STIs and HIV Prevention for Men Who Have Sex with Men. Disclosures. Learning Objectives

Transcription

1 STIs and HIV Prevention for Men Who Have Sex with Men Ellen K. Opie, RN, FNP, MPH Nurse Practitioner, City Clinic San Francisco Department of Public Health With assistance from, and credit to our Medical Director, Stephanie Cohen, MD Disclosures The views expressed herein do not necessarily reflect the official policies of the City and County of San Francisco; nor does mention of the San Francisco Department of Public Health imply its endorsement. Gilead donated study drug for the PrEP Demo project, but was not involved in study design or data analysis Learning Objectives Understand STI screening recommendations for men who have sex with men (MSM) Be able to evaluate and manage common STI syndromes in MSM Identify potential candidates for pre-exposure prophylaxis. Name the tests that should be performed prior to initiating someone on PrEP

2 Case 1 At a new patient s initial visit, you learn he is a gay man who has had 3 sex partners in the last year. He feels fine and says all STD tests were negative a year ago. In addition to an HIV test, what else would you order? 1. No additional tests he is asymptomatic 2. Urine gonorrhea (GC) and chlamydia (CT) 3. Syphilis serology and Urine GC and CT 4. Pharyngeal GC, Rectal GC and CT, Urine GC and CT, syphilis serology 5. I need to know more before deciding STD Asymptomatic Screening for MSM Screen at least annually, or every 3-6 mos if high risk* HIV Syphilis Urethral GC and CT Rectal GC and CT (if anal sex) Pharyngeal GC (if oral sex) Also screen for: Hepatitis B surface Ag (frequency not specified) Hepatitis C if IDU, born or transfusion before 1992 * High risk: multiple and/or anonymous partners, drug use, or these risks in patient s partners CDC 2015 STD Tx Guidelines Proportion of asymptomatic rectal and urethral chlamydial and gonococcal infection among MSM San Francisco City Clinic, 2011 Rectal Infections Urethral Infections Chlamydia n=308 Gonorrhea N=237 Asymptomatic Symptomatic Adapted from Kent, CK et al, Clin Infect Dis July 2005 Chlamydia n=234 Gonorrhea n=244

3 Proportion of Chlamydia or Gonorrhea infections in asymptomatic MSM MISSED if only urine screened n=3398 Chlamydia Gonorrhea Marcus et al, STD Oct 2011; 38: Slide Courtesy I. Park MD, MS Case 1, continued Patient reports receptive and insertive anal sex (intermittent condom use) and oral sex. The rectal NAAT is positive for Chlamydia. His other NAATs, syphilis test and HIV Ab test are all negative. What treatment would you recommend? 1. Azithromycin 1 g PO x 1 2. Levofloxacin 250 mg PO x 1 3. Ceftriaxone 250 mg IM x1 PLUS azithromycin 1 PO x1 4. Doxycycline 100 mg PO BID x 7 days 5. 1 or , 3 or 4 Chlamydia Treatment: Areas of Clinical Uncertainty Observational data suggest azithromycin may be less effective than doxycycline for anorectal Chlamydia infection Four published studies, 2 abstracts Not randomized Most single arm or historical cohort as comparator Varying times to test of cure Low rates of follow-up

4 Rectal Chlamydia No changes to guidelines proposed based on these data Need RCT Some sites using doxycycline as 1 st line treatment for rectal CT Case 2 Your patient is asymptomatic and you treat him with azithromycin 1 g PO once. Six months later, he returns reporting rectal discharge and pain with sex. His exam is notable for perianal ulcerations, hemorrhoid-like masses and bloody, purulent discharge on anoscopy. Microbiologic Etiology of Proctitis SFCC, (n=1246) 14.53% Rectal GC Only Rectal CT Only Cohen, ISSTDR % 10.91% 3.29% 7.46% 1.20% 3.05% Rectal GC and CT HSV Only Syphilis Only Other multiple diagnoses

5 Case 2, Continued You test himagain for HIV and STDs You treat him with Ceftriaxone 250 mg IM x1, plus Doxycycline 100 mg PO BID and Acyclovir 400 mg PO BID x 7 days for proctitis His rectal CT NAAT is positive HIV Ab, RPR, rectal GC NAAT and HSV PCR are negative Case 2: What would you do? 1) Obtain a repeat STD/HIV screen (including rectal GC/CT NAAT) in 3 months 2) Ask him to return for CT test of cure in 3 weeks 3) Order a test for LGV 4) Presumptively extend his doxycyclinecourse from 7 days to 21 days Lymphogranuloma Venereum (LGV) Caused by CT serovarsl1, L2 or L3 Primary lesion is a small, genital papule that can ulcerate 2 main syndromes: Tender, fluctuant lymphadenopathy ( bubo ) Hemorrhagic proctitis or proctocolitis 5-30% symptomatic rectal CT is LGV Treat: Doxycycline x 3 weeks Associated with HIV and HCV transmission

