Vaccination schedule of HIV patients: an update

Transcription

1 INFECTIOUS DISEASES DEPARTMENT AIDS REFERENCE CENTRE Vaccination schedule of HIV patients: an update BREACH symposium, Nov N. Dauby, Ch. Martin CHU Saint-Pierre, Brussels 1

2 Plan 1. Mechanisms of defective vaccine response during HIV infection 2. Vaccine schedule : current recommandations and recent data 3. Vertically-infected young adults : a special population

3 Pathways to antibody production : role of germinal centers Linterman & Hill 2016

4 Vaccine response in HIV-infected subjects : mechanisms of dysfunction T Follicular Helpter T cells (Tfh) dysfunction HIV-infected Different phenotype B cell dysfunction Exhausted & activated B cells Lower response to proliferation Persistent Immune activation on ART Lower rate of seroconversion after vaccination Lower persistance of vaccine-specific antibody

5 15 HIV+ on cart 3.6 years on ART CD4 711/µL CD4/CD8 ratio Healthy donors

6 Higher % of Tfh Higher expression of SLAM & ICOS Higher level of cell death at baseline

7 Predictors of serological responses to trivalent influenza vaccine in HIV+ subjects on ART Negative correlation scd25 CD38+HLA-DR+ICOS+Ki-67+PD-1+ (% of ptfh) CD38+HLA-DR ICOS Ki-67+PD-1+ (% of ptfh) IL-21 Positive correlation CD38+HLA-DR+ICOS+Ki-67+PD-1 (% of ptfh) CD38 HLA-DR ICOS+Ki-67+PD-1 (% of ptfh) CD38 HLA-DR (% of CD8) TCM (% of CD4) De Armas JCI insight 2017

8 Early cart preserves both B and Tfh compartments Early ART Chronic ART Memory B cells Tfh cells Moir et al Blood 2010 Planchais et al J Immunol 2018

9 Plan 1. Mechanisms of defective vaccine response during HIV infection 2. Vaccine schedule : current recommandations and recent data 3. Vertically-infected young adults : a special population

10 10

11 New CSS/HGR recommendations: pending Categories: Announced changes: Actively recommended (A) Risk dependant (R) Standard indications (S) Contraindication (CI) -appearance of MenACWY, MenB, inactivated Zoster -MenC/MenACWY: switch S R -HPV: switch R A -MMR: switch R S -VZV: switch R A 11

12 New CSS/HGR recommendations: pending Categories: Announced changes: Actively recommended (A) Risk dependant (R) Standard indications (S) Contraindication (CI) -appearance of MenACWY, MenB, inactivated Zoster -MenC/MenACWY: switch S R -HPV: switch R A -MMR: switch R S -VZV: switch R A 12

13 Review Clin Infect Dis 2014 Med follow-up 9mo-9years Med 40 pts/study 13

14 Measles immunization (MMR) 10 children studies, 2 adults studies Metaanalyse 5 children studies 68% still protected>2y 40% >5y Adult data: 95% still protected if immunized during childhood (= before HIV) 43% still protected 1y after vaccination if vaccinated during adulthood 14

15 Measles immunization (MMR) Metaanalyse 5 children studies 68% still protected>2y 40% >5y 10 children studies, 2 adults studies Nadir CD4 T cells count predicts functionnal responses to immunisations in chronic HIV infection, even after years of suppressive antiviral therapy Adult data: 95% still protected if immunized during childhood (= before HIV) 43% still protected 1y after vaccination if vaccinated during adulthood Lange et al. AIDS 2003, 17:

16 Respect Innovation Engagement Solidarity Quality 16 16

17 Tetanos immunization in HIV infected children Only children data (241 pts- 8 studies- 76% retro) 67-90% still protected >2 y 78% still protected >4 y Meta analyse (prosp studies): 74% still protected >2 y, 43% >4 y ccl: probably booster/10 y ok Adult data? 17

18 Duration of TT seroprotection using linear regression in HIV-negative population Estimated half life : 11 years 95% population protected 64 years after vaccination 0.01 IU/ml Log10 (ATA)= α+β*years after vaccination α : log [ATA] at time of immunization β : decay rate [ATA] Hammarlund CID 2016

