Sexually Transmitted Diseases (STDs) and HIV: Top Ten Highlights for Clinicians

1. Sexually Transmitted Diseases (STDs) and HIV: Top Ten Highlights for Clinicians Dana W. Dunne, MD, FACP Associate Professor of Medicine Yale University School of Medicine New Haven, Connecticut New York, New York: March 23, 2016 From DW Dunne, MD, FACP, at New York, NY: March 23, 2016, IAS-USA.

2. Why you should care? • HIV incidence rates remain high • STI- marker of high risk activity • STI- personal and public health concern • STI- enhance transmission of HIV • Getting to zero = more effective STI screening and treatment in our HIV-infected patients

3. Learning Objectives After attending this presentation, participants will be able to: • Identify elements and rationale of an effective STI screening approach • Recognize current STI epidemiology in HIV clinic and PrEPsetting • Describe recommended treatment and partner notification approaches for key bacterial STIs Outline-

4. Let’s take a trip to the clinic… You are seeing Mr. G.P. for a routine HIV clinic appointment. He has well controlled HIV; self-describes as bisexual currently with a stable female partner. You have clinical questions about the following: • Are STI rates really that high in HIV clinic to warrant testing after initial intake? • Can you limit STI screening to only sites exposed? • Can’t you pick up most things just by having him pee in a cup?

5. STI rates are high in HIV clinics • High baseline and incident STIs in HIV clinic US: HIV Primary Care clinic- 4 cities (n=557) • 13% prevalent STI, 7% incident STI • MSM- accounted for 94 % of infections (if trich excluded); 20% of incident STIs at 6 months • most common: rectal CT, pharyngeal GC • Risk factors – polysubstance abuse ; >4 partners in 6 months • Screening rates suboptimal • 39% of HIV patients screened for GC/CT (vs 76% lipid screening) • 10% Extragenital screening in MSM Mayer K, et al. STD 2012 Berry JAIDS, 2015

6. Tip #1- Remember routine STI Testing during HIV care Initial care visit • Syphilis serology • Gonorrhea, chlamydia NAAT (at sites exposed) • Women- • Trichomonas testing (NAAT, culture) • Cervical pap test per existing guidance (HIV OI guidelines) • Hepatitis A/B/C testing ##More frequent screening dependent on risk! • New sex partner, partner with concurrent partners or more than one partner, or partner with an STI High risk behavior Partner services, prevention counseling CDC 2015 Treatment Guidelines, HIVMA 2014

7. Tip # 2: Don’t rely on symptoms or self-reported exposure Selective or symptom screening can miss up to half of STIs- (Van Liere 2013) Screening only urine misses majority of STIs in MSM- (Marcus 2011) Proportions of chlamydial and gonococcal infections among asymptomatic men who have sex with men that would be missed by different screening practices—San Francisco City Clinic, 2008–2009.

8. Screening- What swab do I use? Genital Testing Extragenital Testing* Pharyngeal- Like strep throat swab Rectal- Provider or patient collected *check for lab validation locally • Men- • Urine = urethral swab • Women • Urine << Vaginal Swab; cervical • Vaginal- provider or patient collected

9. Tip #1 and 2- Universal screening every 3-6 months for at-risk patients • Regardless of symptoms • Regardless of site exposed • Can be pt collected Pharyngeal GC NAAT** Urine GC/CT NAAT Rectal GC/CT NAAT** *In HIV-coinfected individuals, screen hep C at least annually **Off-label use - not FDA-approved for testing at extragenital sites, but many reference labs have validated the assay for use

10. Your patient’s STI screen results return. He has pharyngeal gonorrhea but chlamydia testing from all sites (using NAATs) is negative. How to treat? • Ceftriaxone 125 mg IM x 1 • Ciprofloxacin 500 mg po x 1 plus azithromycin 1 gm po x 1 • Cefixime 400 mg po x 1 • Ceftriaxone 250 mg IM x 1 • Ceftriaxone 250 mg IM plus azithromycin 1 gm po x 1 1

11. Tip #3- Use DUAL Treatment for Gonorrhea Gonorrhea- Uncomplicated Genital, Rectal, or Pharyngeal Infections Ceftriaxone 250 mg IM in a single dose* Azithromycin 1 g orally PLUS* * Regardless of CT test result Azithromycin 2 g orally removed as an alternative regimen *If CTX unavailable-Cefixime 400 mg orally once (anorectal infection only) CDC 2015 STD Treatment Guidelines www.cdc.gov/std/treatment

12. Tip #4-Rescreen 3-4 months after STI Women with CT, GC or trichomonas should be rescreened at 3 months after treatment. Men with CT or GC should be rescreened at 3 months after treatment. Patients diagnosed with syphilis should undergo follow up serology per current recommendations.

