Hot Topics Adult Infectious Diseases 2018 Wayne Ghesquiere MD FRCPC

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1 Hot Topics Adult Infectious Diseases 2018 Wayne Ghesquiere MD FRCPC Infectious Diseases Consultant Island Health Authority Clinical Assistant Prof of Med, UBC Victoria

2 Faculty/Presenter Disclosure Wayne Ghesquiere Faculty: Clinical Assistant Prof of Medicine, UBC Relationships with commercial interests: None Research support: AbbVie, BMS, GSK, Jansen, Merck, Speakers bureaus/honoraria: AbbVie, GSK, Merck, Pfizer, Sanofi Pasteur Consulting fees: None Other: None

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6 What will be reviewed: Syphilis PrEP Zoster Vaccines

7 Syphilis Dramatic increase in Treponema pallidum infections since 2013 Throughout the world, especially in the MSM population Screening serology has changed, brought in the EIA which is more specific and more sensitive for all stages of the disease Increase in ocular syphilis and it s not likely due to an overall increase in syphilis. Neurosyphilis is also on the rise.

8 Infectious Syphilis Cases in BC and Canada 1991 to 2015

9 Reported overall rates by gender of Infectious Syphilis cases , Canada

10 Slide courtesy of Dr. Troy Grennan, BCCDC Infectious syphilis in BC by risk category, Total Cases 2011: : : : : : :

11 New Test: Treponemal CLIA (EIA) Chemiluminescent immunoassay test. Detects both IgM and IgG antibodies to syphilis. High sensitivity and specificity of detection at all stages of disease (>99% for both). False negatives: most likely to occur very early in infection. False positives: most likely to occur in low risk populations.

12 Year

13 Ocular Syphilis on the Rise

14 Ocular Syphilis Seen in both HIV + and HIV patients. Can occur within 6 weeks of infection. Manifestations of uveitis, keratitis, optic neuritis, retinitis, vasculitis. When diagnosed screen for other STI s, HIV, consider an LP. Treat with antibiotics, topical and possibly systemic steroids.

15 Treatment of Syphilis

16 Pre-Exposure Prophylaxis (PrEP) Use of antiretrovirals (ARVs) by HIV negative individuals to prevent HIV infection before (and after) potential exposure to HIV

17 Ipergay : Event-Driven or On Demand iprep ü 2 tablets (TDF/FTC or placebo) 2-24 hours before sex ü 1 tablet (TDF/FTC or placebo) 24 hours later ü 1 tablet (TDF/FTC or placebo) 48 hours after first intake Friday Saturday Sunday Monday Tuesday Wednesday Thursday Friday Saturday Sunday

18 IPERGAY: Results 16 subjects infected PBO=14 (incidence: 6.6/100 PY) TVD=2 (incidence: 0.94/100 PY) Mean follow-up=13 months Average 16 pills / month Probability of HIV-1 infection Placebo P = TDF/FTC Months 13% TDF arm used NPEP 11% placebo arm Placebo, n TVD, n *mitt Population Log-rank test % (95% CI: 40-99, p=0.002) reduction in MSM at high risk of HIV infection who took on-demand PrEP

19 Evidence for PrEP - MSM Trial Study size Risk Reduction Number needed to treat annually to avert HIV case IPrEx 2499 (incidence 3.6/100 PY placebo arm) 44% overall 92% in those with detectable drug level 62 overall 36 if CAS PROUD IPERGAY 545 (incidence 8.9/100 PY deferred arm) 414 (incidence 6.6/100 PY) 86% overall 13 86% overall 18 Grant, R. NEJM 2010;363: McCormack, S. Lancet 2016;387:53 Molina J, et al. NEJM 2015;373: 2237.

20 How to use Truvada for PrEP Two ways: 1. On Demand - Take 2 tablets, 2 hours before sexual activity then 1 tab daily for 2 days (hence 4 tabs in total) 2. Long term prevention - Take 1 tablet daily for as long as individual remains at risk.

