Pre-exposure Prophylaxis (PrEP) Non-occupational Post-exposure Prophylaxis (npep) Jeffrey Beal, MD, AAHIVS Florida Health Lee County

Transcription

1 Pre-exposure Prophylaxis (PrEP) Non-occupational Post-exposure Prophylaxis (npep) Jeffrey Beal, MD, AAHIVS Florida Health Lee County Division of Disease Control and Health Protection To protect, promote and improve the health of all people in Florida through integrated state, county and community efforts.

2 Faculty Disclosure In compliance with ACCME Guidelines, I hereby declare: I do not have financial or other relationships with the manufacturer(s)of any commercial services(s) discussed in this educational activity. 2

3 Discussion Topics Data review Describe why PrEP and npep are components of Florida s plan to eliminate HIV transmissions and reduce HIV-related deaths Outline assessment/management of PrEP/nPEP Provide resources for education and support for PrEP and npep programs Florida Department of Health HIV/AIDS Section Division of Disease Control and Health Protection To protect, promote and improve the health of all people in Florida through integrated state, county, and community efforts. Created: 12/15/15 Revised: 03/31/16 3

4 National HIV Surveillance System Census Data Estimating the Lifetime Risk of HIV Diagnosis in the U.S. Mortality Data from National Center for Health Statistics ( , US census data) Methods: HIV diagnoses and non-hiv deaths used to calculate the probability of HIV diagnosis at a given age Lifetime risk = cumulative probability of HIV diagnosis from birth (results presented as 1 in N) Results: Lifetime Risk of Acquiring HIV Overall in USA: 1 in 99 Black MSM: 1 in 2 Hispanic MSM: 1 in 4 White MSM: 1 in 11 Lifetime Risk of an HIV Diagnosis by US State 54 HIV Risk Group Relative Risk Lifetime Risk Male vs female 4X for male 1 in 62 (2%) vs 1 in 221 (0.5%) Male: black vs white 7X for black male 1 in 20 (5%) vs 1 in 132 (1%) Female: black vs white 19X for black female 1 in 48 (2%) vs 1 in 880 (0.1%) Male: IDU vs heterosexual 13X for PWID 1 in 36 (3%) vs 1 in 473 (0.2%) MSM vs heterosexual male 79X for MSM 1 in 6 (17%) vs 1 in 473 (0.2%) Lifetime risk may be a useful tool to more effectively communicate the risk of HIV to the general public and can help to highlight severe disparities Hess K. et al. CROI Boston, MA. Oral 52 4

5 One-In-Statement for Adults (age 13+) 1 in 152 adult Floridians are known to be currently living with HIV infection. 1 in 299 whites are currently living with HIV infection 1 in 48 blacks are currently living with HIV infection 1 in 160 Hispanics are currently living with HIV infection Data as of 06/30/2016 5

6 The Epidemic in Florida Population Trend 19.6 million (57% White, 15% Black, 24% Hispanic, 4% Other) 19.8 million (56% White, 16% Black, 24% Hispanic, 4% Other) 1.02% increase Newly Diagnosed HIV cases 4,600 4, % increase Newly Diagnosed AIDS cases 2,291 2, % decrease People diagnosed & living with HIV 110,000 (30% White, 47% Black, 21% Hispanic, 2% Other) 112,000 (29% White, 47% Black, 22% Hispanic, 2% Other) 1.82% increase Pediatric AIDS cases diagnosed % decrease HIV prevalence estimate 126,100 (12.8% unaware of status) 127,900 (12.4% unaware of status) 1.43% increase HIV-related deaths % decrease 6

7 3,500 MSM IDU MSM/IDU Heterosexual Number of Cases 3,000 2,500 2,000 1,500 1, Year of Diagnosis Note: Male-to-male sexual contact (MSM) remains as the primary mode of exposure among male HIV cases in Florida, followed by heterosexual contact 7

