5th CEE MEETING ON VIRAL HEPATITIS AND HIV

Vaccinations for HIV patients: which when and how? Carolynne Schwarze-Zander 20.09.2019 WHO Ten Threats to Global Health

6. Ebola and 1. Air Pollution and Climate Change Other High Threat Pathogens

2. Non Communicable Diseases 7. Weak Primary Healthcare

3. Global Influenza Epidemic 8. Hesitancy

4. Fragile and Vulnerable Settings 9. Dengue Virus

5. Antimicrobial Resistance 10. HIV Disagreeing with „Overall I think are safe“

https://www.vaccineconfidence.org/research/the-state-of-vaccine-confidence-2016/ Interactive Country Data Viewer

France 41%

Bosnia & Herzegovina 36%

Russia 28%

https://www.vaccineconfidence.org/research/the-state-of-vaccine-confidence-2016/ 5 C Modell

Confidence

Constraints

Complacency

Calculation

Collective Responsibility

Betsch et al., Bundesgesundheitsblatt 2019 Vaccinations in PLWH

Vaccinate according to national guidelines

Infection Rationale Hepatitis A According to risk: travel, MSM, IVDU, HBV/HCV coinfection, long viremia

Hepatitis B Shared risk with HIV, HIV accelerates course of liver disease HPV Shared risk with HIV, higher rate of cervical and anal cancer Influenza Higher rate of pneumonia As general population Streptococcus pneumoniae Higher rate and severity of invasive disease Varizella Zoster Higher rate and severity of both chicken pox and zoster

EACS Guidelines 2018 Expected Succes of in PLWH

CD4+ T- Expected Vaccination CDC Stage Lymphocytes/μl Response >500 normal A1, B1 200-499 good A2, B2, C2 <200 reduced A3, B3, C3

Ehl S et al. Bundesgesundheitsblatt 2018 Influenza

Annual Vaccination Recommended composition of influenza virus vaccines 21 February 2019 (updated on 21 March 2019)

Blue: composition of trivalent vaccines Red: composition of quadrivalent vaccines

https://www.who.int/influenza/vaccines/virus/recommendations/2019_20_north/en/ Distribution of influenza virus subtypes by influenza transmission zone, September 2018 to January 2019

https://www.who.int/influenza/vaccines/virus/recommendations/201902_recommendation.pdf?ua=1 Relative proportion of Influenza B viruses vary

RKI Saisonberichte 2001/2002-2017/2018. https://influenza.rki.de/saisonbericht.aspx Cocirculation of Influenza B-lineages 2001-2018 Match und Mismatch

RKI Saisonberichte 2001/2002-2017/2018. https://influenza.rki.de/saisonbericht.aspx Unsolved Problem: Vaccination Coverage

ecdc.europa.eu 2018 Unsolved Problems: Low Seroprotection and Supply

Studie Vakzine Seroprotektion

Bickel et al. 2010 Vakzine + AS03 75% Shortage of influenza vaccines Canestri et al. 2010 Vakzine + AS03 92% in many parts of Germany Cooper et al. 2011 Vakzine + AS03 80%

Crum-Cianflone et al. 2011 Vakzine 67%

Fabbiani et al. 2011 Vakzine + MF59 78%

Schwarze-Zander et al. 2015 Vakzine + AS03 66%

Soonawala et al. 2011 Vakzine + MF59 88%

Tebas et al. 2010 Vakzine 61%

Tremblay et al. 2011 Vakzine + AS03 45%

Yanagisawa et al. 2011 Vakzine 62%

Tsachouridou Human Vaccines & Immunotherapeutics 2018 , GA Bonn 21.12.2018 Universal Flu Vaccine

M-001

designed to provide multi-season and multi-strain protection Streptococcus pneumoniae

One dose of conjugated 13-valent vaccine PCV; no general recommendation for booster dose Some national guidelines consider one dose of polysaccharide vaccine PPV-23 Prevenar 13® (PCV) and Pneumovax 23® (PPV)

PPV induces Hyporesponsiveness:

Prevenar 13® (PCV) PCV/PCV

PCV/PPV Pneumovax 23® (PPV) PPV/PCV Retrospective study evaluating risk of PnI between 1996-2004

• 12 times higher risk with a nonvirologically suppressed (107 vs. 9/100 000 Patienten) • Lower risk among virologically suppressed HIV patients (7.6 vs. 9/100 000 Patienten)

Lesourd et al. Open Forum Infect Dis 2016 27 studies on IPD in HIV patients • 19 advanced ART • 13 early ART • 10 pre-ART

Pre-ART (before 1996)

Early-ART (1996-2000)

Advanced-ART (after 2000)