6 Proctitis Recommended Treatment: Ceftriaxone 250 mg IM once, PLUS Doxycycline 100 mg orally BID x 7 days PlusHSV coverage if ulcers are present If LGV suspected: Doxycycline 100 mg orally BID x 3 weeks Presumptive treatment of LGV for MSM with proctitis and anorectal chlamydia, particularly if the patient is HIV-infected or any of the following symptoms or signs are present: bloody discharge, perianal ulcers or mucosal ulcers ElgalibA, IntJ STD AIDS 2011; HathornE, STI 2012, Hill IntJ STD AIDS 2010, de VriezeSTI Case 2, Continued You counsel your patient about proctitis, discuss how to ensure his partners are treated & ask him about his condom use practices. He tells you that he uses condoms with new partners if he does not know their HIV status and asks you if you will prescribe him PrEP. What would you do? 1) Refer him to an HIV/ID specialist 2) Encourage him to use condoms with all of his partners because that is more effective than PrEP 3) Order a HIV antibody, creatinine and Hepatitis B test and ask him to come back in two weeks 4) Order HIV antibody, creatinine and Hepatitis B test & write him a prescription for 30 days of Truvada 300/200mg (FTC/TDF) 5) Call the CDC PrEP warmline 6) Open uptodate Question A patient has asked me about PrEP. 1) YES 2) NO

7 Question I have prescribed PrEPto a patient. 1) YES 2) NO Why are New HIV Prevention Tools Needed? Despite testing, counseling, condoms, and ART, 40,000-50,000 new infections annually in the U.S. Incidence far higher in Sub-Saharan Africa, Eastern Europe, Southeast Asia, and in certain populations Men who have sex with men (MSM) Racial and ethnic minorities Injection drug users (IDU) GOOD NEWS 33% decrease in annual diagnoses BAD NEWS MSM years old Black Women 500,000 infections % of new diagnoses in men < 25 years of age Especially, young MSM of color CDC fact sheet; Johnson et al, JAMA 2014.

8 Current HIV Prevention Methods: where are the gaps? Method (+) (-) Testing/Counseling + Condoms ART as Prevention ( TasP ) PEP (Post-exposure Prophylaxis) SEROSORTING Positive: HIV+ only have condomless anal sex w other HIV+ Negative: perceived HIV-only -Knowledge of HIV +status leads to decrease in risk behavior -Counseling:individual benefits? -Condoms:67%-80% efficacy if used correctly, consistently 96% risk reduction in serodiscordantheterosexual couples (HPTN052) 80% risk reduction (AZT monotherapyin occupational exposure) - Positive serosorting: limits HIV transmission if both partners truly HIV+ - Negative serosorting: Better than nothing? Maybe? Condomefficacy drops off quickly if not used correctly, consistently Inconsistentuse no more efficacious than nonuse in recent CDC modeling study; 16% consistent use in US MSM -Does not protect partners of infected-unknowns (esp. AHI) -requires higher testing, linkage, retention than current rates -intermittent viremia? - fewer data for MSM -underutilized -requiresinitiation within 72h of recognized risk Depends on: - Bothpartners accurate understanding of status - Frequent testing of HIV- -No recent exposure since last What ispre-exposure Prophylaxis? FDA approved emtricitabine/tenofovir (FTC/TDF, or Truvada ) 16 July 2012 for use as PrEP in combination with safer sex practices to reduce the risk of sexually-acquired HIV infection in adults at elevated risk Taken daily regardless of plans for sex As part of a comprehensive HIV prevention plan PLUS regular monitoring for HIV infection, STIs, drug safety, adherence Pre-Exposure Prophylaxis Provides a partner-independent prevention method totally controlled by the user independent of the state of mind immediately prior to and during sex Fills gaps in current prevention methods

9 PrEP and the test/treat model I. Universal, accessible HIV/STD testing -Frequency determined by risk -Testing for acute infection in high-risk populations/settings IF (-) III. COMBINATION PREVENTION Condoms and Risk Reduction coaching Referrals for Substance use treatment, Mental health care PEP for occasional exposures PrEP for Pts with elevated risk: Inconsistent condom use Multiple partners/non-monogamous steady partnerships Serodiscordantpartners including periconception h/o Rectal STIs, PEP IF(+) II. IMMEDIATE ART Eliminate OIs/AIDS nonaids complications transmission to partners Does PrEP Work? Efficacy Results from Randomized Controlled Trials (RCT) A Rapidly Evolving Field iprex Partners PrEP, TDF2, Fem-PrEP Bangkok IDU PROUD, IPERGAY, Demo VOICE New drugs Different delivery Long acting