8 Persons Living with HIV Disease, by County of Residence,* Diagnosed through 2014, Florida Living Case Counts N=109,969 1 to to 1,000 1,001 to 1,500 > 1, *County totals exclude Department of Corrections cases (N=4,085). Numbers on counties are cases reported. Data as of 06/30/

9 Florida STI Epidemic

10 Syphilis 1 and HIV Cases Diagnosed ,000 Syphilis HIV Number of Cases 6,000 5,000 4,000 3,000 2,000 1, Year of Diagnosis 1 Syphilis data include both Primary and Secondary Syphilis. Source: STD data were validated through Florida CHARTS as of 06/27/

11 Chlamydia and Gonorrhea Cases Diagnosed Number of Cases 100,000 90,000 80,000 70,000 60,000 50,000 40,000 30,000 20,000 10,000 0 Chlamydia Gonorrhea Year of Diagnosis Source: STD data were validated through Florida CHARTS as of 06/27/

12 Florida s Plan to Eliminate HIV Transmission and Reduce HIV-related Deaths Four Key Components 1. Test and treat and retain in care 2. Antiretroviral pre-exposure prophylaxis (PrEP) and non-occupational post-exposure prophylaxis (npep) 3. Routine HIV and Sexually Transmitted Infection (STI) screening in healthcare settings/targeted testing in non-health care settings 4. Community outreach and messaging 12

13 Pre-exposure Prophylaxis (PrEP) 13

14 What is PrEP? PrEP stands for Pre-Exposure Prophylaxis. PrEP is intended to prevent a person from becoming HIV infected if exposure to the virus occurs

15 Antiretrovirals Used in HIV Prevention: The Foundation for PrEP Prevention of mother-to-child transmission (PMTCT) 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 Non-human primate studies demonstrating protection [2,3] Observational data [4] 1. DHHS. Perinatal Guidelines Am. J Med. 1997;102(5B): J Virol. 1998;72(5): NEJM. 1997;337(21): Modified from Clinical Care Options: clinicaloptions.com/hiv 15

16 Clinical Trial Evidence for HIV Prevention Options (February 2016) Prevention of sexual transmission PROUD daily oral TDF/FTC (MSM United Kingdom) IPERGAY event-driven TDF/FTC (MSM Canada, France) Partners PrEP daily oral TDF/FTC (Serodiscordant couples Kenya, Uganda) Partners PrEP daily oral TDF (Serodiscordant couples Kenya, Uganda) TDF2 daily TDF/FTC (Heterosexual men and women Botswana) iprex daily oral TDF/FTC (MSM North and South America, South Africa, Thailand) Effect size (CI) 86% (58; 97) 86% (44; 99) 75% (55; 87) 67% (44; 81) 62% (22; 84) 44% (15; 63) CAPRISA 004 BAT-24 dosing vaginal tenofovir gel (Women South Africa) RV 144 six injectable ALVAC/AIDSVAX (Heterosexual men and women Thailand) The Ring Study monthly vaginal ring containing dapivirine (Women South Africa, Uganda) ASPIRE monthly vaginal ring containing dapivirine (Women Malawi, South Africa, Uganda, Zimbabwe) MTN 003/VOICE daily dosing vaginal tenofovir gel (Women South Africa, Uganda, Zimbabwe) FEM-PrEP daily oral TDF/FTC (Women Kenya, South Africa, Tanzania) FACTS 001 event-driven vaginal tenofovir gel (Women South Africa) MTN 003/VOICE daily oral TDF/FTC (Women South Africa, Uganda, Zimbabwe) MTN 003/VOICE daily oral TDF (Women South Africa, Uganda, Zimbabwe) R R R 39% (6; 60) 31% (1; 51) 31% (1; 51) 27% (1; 46) 15% (-21; 40) 6% (-21; 40) 0% (-40; 30) -4% (-49; 27) -49% (-129; 3) Prevention in people who inject drugs DELIVERY SYSTEM Bangkok Tenofovir Study daily oral TDF (PWID Thailand) ACTIVE DRUG % (10; 72) Vaccine Vaginal gel Oral pills Vaginal ring ALVAC/AIDSVAX Tenofovir Tenofovir/ emtricitabine (TDF/FTC) Dapivirin e Tenofovir disoproxil fumarate (TDF) Effectiveness (%) Adapted from: Salim S. Abdool Karim, CAPRISA 16