Travel Med and Infect Dis 2018 Neisseria meningitidis

As general population Conjugated vacvine (2 doses 1-2 months apart), booster every five years Worldwide disribution of Serogroups of Neisseria meningitidis Invasive Meningococcal Disease in MSM

New York Québec

Los Angeles

Paris

Chicago Berlin Invasive Meningococcal Disease in MSM in Germany 2012- 2014

Hellenbrand et al. PLOS ONE 2016 Meningococcal B vaccine

Bexsero® 4CMenB Trumenba® rLP2086

Suspension composed of 4 distinct antigens Suspension of 2 recombinant lipidated factor • NHBA (Neisserial heparin-binding Antigen) H binding ptotein variants fusion protein • NadA (Neisserial adhesion A)-protein • fHbp subfamily A • fHbp (factor H binding protein) subfamily B • Outer Membrane Vesicle (OMV) • fHbp subfamily B N. Gonorrhoeae and N. meningitidis: 80-90% genetic homology

Retrospective Case-Control Study in New Zealand after MeNZB Vaccination (Outer membrane vesicle)

Adjusted OR Vaccine effectiveness (95% CI)

vaccinated vs. non- 0.69 (0.61- 31% (21-39) vaccinated 2004- 0.79) 2014

Petousis-Harris et al. Lancet 2017 HPV

Vaccinate with 3 doses uo to age 26/age 40 if MSM Use 9-valent vaccine

If HPV infection is established, efficacy of vaccine is questionable Prevalence of HPV associated Carcinomas

100% 88% 43% (Vulvar carcinoma) - 70% (Vaginal carcinoma) 50% 13-56% tonsils > 50%

Approx. 5% of all human carcinomas are caused by HPV infection (HPV16 und HPV18)

de Martel Lancet Oncol, 2012 HPV Vaccines

https://www.pei.de/DE/arzneimittel/impfstoff-impfstoffe-fuer-den-menschen/hpv-humane-papillomviren-gebaermutterhalskrebs/hpv-humane- papillomviren-gebaermutterhalskrebs-node.html Safety and Immunogenicity of 4v-HPV-Vaccine in PLWH

• 126 HIV positive patients, age: 7-12 years

• CD4 >15%, on ART

• Seroconversionrate for all 4 antigens 96%

• Geometric means of the titers lower

Clinical relevance of lower immune response unknown

aus Fachinformation ®9 HPV Prevalence in HIV+ MSM

Author Country HPV Prevalence in HIV+ MSM Li et al.2016 China 71% Cranston et al. 2018 USA, Thailand, Peru, 93% South Africa Hernandez et al. 2016 India 95% Kreuter et al. 2005 Germany 93% Fuchs et al. 2016 Germany 82% • Phase 3, randomized, double-blind, controlled trial • 3 vaccinations with quadrivalent HPV vaccine (types 6,11,16,18) or placebo in HIV+ Patienten ≥27 years • 575 participants (82% men, 18% women), 558 Patienten 3 Impfungen erhalten • Mean age 47 years • CD4 602/ul, 83% HI-viral load <40 copies/ml

➢ HPV vaccination in PLWH ≥27 no influence on prevention of new anal HPV lesions or improvement of anal HSIL

➢ Role for prevention of oral HPV

Wilkin Clin Infect Dis 2018 Zoster Herpes Zoster PHN Incidence in Germany

Epidemiologisches Bulletin Nr.50, 12.2018, Hildebrand et al. J Infect 2017 Higher risk of HZ in patients with immunsuppression

Bone marrow transplant: 4-7-times

Chronic HIV infection: 3-5-times

Patients with solid tumors: 4-times

Patients after organ transplantation: 7-times

Forbes et al. BMJ 2014 Shingrix®

Immunogen: lyophilized varicella zoster virus glycoprotein E (gE)

Adjuvans: AS01B adjuvant suspension component Monophosphoryl-Lipid (MPL) A von Salmonella Minnesota Quillaja saponaria Molina Soap bark tree ZOE-50 und ZOE-70

Study ZOE-50 ZOE-70 (Lal et al. NEJM 2015) (Cunningham et al. NEJM 2016)

Randomisierte, doppelblinde, placebokontrollierte, multizentrische Studien in Study design mehreren Ländern (Nordamerika, Europa, Lateinamerika, asiatisch-pazifischer Raum)

Primary endpoint HZ-efficacy in paticipants ≥ 50 years HZ-efficacy in participants ≥ 70 years

Primary target in PZN-efficacy ≥ 70 years pooled analysis HZ-efficacy ≥ 70 years

Study participants 16.160 14.816

Take home messages

Vaccination is the best strategy of prevention

Vaccinate according to national guidelines

Remember higher risk in HIV patients for • HAV • HBV • HPV • Influenza • Neisseria meningitidis • Streprococcus pneumoniae • Varicella Zoster