21 PrEP Monitoring Baseline: HIV and other blood tests Start prescription for 30 days: daily use? Ondemand? First Follow-up: Just before end of first month of use Check HIV, renal, liver tests again BC CfE PrEP Guidelines Get prescription refill: 90 days Every 3 months HIV/renal/STI checks

22 Shingles Vaccines There are now two choices: 1. Live attenuated Oka strain (Zostavax) 2. Non-live subunit vaccine with novel adjuvant (Shingrix)

23 Randomized Double-blind, placebo-controlled, multicenter trial (22 US sites) Enrolled 38,546 subjects ³ 60 yrs ; age-stratified Follow-up a median 3 yrs Vaccine efficacy was: 61.1% (95% CI, %) for burden-of-illness score 51.3% (95% CI, %) for confirmed zoster incidence 66.5% (95% CI, %) for post-herpetic neuralgia

24 Overall Efficacy of the Zoster Vaccine 25%=prespecified lower bound success criterion Zoster PHN BOI 51.3% 61.1% 95% CI 66.5% Vaccine Efficacy (%) 1. Oxman MN et al. N Engl J Med 2005;352:

25 The AE Monitoring Sub-study AE Injection Site Erythema* Pain / tenderness* Swelling* Hematoma Pruritus Warmth Zoster Vaccine (N=3345) % Placebo (N=3271) %

26 ZOSTAVAX [Zoster Vaccine Live (Oka/Merck)] Product Profile Live, attenuated varicella-zoster virus vaccine Minimum of 19,400 PFU* per dose No preservative Lyophilized product Same excipients as VARIVAX [Varicella Virus Vaccine Live (Oka/Merck)] Single subcutaneous dose *PFU = plaque-forming units

27 Conclusions. CID 2015:60 (15 March) Morrison et al Estimates of vaccine efficacy decreased over time in the LTPS population compared with modeled control estimates. Statistically significant vaccine efficacy for: HZ BOI persisted into year 10 post-vaccination. Vaccine efficacy for incidence of HZ persisted only through year 8.

28 Clinical trial of a HZ vaccine called ZOE 50 and ZOE 70 Efficacy years of age 95% years of age 90% 80 years and older 89%

29 HZ/su Vaccine (Shingrix)

30 Solicited Local Symptoms Within 7 Days Post-Vaccination

31 Solicited Systemic Symptoms Within 7 Days Post Vaccination

32 Zostavax (2006) Shingrix (2017) Indications HZ prevention >50y HZ prevention >50y Composition Live-attenuated Non-live subunit vaccine with novel adjuvant Route of Administration SC IM # doses 1 2 given 2-6m apart Efficacy at HZ prevention ~70% in 50-59yo; ~51% in >60yo ~37% in >80yo 95% in 50-69yo 90% in 70-79yo 88% in >80yo Reduction in Burden of Illness ~73% Prevention in PHN 88.8% AE profile ~48% injection-site reactions ~81.5% local and ~66% systemic reactions, of which ~15.6% were grade 3 reactions Real World Efficacy data Yes None- vaccine is new Duration of protection At least 5-7y in real world 4y in clinical trial NACI recommendation Yes- adults >50y Pending Recommendations for immunocompromised Yes- certain subsets Use in prior HZ Yes- 1 y later Yes 1 y later Yes Need to check VZV serology No No

33 Common Vaccine Questions Q:How long does the vaccine last and do I need to revaccinate? A: According to Health Canada we do not need to revaccinate. Q: How long should one wait after an episode of HZ for immunizing with the zoster vaccine? A: Health Canada recommends waiting 6-12 months

34 Common Questions Q: Does the zoster vaccine benefit patients who have already had zoster? A: ACIP recommends that persons who report a previous episode of zoster can be vaccinated. Q: Can a patient who has had the live virus vaccine be immunized with the HZ/su vaccine? A: Yes recommended by ACIP, awaiting NACI.

35 Thank You Questions?