13. You remember something about partner notification… Expedited Partner Therapy (EPT) is legal in my state: • Yes • No • I don’t know 1

14. Tip #5-EPT is effective and now legal in (most) all states Legal Status of EPT as of 2016 “PDPT can prevent reinfection of index case and has been associated with a higher likelihood of partner notification…” www.cdc.gov/STD/EPT

15. EPT – local details

16. Your patient tells his female partner about EPT but she prefers to come to the clinic. She is known to be HIV+. You commence routine STI screening and treat her as a contact to GC. Her Trichomonas antigen test returns positive. Which of the following is recommended for treatment? • Metronidazole gel 2% intravaginally q hs 5 nights • Metronidazole 2 gm orally x 1 dose • Metronidazole 500 mg orally BID x 7 days • No treatment necessary as she is asymptomatic and not pregnant 1

17. Trichomonas treatment – HIV+ women Recommended Regimen for Women with HIV Infection Rescreen in 3 months (ideally with NAAT) Metronidazole 500 mg orally twice daily x 7 days

18. Tip #6- Employ Newer Testing Options for Trich • Microscopy is inferior to new options, including • Rapid antigen testing (OSOM) • Nucleic acid amplification testing • APTIMA TMA Trichomonas vaginalis assay • May use same specimen types as used with gc/chl NAATs (i.e. vaginal swab, endocervical swab, urine) Huppert CID 2007 Test Sens Spec APTIMA TMA 98% 98% OSOM 90% 100% Culture 83% 100% Wet prep 56% 100% Slide adapted from Marrazzo, IDSA 2011

19. Mr G.P. lets one of his male partners know about the STD contact. Mr. O.S. comes to your clinic for GC screening and treatment. What else can you offer? • GC pharyngeal NAAT; GC/CT urine and rectal NAAT • Syphilis serology • Hepatitis B/C • HIV testing • Vaccination (Hep A/B, HPV) • PrEP 10

20. High burden of bacterial STIs /PrEP settings McCormack Lancet 2016 Molina NEJM 2015 Baeten NEJM 2012

21. Tip #7- Screen for bacterial STI in PrEP clinic !

22. Rethink CDC PrEP STI q 6 month screening guidelines? • 21% incident STI in 6 months prior to PrEP start • Relying on symptoms would miss • -77% of STI at 3 months • -68% of STI at 9 months • “Repeat” patients responsible for bulk of incident infections Golub, S, et al, Abstract #869 CROI, 2016

23. Case continues • Mr. O.S. has full STI screen and baseline HIV test, gets GC exposure treatment and starts daily tenofovir/emtricitabine. 3 months later he returns for an evaluation and STI screen is repeated. He reports he can barely read the instructions in the bathroom about self-obtaining rectal swab due to a recent ‘blurriness’ in his L eye. • 2 days later his Syphilis EIA returns POSITIVE with reflex RPR of 1:256. He admits to a suspicious rash two weeks ago which has now resolved. His rectal CT NAAT is positive. Management??

24. Rates of infectious syphilis rising in MSM especially HIV+ 10-55% HIV coinfected • Prevalence (2011) • 2.6% in HIV-negative MSM • 10.1% in HIV-positive MSM • 75% of all P & S syphilis in MSM • Core group of HIV+ MSM disproportionately contribute

25. Tip #8- Neurologic complaints should prompt consideration of neurosyphilis • Symptoms • Visual changes, hearing loss, facial weakness, stuttering stroke symptoms • Entities- Symptomatic early neurosyphilis (SENS) • Ocular- uveitis, chorioretinitis most common • Otic- tinnitus, SNHL • Cranial Nerve involvement • Aseptic meningitis • Meningovascular