17 Four Scenarios of the Potential Impact of Expanded HIV Testing,Treatment and PrEP in the United States, New Infections HIV Infections prevented due to expanded testing and treatment HIV Infections prevents due to PrEP (assumes PrEP use among high=risk populations = 40% MSM; 10% PWID; 10% HET) Total number of new HIV infections 2015 through , , , , ,000 50, ,330 48, ,109 31,988 88, ,434 16, ,132 80,270 Scenario 1 Scenario 2 Scenario 3 Scenario 4 Projected new infections by 2020 at current testing and treatment rates If PrEP uses increases among high-risk populations at current testing and treatment rates Infections prevented through PrEP If 85% of people diagnosed are linked to care, 60% achieve viral suppression, plus PrEP use Infections prevented through PrEP Infections prevents through testing and treatment Infections prevented through PrEP Achieving NHAS goals if 85% of people diagnosed are linked to care, 80% achieve viral suppression, plus PrEP use Infections prevents through testing and treatment Source: Centers for Disease Control and Prevention 17

18 Four Scenarios of the Potential Impact of Expanded HIV Testing, Treatment and PrEP in the Florida, New Infections HIV Infections prevented due to expanded testing and treatment HIV Infections prevents due to PrEP (assumes PrEP use among high=risk populations = 40% MSM; 10% PWID; 10% HET) Total number of new HIV infections 2015 through ,000 25,000 20,000 15,000 10,000 5, ,475 4,992 22,483 3,313 9,207 14,955 1,753 17,410 8,312 Scenario 1 Scenario 2 Scenario 3 Scenario 4 Projected new infections by 2020 at current testing and treatment rates If PrEP uses increases among high-risk populations at current testing and treatment rates Infections prevented through PrEP If 85% of people diagnosed are linked to care, 60% achieve viral suppression, plus PrEP use Infections prevented through PrEP Infections prevents through testing and treatment Achieving NHAS goals if 85% of people diagnosed are linked to care, 80% achieve viral suppression, plus PrEP use Infections prevented through PrEP Infections prevents through testing and treatment Source: Florida Department of Health 18

19 PrEP Key Points Truvada (TDF/FTC) is a combination of nucleoside reverse transcriptase inhibitors (NRTIs) tenofovir disoproxil fumarate 300 mg (TDF) & emtricitabine 200 mg (FTC). FDA approved TDF/FTC works by inhibiting HIV from replicating when it enters the body. This keeps HIV from establishing itself in the body permanently. Image credit: 19

20 PrEP Key Points (continued) TDF/FTC for PrEP is one component of a comprehensive prevention strategy that includes safer sex practices, Sexually Transmitted Disease (STD) screening and motivational interviewing directed at behavioral change. 20

21 Who Should Be Offered PrEP?: CDC Guidelines Substantial risk of HIV Infection Men Who Have Sex with Men Heterosexual Women and Men Injection Drug Users HIV-positive sexual partner Recent bacterial STI HIV-positive sexual partner Recent bacterial STI HIV-positive injecting partner Sharing injection equipment Recent drug treatment (but currently injecting) High number of sex partners History of inconsistent or no condom use Commercial sex work High number of sex partners History of inconsistent or no condom use Commercial sex work Center for Disease Control and Prevention Guidelines

22 Clinical Assessment for PrEP Use Clinically eligible Prescription Other Services STI: sexually transmitted infection Men Who Have Sex with Men Heterosexual Women and Men Injection Drug Users Documented negative HIV test result before prescribing PrEP No signs/symptoms of acute HIV infection Normal renal function; no contraindicated medications Documented hepatitis B virus infection and vaccination status Daily, continuing, oral doses of TDF/FTC (Truvada ), 90-day supply Follow up visits at least every 3 months to provide the following: HIV test, medication adherence counseling, behavioral risk reduction support, side effect assessment, STI symptom assessment Do oral/rectal STI testing At 3 months and every 6 months thereafter, assess renal function Every 6 months, test for bacterial STIs Assess pregnancy intent Pregnancy test every 3 months Access to clean needles/syringes and drug treatment services 22