10 TRIAL POPULATION LOCATION Active arm(s) EFFICACY iprex 2499 MSM and MTF SouthAmerica, USA, FTC/TDF 44% (95% CI 18-60) Thailand, South 48 FTC/TDF vs. 83 placebo Africa TDF heterosexualmen Botswana FTC/TDF 63% (95% CI 22-83) and women 9 FTDC/TDF vs. 24 placebo Partners 4758 serodiscordant Kenya and Uganda FTC/TDF 75% (95% CI 55-87) PrEP heterosexualcouples TDF 67% (95% CI 44-81) 13 FTC/TDF, 17 TDF, 52 placebo FEM-PrEP 2120 heterosexual women Kenya, Tanzania, Zimbabwe, South Africa FTC/TDF No difference 33 FTC/TDF vs. 35 placebo Stopped early due to lack of efficacy VOICE 5000 heterosexual women Uganda, Zimbabwe, South Africa FTC/TDF TDF Vaginal TDF gel NoDifference Bangkok IDU 2413 IDU Bangkok TDF DOTormonthly visits, by choice 48.9% (95%CI , P=0.01) PROUD 545 MSM Q3m visits Public GUD clinics in UK Immediate vs deferred (12m) FTC/TDF 86% (90%CI 58-96, P=0.0002) 3 immediate arm, 19 deferred NNT=13 IPERGAY 400 MSM Q2m visits France, Quebec Pre/post sex FTC/TDF vs placebo 86% (95%CI 40-99) 2FTC/TDF, 14 placebo NNT=18 PrEP Efficacy PrEP works extremely well IF you take it PrEP Efficacy and Drug Detection Study Efficacyoverall Drug detected overall Risk reductionwith drug detection iprex 42% 50% 92% Partners PrEP 67%(TDF) 75% (FTC/TDF) 82% 86%(TDF) 90% (FTC/TDF) TDF-2 62% 80% 78% Fem-PrEP VOICE Stopped early due to futility Stopped early due to futility < 40% adherence too low to assess efficacy < 30 % adherence too low to assess efficacy BangkokIDU 49% 66% 74%

11 DOES ADHERENCE HAVE TO BE PERFECT? Dosing Estimated PrEPEfficacy 2x/week 76% NO infections seen w/ 4 doses/week 4x/week 96% Daily 99% Anderson PL. SciTranslMed 2012;4:1-8. Grant RM, Anderson PL et al. Lancet InfDis PrEP Efficacy in real world studies US PrEP demonstration project 3 participants acutely infected at enrollment 2 seroconversions: 0.43/100 PYs (95% CI ) But at least 2 additional seroconversions post study in participants who did not continue PrEP SF Kaiser PrEPprogram Zero HIV seroconversions after 388 PYs of follow-up Liu JAMA Intern Med 2016; Volk CID 2015 Summary of PrEP RCTs PrEP found to be moderately to highly efficacious in MSM, MSW, IDU Highly efficacious in those who take it consistently Adherence is the key variable: doesn t have to be PERFECT, but has to be better than good (for rectal sex) Efficacy results in women mixed Adherence is a major factor Differential cervicovaginal vs rectal tissue penetration?? 20 days to maximal cervicovaginal levels? Do women need to be moreadherent than men? CDC. MMWR MorbMortal Wkly Rep. 2011;60: Grant RM. N EnglJ Med. 2010;363: BaetenJ. Annu. Rev. Med :

12 How do I prescribe PrEPin primary care? 1) Take a sexual history (The 5 P s) Partners Prevention of Pregnancy Protection from STDs Practices Past history of STDs How do I prescribe PrEP in primary care? 2) Identify patients who may benefit from PrEP CDC guidelines: Sexually-active MSM, heterosexual men and women & IDU at substantial risk MSM or transgender women -condomlessanal intercourse with multiple partners MSM or transgender women - syphilis or rectal STI Commercial sex workers Men or women in serodiscordantrelationships with positive partners with detectable viral load Peri-conception Prior STD places men at risk for HIV 10% 8% 7.9% Annual HIV Incidence 6% 4% 2% 5.6% 0% MSM with syphilis Men with syphilis and subsequent NG/CT/LGV Pathela CID 2015

13 3) Discuss PrEP with your patient What is the patient currently doing to protect himself from HIV? Discuss condom use, role of substance use, risk perception, prevention goals Key counseling points: Daily dosing Important to get tested for HIV regularly (at least every 3 months) while taking PrEP Anticipatory guidance re start-up syndrome Discussion of how to stop and safely re-start PrEP Additional resources for talking to your patient about PrEP