19 Anti-TT Antibodies persistance after immunization in HIV-infected adults N= 66 T½ (anti-tt Ab decay) 4 years [IC95%, 2,7-7,7] Gobert C et al, unpublished data

20 Yellow Fever Vaccine 20

21 Veit et al. Clin Infect Dis pts < Swiss HIV Cohort Primovaccination after HIV diagnosis - 83% with VL<400 cop/ml - med CD4=536/mm 3 Overall - baseline sero+ 46% (!) - 1 year 95% - 5 years 86% - 10 years 75% VL<400 cop/ml - baseline sero+ 46% (!) - 1 year 99% - 5 years 99% - 10 years 100%

22 First results of CHU Saint-Pierre YF study: preliminary! N= 230 patients Age: med 43 y F 56% HIV mode acq: Ht 75% MSM 19% 7% received YFV before HIV received YFV when HIV+ From SSA 75% 93% >10 y in YF endemic countries: 84% pts/ travel 1 mo (med 3x) 22

23 Immunovirological parameters At time of vaccination - med CD4 564/mm³ - med HIV VL<20 - nadir CD4 230/mm³ But nadir CD4<200: 41% AIDS event in 20% (mostly before YFV) At NT determination -med CD med HIV VL <20 Med time between YFV and Ab determination «delay» : 63 mo (3-455) Med time with ART during delay: 100% 23

24 Results and analysis NT 1/10 80% NT < 10 20% Risk factors for non-protection: -YFV before or after HIV diagnosis p= Age/ Sex/ ethnicity/ HIV acquisition mode p=ns -Med CD4 at time of vaccination p= Cat CD4 at time of vaccination>500 versus <500/mm³ p=ns -Med VL at time of vaccination p= Cat VL at time of vaccination <50 versus >50/ml p=0.02 -Nadir CD4 p= NS -Immunovirological parameters at NT determination p=ns -Time under ART during delay YFV-NT determination p<

25 Plan 1. Mechanisms of defective vaccine response during HIV infection 2. Vaccine schedule : current recommandations and recent data 3. Vertically-infected young adults : a special population

26 Young vertically-infected subjects & vaccine response SIV-model of vertical infection (Xu J Immunol 2018) Profound impact on germinal centers Tfh development Limited B cells expansion & proliferation High rate of (un)structured treatment interruption (Rakhmanina JIAS 2016) CD4+ T cells, Tfh & memory B cells preservation require sustained viral control (Adland AIDS 2018, Muema PLoS One 2017) Meta analysis indicate lower seroconversion rate & antibody persistance What about vertically infected subjects entering adults care?

27 Vertical transmission is a risk factor for measles seronegativity CHU Saint-Pierre Cohort Retrospective study Measles seronegativity in vertically infected subjects 67.7% vs 15.4% (OR 7.7, 95% CI ) Median age : 19 years Majority had 2 doses PENTA Guidelines : Retest Measles serology every 3-5 years Dauby HIV Med 2018

28 High proportion of rubella seronegativity in perinatally-infected women of childbearing age Retrospective study Perinatally-infected women of childbearing age (n=29) Age-matched HIV-infected subjects non-vertical infection (n=58) No difference in Born outside Belgium Sub-Saharan Africa origin VL, CD4 and nadir CD4 Rubella seronegativity (WHO cut off ; 10 IU/ml) 34% (10/29) vs 7,16% (4/58) (p=0.03) Majority of vertically-infected women had received > 1 dose of MMR (median=2) Beum AB et al, manuscript in preparation

29 Conclusions Chronic HIV infection alters B cells, Tfh phenotype & functions compromising GC dynamics that lead to efficient long lived vaccine response Early treatment is critical to preserve those functions Vaccine schedule should be tailored & serological testing considered in : Vertically infected adults Low nadir CD4 count Long duration of uncontrolled VL 29

30 Acknowledgements Pr Corazza C. Nagant Dr Sigi Van Den Wijngaert Funding Association d aide à la recherche médicale André Vésale BREACH Pr De Wit Dr Konopnicki Dr Libois Dr Genotte Dr Martin Dr Gérard Dr Payen Dr S le Dr De Rouffignac Marc Delforge

31 Thank You! Respect Innovation Engagement Solidarity Quality 31