23 Considerations When Prescribing Counsel patients on the importance of adherence to the prescribed medication regimen. TDF/FTC effectiveness is strongly correlated with consistent adherence 7 days for protective TDF/FTC drug levels for receptive anal sex & 20 days for blood, vaginal sex and insertive anal sex Nausea, vomiting, stomach pain, diarrhea, headache, dizziness, depression, joint pain Modified from 23

24 Considerations When Prescribing (continued) A negative HIV test must be confirmed immediately before starting a regimen of TDF/FTC HIV screenings should be repeated every three months along with STI and adherence assessments and counseling for behavior change If symptoms of acute HIV infection occur, discontinue TDF/FTC until negative status can be confirmed 24

25 Acute HIV Infection Signs/symptoms of acute HIV infection include: [2016 CDC npep update] Fever (75%) Fatigue (68%) Myalgia (49%) Skin rash (48%) Headache (45%) Pharyngitis (40%) Cervical adenopathy (39%) Arthralgia (30%) Night sweats (28%) Diarrhea (27%)

26 Acute HIV Infection (continued) If a patient becomes HIV positive while on PrEP, then they may discontinue PrEP. HIV-infected patients must take TDF/FTC with other antiretroviral medications (ARVs) to fully suppress the HIV virus and prevent resistance. 26

27 Warnings, Precautions, and Adverse Events Renal Impairment Do not administer TDF/FTC with or following recent use of nephrotoxic drugs Offer alternatives to NSAIDS for patients with renal impairment Discontinue use if CrCl < 60 ml/min 27

28 Warnings, Precautions, and Adverse Events (continued) Adverse Reactions reported by >2% of patients during clinical trials: Headache Abdominal pain Weight loss Hepatitis B All patients should be tested for chronic HBV before beginning TDF/FTC 28

29 TDF/FTC as PrEP in Specific Populations Pregnant Women While there have been no well-controlled trials of the use of TDF/FTC during pregnancy, it should be used only if a need is clearly indicated. A pregnancy registry is available for pregnant women on TDF/FTC for PrEP: call

30 Truvada as PrEP in Specific Populations (continued) Breastfeeding Women The components of TDF/FTC are excreted in breastmilk Risk to the infant is unknown at this time; therefore, women on TDF/FTC should not breastfeed. 30

31 Reducing Risk of HIV Acquisition Safer sex/needle practices Knowledge of their own HIV status as well as the status of their partner(s) Regular HIV testing of self and partner(s) Medication compliance Adherence Benefits of Adherence Decreased Risk of HIV Transmission

32 TDF/FTC: STI PrEP Demo Project, SF Cohen CROI 2016 #870 Sep 2012-Jan men and women with quarterly screening 51% had an STI during f/u 20-41% of STI missed with q6 mo screening Conclusion: quarterly screening 32

33 PrEP A Cautionary Tale 43 year old man from Toronto On TDF/FTC PrEP X 24 months (+pharmacy records, dried blood spots with TFV-DP ~2300 fmol/punch) Found p24 Ag+, HIV antibody (-), HIV RNA ~28K Knox CROI 2016 #169aLB 33

34 PrEP A Cautionary Tale (continued) Drug resistant virus NRTI: 41L, 67G, 69D, 70R, 184V, 215E NNRTI: 181C II: 51Y, 92Q; phenotypic resistance to all II Phylogenetic analysis: narrow range Conclusion: PrEP failure with MDR 34