26. Syphilis- When to do an LP? • Signs or symptoms of neurosyphilis • Diagnosis of Tertiary syphilis • May benefit? -Not serologically responding to treatment (eg-4-fold drop 6-12 months in early syphilis) Interpretation: • Si/sx and Pos CSF-VDRL= diagnostic of neurosyphilis • Si/sx with abn CSF (prot >40, WBC >5) with NEG CSF-VDRL = consider neurosyphilis. Negative CSF-TPPA virtually excludes neurosyphilis CDC STD Tx Guidelines 2015

27. Case continued- Mr OS has LP, posterior uveitis confirmed by ophthalmologic exam, high dose IV penicillin started for ocular syphilis/neurosyphilis. Key points- • Serologic follow up @ 3,6,9,12,24 months • Counsel about Jarisch-Herxheimer reaction • Report to local Health Department within 24 hours of diagnosis (CDC Advisory Feb 8, 2016) • Pre-antibiotic samples (whole blood , primary lesions, CSF or ocular fluid) saved and stored at -80 immediately on collection (for assistance contact Dr Allan Pillay at 404-639-2140 or ajp7@cdc.gov)

28. Tip #9- Treatment regimen for rectal CT depends upon symptoms Scenario A: Rectal CT NAAT positive- asymptomatic pt Treat for uncomplicated CT Azithromycin 1 gm po x 1 or Doxycycline 100 mg po bid x 7 days* Scenario B: Rectal CT NAAT positive- symptoms of proctitis Treat for presumed LGV strain Doxycycline 100 mg po bid x 21 days • Further testing to confirm?- LGV strain PCR not commercially available. • NYC diagnostic LGV conundrums contact Dr Julie Schillinger (jschilli@health.nyc.gov) *may be superior in rectal CT infections?? RCT needed

29. Tip #10! Want to know more about STDs? There’s an app for that. CDC STD Treatment Guidelines App for Apple and Android Available now, FREE! (accept no competitors) Search “STD Treatment” in App store Download now! 

30. National- STD Clinical Consultation Network (STDCCN) • NEW!!!!! • Provides STD clinical consultation services within 1-5 business days, depending on urgency, to healthcare providers nationally • Your consultation request is linked to your regional PTC’s STD faculty • Just a click away! • www.STDCCN.org

31. Top Ten Tips to Take To Work Remember to screen patients for STIs in your HIV clinic Screen MSM and at risk heterosexuals in all sites, frequently Employ dual treatment for Gonorrhea Rescreen for bacterial STI in 3-4 months EPT is effective and legal in your state Trichomonas diagnostics have improved- access them PrEP setting STI rate high- screen often Syphilis rates remain high; ask about neurologic symptoms Symptoms drive treatment regimen of rectal CT infection in MSM Fast resources available- Download the App THANK YOU!

32. EPT information • National- www.cdc.gov/STD/EPT • New York -http://www1.nyc.gov/site/doh/health/health-topics/expedited-partner-therapy.page • New Jersey-http://www.nj.gov/health/std/documents/ept_facts.pdf • Connecticut-http://www.ct.gov/dph/lib/dph/infectious_diseases/std/ept_clinical_advisory.pdf

33. EPT- Practical Considerations in NYS • Write “EPT” in body of script • Can leave patient name, DOB, address blank and pharmacists can fill it • DO NOT use for partners of patients w GC, syphilis • Provider must • provide index patient w/ written materials • Counsel index patient to tell partner to read material • More info on website • Fully electronic prescribing- end of March- stay tuned for EPT exception

34. Back-Pocket GC Treatment Regimens: Alternatives for cephalosporin-allergic patients • Trial conducted in Baltimore, Birmingham, Pittsburgh, San Francisco • 401 men and women 15 - 60 yrs • 202 received gent 240 mg IM + azithro 2 g PO: 100% effective • 199 received gemiflox 320 mg PO + azithro 2 g PO: 99.5% effective • Bottom line • Probably fine for urogenital gonorrhea, but trial not powered for extra genital gonorrhea (though it worked in the few cases enrolled) • Efficacy limited by tolerance: 8% vomited in the gemiflox + azithro group and needed re-treatment with standard cftx + azithro Kirkcaldy RD et al. CID 2014