14 4) Take a Medical History and do a Symptom Review Osteoporosis and liver disease are relative contraindications to TDF/FTC Moderate kidney dysfunction is an absolute contraindication Patients with recent symptoms of a mono-like illness should be tested for acute HIV. Wait to start PrEPuntil test results are back 5) Obtain Baseline Testing HIV Antibody test (rapid if available). Strongly suggest obtaining a viral HIV test for acute HIV when PrEP initiated. Creatinine(CrCl should be 60 ml/min) HBsAg STDs Pregnancy test Offer Hep B immunization if not immune Offer HPV immunization if <26 6) Discuss how patient will pay for Truvada Coverage How toaccess Uninsuredand < 500% FPL Gileadpatient assistance program (PAP) provides TDF/FTC 300/200mg at no cost Client may need to pay for office visit and labs Uninsured and > 500% FPL Payout of pocket ($1250/month) + office visits, lab costs Medical Covered; No prior authorization in California Employer-sponsoredhealth insurance In general, most plans cover TDF/FTC for PrEP Cost sharing varies; Gilead offers co-pay assistance Some require prior authorization, mail order Rx Provider needs to code visit correctly or q3mo HIV testing may not be covered Covered California Bronze: High deductible, 30-40% co-insuranceafter deductible met; TDF/FTC approx $800/mo (with co-pay assistance) Silver, Gold: Most have no cost after co-pay card

15 7) Counseling Risk reduction Sexual and drug using behaviors and current efforts for remaining HIV negative How PrEP fits in with overall sexual health goals/plan Adherence PrEP basics handout (at PrEP initiation) Discuss pill-taking experience Facilitators/barriers Strategies 8) Ongoing Monitoring and Support Timeframe Action 30 days after initiation Assess side effects and the patient s interest in continuing Adherence counseling: reinforce importance of daily use and address any challenges patient has faced. Every 3 months HIV test: 4 th generation preferred If the patient has been off PrEP for more than a week, consider screening for acute HIV at time of PrEP re-initiation Creatinine: stop if CrCl < 60 ml/min STD screening Pregnancy test for women; If pregnant, ensure that the patient has been informed about use during pregnancy and that she discusses PrEP use with her prenatal provider. Renew prescription for 90 days only if HIV test negative At visit: adherence and risk reduction counseling 9) What if my patient has a positive HIV test? Discontinue PrEP to avoid development of resistance Order and document results of an HIV genotype Ensure patient is linked to an HIV-primary care provider for care and possible early initiation of ART Inform health dept

16 SFDPH PrEP Navigation Services Take Home Screen sexually active MSM for STDs, including extragenitalgc and CT (throat, rectal) PrEP highly effective in preventing HIV acquisition, dependent on adherence PrEP safe and well tolerated Recommend PrEP for those at elevated risk for HIV Baseline and at least q3month HIV testing critical component of PrEP delivery Stephanie Cohen Al Liu Oliver Bacon Jonathan Volk Susan Buchbinder Bob Grant Susan Philip Ina Park Joseph Engelman Acknowledgements

17 Extra slides PrEP and Risk Compensation in the Real World % DBS 4 doses/week and reporting CRAS Adherence, Risk Behavior, and STI incidence Over Time in the Demo Project Visit week STI incidence, per 100 py Liu et al. IAS 2015 DBS levels 4 doses/week (%) Reported CRAS (%) STI incidence (per 100 py) Lower/Upper 95% CI for STI incidence Volk et al. CID HIV uninfected MSM on PrEP at SF Kaiser 2 incident HCV infections 0 HIV infections

18 PrEP in Clinical Practice: What Are the Barriers to PrEP Uptake? Users Providers 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 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 Understanding PrEP Example: Birth Control Oral Contraceptive ( The Pill ) Prevents pregnancy if taken before sex. Does not work as morning-after pill. Does not always start working immediately. Must take daily cannot skip doses. Only helps prevent pregnancy, will not prevent STIs (should still use condoms). Very effective at preventing pregnancy, but not 100% effective. Should be taken by anyone who is sexually active (at risk for becoming pregnant) Pre-Exposure Prophylaxis (PrEP) Prevents HIV infection pre-exposure. Will not work if already exposed. Does not start working immediately. Must take daily cannot skip doses. Only helps prevent HIV will not prevent other STIs (should still use condoms). Very effective at preventing HIV infection, but not 100% effective. Should be taken by anyone who could be exposed to the HIV virus (at risk for HIV)

19 Common PrEP-Related Billing Codes ICD-9 Description V69.2 High-risksexual behavior V01.79 Exposureto other viral diseases V65.44 HIV Counseling ICD-10 Description Z72.5 High-risk sexual behavior Z20.82 Contact with and (suspected) exposure to other viral communicable diseases CPT Description Preventive counseling(15 min) Preventive counseling(30 min) Preventive counseling(45 min) Preventive counseling(60 min) CDC PrEP Guidelines 2014;