35 Case Report: Wild-Type HIV-1 Infection in MSM Adherent to PrEP 50-yr-old MSM using daily oral FTC/TDF PrEP in Amsterdam Pre-Exposure Prophylaxis project Reported drug use during sex, excellent PrEP adherence Median number of condomless anal sex partners per day in each month following PrEP initiation ranged from 2-5 Tested positive for rectal STIs - gonorrhea (2x) and chlamydia HIV Ag/Ab results negative at PrEP start and after 1, 3, 6 months After 8 months: fever, dysuria, HIV Ab positive, Ag negative, and HIV-1 RNA negative; PrEP discontinued and HIV- 1 RNA detectable 3 weeks later; no drug resistance detected Dried blood spot TFV-DP levels protective at months 6 and 8 HIV-1 RNA suppressed 1 months after initiating ART Hoornenborg E, et al. CROI Abstract 953. Slide credit: clinicaloptions.com 35

36 Wild-Type HIV Infection While Adherent to PrEP First reported case of WT HIV infection in person with protective TFV-DP levels Seroconversion pattern atypical: no HIV DNA in bulk PBMCs, no HIV DNA or RNA in 3 sigmoid biopsies at time of seroconversion Hypothetical mechanisms of infection High number of repeated HIV exposures with or without mucosal damage? Decreased TDF and/or FTC levels in rectal mucosa? Highlights importance of periodic HIV testing during PrEP use and awareness of potential for atypical seroconversion patterns Hoornenborg E, et al. CROI Abstract 953. Slide credit: clinicaloptions.com 36

37 PrEP TDF/FTC versus TAF/FTC TAF/FTC protects monkeys 1 Tenofovir levels in human tissue comparing TAF to TDF 2 cervical and vaginal tissue levels 2-fold lower with TAF rectal tissue levels 10-fold lower with TAF 1 Massud I et.al.,croi 2016, Boston, Abstract Garrett KL, et.al.; CROI 2016, Boston, Abstract 102LB 37

38 Medical Team s PrEP Resources 38

39 Southeast AIDS Education & Training Center (SEAETC) POCKET GUIDE FOR PEP, PREP AND npep The Southeast AIDS Education and Training Center brochure is available from their website or downloaded in PDF form. The pocket guide expands on PrEP, PEP, and npep. 39

40 PrEP and npep Help Lines (continued) For PrEP advice and inquiries, please call the PrEP line: (855) or (855) HIV-PrEP Monday through Friday, 11 a.m. 6 p.m. EST Provides free, expert advice about PrEP to clinicians across the country. 40

41 PrEP and npep Help Lines Clinician Consultation Center For all patient-specific PEP inquiries, call the PEP phone consultation line: (888) a.m. 2 a.m. EST, seven days a week 41

42 Non-occupational Post-exposure Prophylaxis (npep) 42

43 What is npep? Non-occupational post-exposure prophylaxis (npep) is prescribed to prevent HIV infection when administered no later than 72 hours following an exposure. npep may be given to: Anyone who has had unprotected sex (receptive vaginal or anal intercourse) Someone who has shared an injection needle with someone else who may have HIV Anyone who is a victim of sexual assault Modified from

44 Identifying Individuals at Risk Lower Risk Exposures Case by case evaluation if: Oral-vaginal contact Oral-anal contact Receptive penile-oral contact with or without ejaculation Insertive penile-oral contact with or without ejaculation 44

45 Identifying Individuals at Risk (continued) Higher Risk Exposures npep should be recommended for: Receptive and insertive vaginal or anal intercourse Needle sharing Injuries with exposure to blood or other potentially infected fluids from a source known to be HIVinfected or HIV status is unknown (sticks with hollowbore needle, human bites, accidents) 45

46 Identifying Individuals at Risk (continued) Risk increased if: Source person HIV positive with high viral load Non-intact oral mucosa Exposure to blood Presence of genital ulcer disease or other STD 46

47 Estimated per act risk for acquiring HIV from an infected source Exposure type Rate for HIV acquisition per 10,000 exposures Receptive Anal 138 Receptive penile-vaginal intercourse 8 Insertive anal intercourse 11 Insertive penile-vaginal intercourse 4 Receptive oral intercourse Low Insertive oral intercourse Low 2016 npep Guidelines update; CDC 47

