-emtricitabine; it typically resolves with time. Kidney injury occurs rarely (2% in iprex). Periodic monitoring is obligatory. Abnormalities usually resolve with drug discontinuation. A small decrease in bone mineral density may occur; the clinical significance of this is unknown. Antiretroviral resistance is unlikely but possible and so strict adherence to the testing/visit protocol is critical PrEP is ONLY PART of the answer to reduce the risk of HIV transmission

42 Efficacy with 95% CI Adherence is Key Any >50% >90% + Drug Levels Compliance with Daily Dosing iprex

43 Improving Compliance with PrEP Monitor medication adherence in a non-judgmental manner Normalize occasional missed doses, while ensuring patient understands importance of daily dosing for optimal protection Reinforce success Assess side effects and plan how to manage them Identify and address factors that interfere with adherence Use a multidisciplinary/team approach (reminders at nursing visits, etc.)

44 Discontinuing PrEP Patients may discontinue PrEP medication for several reasons personal choice, changed life situations resulting in lowered risk of HIV acquisition, intolerable toxicities, chronic nonadherence to the prescribed dosing regimen despite efforts to improve daily pill-taking, or acquisition of HIV infection. Upon discontinuation document in the health record: HIV status at the time of discontinuation Reason for PrEP discontinuation Recent medication adherence and reported sexual risk behavior If resuming PrEP, repeat all the same pre-prescription evaluations as the initial workup.

45 Non-Occupational Post Exposure Prophylaxis (npep) Persons not receiving PrEP who seek care within 72 hours after an isolated sexual or injection-related HIV exposure should be evaluated for the potential need for npep. If such exposures are not isolated, and the person is determined not to have HIV infection, clinicians should consider beginning PrEP immediately because PrEP during the first 28 days is consistent with a recommended npep regimen.

46 Non-Occupational Post Exposure Prophylaxis (npep) If the exposure is isolated (e.g., sexual assault, infrequent condom failure), npep should be prescribed, but continued antiretroviral medication is not indicated after completion of the 28-day PEP course. Persons who repeatedly seek npep should be evaluated for possible PrEP use after confirming they have not acquired HIV infection. Because HIV infection has been reported in association with exposures soon after an npep course, daily PrEP may be more protective than repeated episodes of npep.

47 npep + PrEP Patients fully adhering to a daily PrEP regimen do not need npep if they experience a potential HIV exposure while on PrEP. PrEP is highly effective when taken daily or near daily For patients who report that they take their PrEP medication sporadically and those who did not take it within the week before the recent exposure, initiating a 28-day course of npep might be indicated All npep baseline and follow-up laboratory evaluations should be conducted. After the 28-day npep regimen is completed, if confirmed to be HIV uninfected, the daily PrEP regimen can be reinitiated.

48 npep Protocol

49 Future of PrEP Against HIV Injectable PrEP Daily oral Truvada vs. injectable Cabotegravir 4 year-long study The study is enrolling 18+ y/o HIV uninfected cisgender MSM and transgender women The Fenway Institute is 45% enrolled (although this changes nearly daily!) and enrollment is competitive so enrollment will continue past goal. AMP: Antibody Mediated Prevention Laboratory-made antibodies, modeled after antibodies produced naturally by long-term non-progressors 2 years long and involves 10 IV infusions of the antibodies The study is open to cisgender MSM and transpeople who have sex with men who are HIV uninfected and years old. The Fenway Institute is 95% enrolled and has put a hold on new screening visits. Discover: Comparing daily oral Truvada (FTC/TDF) vs Descovy (FTC/TAF) Descovy is FDA-approved for HIV treatment, but not yet for PrEP. 2 year long with an optional 3 rd year unblinded phase in which participants have the option to stay on Descovy for PrEP for an additional year (contingent on FDA approval). Descovy may have fewer side effects than Truvada. The study is no longer enrolling new participants.

50 Modern HIV Treatment

51 Modern HIV Treatment 20-year-old newly diagnosed HIV-positive adult started immediately on ART has a life expectancy approaching that of the general population Antiretroviral therapy (ART) using a preferred regimen is recommended for all HIV-infected individuals, regardless of CD4 T-lymphocyte cell count, to reduce the morbidity and mortality associated with HIV infection (Samji, H, Cescon, A, Hogg, RS et al. Closing the gap: increases in life expectancy among treated HIV-positive individuals in the United States and Canada. PLoS One. 2013; 8: e81355)

52 Summary PrEP prescribing guidelines US Public Health Service. Preexposure prophylaxis for the prevention of HIV infection in the United States Available from:

53 A pill a day keeps HIV away

54 South Africa

55 South Africa

56 South Africa

57 A pill a day keeps HIV away