HIV & STI Care & Prevention: Update for the Generalist Providence St. Vincent Medical Center

1. HIV & STI Care & Prevention: Update for the Generalist Providence St. Vincent Medical Center September 23, 2014 Jeanne Marrazzo, MD, MPH Seattle STD/HIV Prevention Training Center University of Washington The New Yorker, October 1, 2012

2. Today’s Discussion • Top 10 (or so) areas to be aware of in diagnosis, management & prevention • Chlamydia, gonorrhea, syphilis, genital herpes, HPV • Integrated approaches to HIV prevention

3. The syphilis epidemic in men who have sex with men continues (and can present in confusing ways)

4. My patient • 23 yo man; healthy; marathon runner; last HIV test negative 1.5 y ago • Unilateral hearing loss: April 2010 • Sought primary care May 2010; referred to otolaryngology June 2010 • Audiogram revealed bilateral hearing loss (30% reduction), symmetric; no other neurologic abnormalities; normal MRI • In follow-up for hearing loss, another otolaryngologist ordered RPR July 2011: +1:128 • Referred to ID specialist

5. My patient • Seen by ID August 2010; treated with 3 doses of BZN PCN for “syphilis” • Seen in STD Clinic October 2011 for routine screening; new diagnosis of HIV • Enrolled in neurosyphilis study and treated with parenteral PCN x 2 weeks; repeat LP negative • Referred to me for HIV care October 2010 • CD4 495 (22%) • HIV RNA 56,000

6. http://www.cdc.gov/std/stats12/default.htm Primary and Secondary Syphilis by Sex and Sexual Behavior, 33 areas,* 2007 - 2012

7. Syphilis: Stages 1º Chancre

8. Syphilis: Stages 1º 2º Chancre Rash, fever, neurologic symptoms

9. Significant symptomatic neuroinvasive disease, especially auditory and ocular neuropathy Syphilis in HIV: Manifestations May Be Protean,More Severe, and More Invasive Luesmaligna in an HIV-seropositive man Li. CID. 2009; Wang. Intl J STD AIDS. 2012

10. Syphilis: Clinical FeaturesLatent Stage • Defined by positive treponemal serology in the absence of clinical manifestations • <1 year: early latent • >1 year: late latent • 2/3 of persons with untreated syphilis remain in latent stage for life

11. reflex to • Syphilis Screening Paradigm TRADITIONAL EMERGING / NEW… • Non-treponemaltests (eg, RPR, VDRL) • NON-SPECIFIC ANTIBODY TO LIPOIDAL ANTIGENS • QUANTITATIVE • REACTIVITY DECLINES WITH TIME • Treponemal tests (e.g., TPPA, FTA-Abs • SPECIFIC TO TP • QUALITATIVE • REACTIVITY PERSISTS OVER LIFETIME • Treponemal tests (eg, EIA, CIA, MBIA) • SPECIFIC TO TP • QUALITATIVE • REACTIVITY PERSISTS OVER LIFETIME • Non-treponemal tests (e.g., RPR, VDRL) • NON-SPECIFIC ANTIBODY TO LIPOIDAL ANTIGENS • QUANTITATIVE • REACTIVITY DECLINES WITH TIME Abbreviations: EIA, enzyme immunoassay; CIA, chemiluminescent immunoassay; MBIA, microbead immunoassay; RPR, rapid plasma reagin; VDRL, Venereal Disease Research Laboratory Slide 11 of 77

12. Syphilis EIA/CIA • Treponemal tests FDA cleared for clinical use • IgG, IgMtests available • IgMin early syphilis diagnosis (Knaute. CID. 2012) • Automated, occupational advantages (no pipette), no prozone, less costly to lab • “Reverse sequence syphilis screening” is result (treponemal test used first) • Limitations: • Can’t distinguish between active and old disease (treated/not) • Can’t use to monitor therapy (no titers) • False positive results in low prevalence Sena. Clin Infect Dis. 2010; Park. J Infect Dis. 2011

13. Negative Positive Not Syphilis Non-trep test (RPR) Positive Negative 2ndTrep Test Syphilis (past or present) Negative Positive 1) Unconfirmed EIA Unlikely syphilis; if patient at risk, retest in 1 month • Past Syphilis • Early Syphilis Reverse Sequence Screening Algorithm EIA or CIA Slide courtesy of Ina Park, MD

14. 2. More chlamydia infections were reported to CDC in 2012 than in any previous year (>1.4 million)

15. Diagnostic Testing • Nucleic acid amplification tests (NAAT) recommended for CT/GC in men &women • Optimal specimen types are first-catch urine in men, and vaginal swabs in women • NAAT optimal for rectal and pharyngeal testing; not validated by FDA but commercially available & validation protocols available • Repeat testing of +NAAT not needed www.aphl.org/aphlprograms/infectious/std/Documents/CTGCLabGuidelinesMeetingReport.pdf

16. Chlamydia NAATs

18. 2010 CDC STD Treatment Guidelines:Uncomplicated Chlamydial Infection • Recommended • Azithromycin 1 g PO, single dose, directly observed • Doxycycline 100 mg PO BID x 7 d • Alternatives • Ofloxacin 300 mg PO BID or levofloxacin 500 mg PO qD x 7 d • Erythromycin 500 mg PO QID x 7 d NOTE: Ciprofloxacin not effective Routine test of cure not indicated, but… REPEAT testing in 3-6 months

19. 3. Antimicrobial resistance in gonorrhea is here

20. International Emergence of N gonorrhoeae with Decreased Susceptibility to Cephalosporins • Increasing proportion of isolates with laboratory evidence of decreased susceptibility (GISP) • Elevated MICs • Case reports of oral cephalosporin treatment failures • East Asia and Western Pacific, 2000-present • Europe, 2010-present • N. America, 2010-2011: Cefixime treatment failure in 25% with MIC >0.12 (Allen 2013) • Extended Spectrum Cephalosporin Resistance • H014: Japanese sex worker with pharyngeal isolate with ceftriaxone MIC 2-4 (Ohnishi 2011) • F89: French MSM urethral isolate with cefixime MIC 4, ceftriaxone 1-2 (Unemo 2012)

21. Percentage of GISP Isolates with Elevated Ceftriaxone MICs (≥0.125 µg/ml), 2008–2012* Percentage of isolates Year * Preliminary (Jan-June) Source: Gonococcal Isolate Surveillance Project

22. Percentage of Isolates with Elevated MICs or Resistance by Sex of Sex Partner, 2005 - 2010 * ≥ 0.125 µg/mL ** ≥ 0.25 µg/mL † ≥ 2.0 µg/mL ‡ ≥ 1.0 µg/mL Kirkcaldy. Ann Int Med. 2012

23. CDC STD Treatment Guidelines Uncomplicated Gonococcal Infections of Cervix, Urethra & Rectum Ceftriaxone 250 mg as a single intramuscular dose (Or if not an option, Cefixime 400 mg orally in a single dose) PLUS Azithromycin 1 g orally or Doxycycline 100 mg twice daily for 7 days

24. Cephalosporin Treatment Failures • Recommendations • Infectious disease consultation • Culture and susceptibility • Ceftriaxone 250 mg IM + 2 gmazithromycin • Ensure partner treatment • Test of cure one week after treatment • Report to CDC via state or local public health CDC STD Treatment Guidelines 2010, MMWR 2011

25. …Test of Cure • 7 days post-treatment; culture or NAATChallenges • Local guidelines may differ • Resources • Few data inform likelihood of negative test in adequately treated infection at 7 days (Bachmann 2002; Hjelmevoll SO 2012) MMWR Aug 10, 2012; 61 (31)

26. Rectal and Pharyngeal Infections are Commonly Asymptomatic Chlamydia n = 655 Gonorrhea n = 892 Proportion of infections that would NOT be identified if only urine/urethral screening is performed among gay/bisexual men (Kent et al. CID 2005 updated)

27. STD Screening:Requires asking Slide #27 www.nnptc.org/online_training/asi

28. 4. Most new genital herpes infections are caused by HSV-1

29. Natural History of HSV in the Herpevac Trial Rate of infection with HSV-1 nearly twice that of HSV-2 (2.5 vs. 1.1%) No difference in clinical severity Most new infections were asymptomatic (74% HSV-1, 63% HSV-2) Younger participants more likely to have asymptomatic infection 84% of recognized infections were genital Bernstein, Clin Infect Dis 2013:56

30. Symptomatic Genital Herpes: Tip of the Iceberg • General U.S. seroprevalence16.2%; MSM ~50% • 50 million in U.S. infected; ~90% unrecognized MMWR April 23, 21010; Xu, JAMA 2006; Photo: J. Hofmann

31. Type-Specific gG-Based HSV Serology: Commercial Kits 2013 Sensitivity Specificity HerpeSelect-2 ELISA (Focus) 96-100* 97-100 HerpeSelect Immunoblot (Focus) 97-100 98 HerpeSelect Express (Focus) 86-100 97-100 biokitHSV-2 (biokitUSA ) 93-100 94-97 Cobas-HSV-2 (Roche) 93 98 Captia Select-HSV-2 (Trinity) 90-92 91-99 • Cost varies; $30-$180 • Western blot assay, considered gold standard, available through University of Washington

32. HSV Type-Specific SerologyLimitations Does not tell How long infected If person has had or will have symptoms How likely a person is to shed asymptomatically Where infected (HSV-1) Cannot diagnose a lesion False positives Decreased PPV in low prevalence populations AND in patients with HSV-1 infection False negatives 77% of patients have antibodies by 6 weeks after HSV-2 primary infection and 59% after HSV-2 non-primary infection

33. 5. The HPV vaccine is already working!

34. Markowitz L, J Infect Dis 2013: 308

35. Genital warts in young Australians five years into national human papillomavirus vaccination programme: national surveillance data Ali H, BMJ 2013: 346

36. Anal Dysplasia and Cancer • HIVMA / IDSA primary care guidelines: anal Papanicolaou (Pap) test if history of receptive anal intercourse, abnormal cervical Pap, genital warts: weak recommendation, moderate quality evidence • Patients with abnormal results should be evaluated with high-resolution anoscopy • Human papillomavirus (HPV) DNA screening not recommended; role not defined • Vaccinate against HPV: safe and immunogenic in HIV+ • Prevents anal cancer, AIN 2-3 Toft, JID. 2013

37. 6. New tools to prevent HIV acquisition

38. Biomedical Prevention: What Is It? A biological intervention that modifies a person’s risk of acquiring disease or condition in future • However… behavioral component may be critical: • Many preventive medications (malaria) to lower risk are biomedical interventions, but still require behavioral effort: acquiring & taking the drug • Perceptions of efficacy and risk of adverse outcomes are related to likelihood of compliance with intervention

39. HIV Prevention in Clinical Care Settings: 2014 Recommendations of the International Antiviral Society-USA Panel Free web access to the paper at jama.com

40. Efficacy of Biomedical Interventions to Prevent HIV Acquisition: Summary of the Evidence from Randomized Clinical Trials Modified from Ambitious Treatment Targets: Writing the Final Chapterof the AIDS Epidemic, UNAIDS, 2014.

41. MMWR May 16, 2014 / 63(19);437 *caveat on discussion for peri-conception counseling

42. Who Should Get PrEP?CDC 2014

43. 7. There’s a new era in technology!

44. Download the CDC STD treatment guidelines app …

45. Slide #45 STD Resources • Seattle STD/HIV Prevention Training Center • www.seattlestdhivtraining.org • National Network of STD/HIV Prevention Training Centers • www.stdhivpreventiontraining.org • CDC Treatment Guidelines • www.cdc.gov/std/treatment • American Social Health Association (ASHA) booklets, books, handouts, the Helper www.ashastd.org(800) 230-6039 • ASHA patient herpes hotline (919) 361-8488

46. Take-Home Messages • Screen, appropriately! • Rescreen for chlamydial and gonococcal infections 3 to 6 months after initial + • Be aware of antibiotic-resistant GC • Syphilis: it’s not going away. Know what the EIA is and recognize neuroinvasive disease • Sexual health • Vaccinate for HPV (but continue Pap test screening) • Prevention messages

47. THANK YOU!!

48. Primary, secondary and early latent BZN PCN (L-A) single dose IM 2.4 million units Do not use other PCN formulations! Do not use azithromycin Doxycycline 100 mg PO bid x 14 days (inferior) Ceftriaxone 1 g IV or IM daily x 8-10 days (alternative) Late latent BZN PCN IM 2.4 million units weekly x 3 doses (7.2 million u total) Doxycycline 100 mg PO bid x 28 days (inferior) Neurosyphilis Aqueous PCN G 18-24 million units/day x 10-14 days Procaine PCN G 2.4 million units/day PLUS probenecid 500 mg PO qid x 10-14 days Ceftriaxone 2 g IV daily x 10-14 days (alternative) Syphilis: Treatment 2014 CDC STD Treatment Guidelines www.cdc.gov/std; Ghanem K. Clin Infect Dis. 2011