48 Preferred HIV npep Regimen Recommended Regimen for HIV npep Tenofovir 300 mg + Emtricitabine 200 mg (coformulated as Truvada ) taken once daily PLUS Raltegravir (Isentress ) 400 mg PO twice daily or Isentress HD two 600 mg tablets once daily. Both taken with or without food OR Dolutegravir (Tivicay ) 50 mg PO taken once daily taken with or without food Alternative: TDF/FTC + darunavir (800mg) + RTV 100 mg taken once daily. CrCl < 60 ml/min use AZT + 3TC dose adjusted for renal insufficiency in place of TDF/FTC Source: 48

49 Considerations for All Patients Treated with npep Use starter packs (if available) Clinicians not experienced using ART should consult with HIV-care specialist Facilitate adherence Monitor for signs and symptoms associated with acute infection AIDS.2014;28(11): Mayer, et.al. Practical Guidance for npep to prevent HIV Infection. 49

50 npep follow-up: Exposed Person Baseline Wk 1 Wk 2 Wk 3 Wk 4-6 Wk 12 Clinic Visit (or call) (or call) (or call) (or call) Pregnancy Test LFT, BUN, Creat, CBC HIV Ag/Ab Test * STD Screen * If acute HCV infection acquired during original exposure repeat at 6 months ** If exposed person susceptible to hepatitis B and or C at baseline, repeat testing at 6 months. Hep B & C ** 50

51 Considerations for All Patients Treated with npep Proactively plan for management and medication access HIV PCR/RNA viral load testing if signs/symptoms of acute HIV infection occur Supportive monitoring for compliance with treatment and manage side effects HIV prevention counseling Consider and evaluate for PrEP 51

52 Patient Assistance for npep Truvada (tenofovir + emtricitabine): Gilead s Advancing Access Program Isentress (raltegravir): Merck s SUPPORT Program Tivicay (dolutegravir): ViiV Patient Assistance Program Source: 52

53 Patient Assistance for npep: When the Patient has Insurance Patient Advocate Foundation (PAF) Co-Pay Relief: If the patient has health insurance and the insurance covers medications for which patient needs assistance PAF CareLine Gilead s Co-Pay Coupon Program: If the patient has commercial insurance, he/she may contact or be referred to Gilead s Co-Pay Coupon Program The patient is given an authorization number to present with the prescription and other insurance at the pharmacy. 53

54 Additional Resources: PrEP and npep 54

55 Common ICD-10 Billing Codes: PrEP and PEP Z72.5 High-risk sexual behavior Z20.82 Contact with and (suspected) exposure to other viral communicable diseases W46.0 Contact with hypodermic needle (hypodermic needle stick NOS) Z51.81 Therapeutic drug level monitoring B20 Human immunodeficiency virus (HIV) disease. Includes: AIDS, AIDSrelated complex (ARC); HIV infection, symptomatic For additional information about ICD-10 coding, as well as access to additional HIV ICD-10 codes, visit: 55

56 Additional npep Resources Post-Exposure Prophylaxis (PEP) Hotline National HIV/AIDS Clinicians Consultation Center (NCCC): Call for a Phone Consultation (888) a.m. 2 a.m. EST, Seven days a week Florida/Caribbean AIDS Education & Training Center (F/C AETC) PrEP, npep, and opep Resource Update: HIV Prophylaxis Following Non-Occupational Exposure Updated October 2014 CDC: ARV PEP After Sexual, IDU, or Other Nonoccupational Exposure to HIV in the US,

57 Medical Team s npep Resources 57

58 Florida Department of Health: HIV/AIDS Medical Section Contact: Debra Taylor, RN, MPA, ASQ-CQIA Ext Dominic Matthews, RN Ext Roselyn Jasmin, Admin. Asst. Ext Jeffrey Beal, MD, AAHIVS Cell: