Late presentation in European

countries

30th January 2019, Bucharest

30-31 January 2019,

Bucharest - Lundgren

Quality of HIV-Care and Management – Benchmarking and Regional Differences across Europe

Kamilla Grønborg Laut, MD

Late-presentation in European countries

Prof Jens Lundgren

CHIP, Rigshospitalet, University of Copenhagen

WHO Collaborative Centre on HIV, viral hepatitis and TB

@ProfJLundgren

Tracking late presentation (LP):

why and how

• Conceptually: Delayed access to health-care services (as opposed to timely)

– Concept is driven by the evolving state-of-the-art evidence of what is optimal care

• Hence, vision for optimal provision of health services = none of newcomers accessing care are late presenters

• However

– Case definitions for LP not optimal

– Health systems are not always able to capture relevant data

2014/15

Country-specific estimates of people on ART and virologically suppressed

Pro

po

rtio

n v

iro

logi

cally

su

pp

ress

ed a

mo

ng

tho

se o

n A

RT

(%)

Western Europe

Southern Europe

Northern Europe

East Central Europe

Eastern Europe

-10

0

10

20

30

40

50

60

70

80

90

100

-10 0 10 20 30 40 50 60 70 80 90 100

West

South

North

East Central

East

Pe

rce

nta

ge v

iro

logi

cally

su

pp

ress

ed a

mo

ng

tho

se o

n A

RT

(%)

Percentage on ART among those in care (%)

Suppressed = <500copies/mL

Bubble size, number of people:

100

1000

EuroSIDA: Laut et al, Eurosurveillance 2018

Late presentation: < 350 CD4´s or an AIDS event Advanced HIV disease: A late presenter with < 200 CD4´s

> 350 CD4´s (60%)

A consensus definition of “late presentation”

< 350 CD4´s (40%)

HIV Medicine, 2011

Adjusted odds of having no CD4 count information in 6 months

following HIV diagnosis : COHERE 2010-2013

Adjusted odds (95% CI)

0,5 5

Date HIV test / year later

Age / 10 years older

Region of origin

European region of care

HIV exposure group

Unknown Other Africa Europe

East North Central South

Female other

Male other

Female IDU

Male IDU

Female heterosexual

Male Heterosexual

MSM

MSM; males having sex with males. IDU; intravenous drug user

Adjusted odds ratio (95% confidence interval)

2 3 4

Mocroft et al, Eurosurveillance 2015

Changes over time in late presentation COHERE 2010-2013 :

A comparison of HIV exposure groups

0

10

20

30

40

50

60

70

MSM M Het F Het M/F IDU M/F Other

2010 2011 2012 >=2013Calendar year of

Late presentation: diagnosed with HIV with a CD4 count below 350/mm3 or an AIDS defining event regardless of the CD4 count, in the 6 months following HIV diagnosis. MSM; males having sex with males. M; male. F; female. Het; heterosexual. IDU; intravenous drug user. *Adjusted for

age, European region of care, region of origin, delayed access to care

HIV Exposure group

Per

cen

tage

wit

h L

P

Odds of late presentation : Per year later of presentation Univariate 0.99 (0.96 – 1.03) 0.99 (0.93 – 1.05) 1.04 (0.98 – 1.09) 1.16 (1.03 – 1.31) 1.10 (1.02 – 1.17) Multivariate* 0.98 (0.95 – 1.01) 0.97 (0.91 – 1.03) 0.99 (0.93 – 1.05) 1.16 (1.02 – 1.32) 1.08 (1.00 – 1.16)

Mocroft et al, Eurosurveillance 2015

Mis-classification

• In early HIV infection, transient low CD4 count, fairly

common

• As recent infection becomes progressively larger % of

diagnosed population, more of those classified as LP are

actually recently infected.

• E.g., in 7949 PLWH, diagnosed in Belgium 1998-2012 (Sasse et al, HIV Med, 2016)

30-31 January 2019,

Bucharest

MSM Heterosexual

Weighing simplicity, versus

–Ability to reliable capture

recent infection

30-31 January 2019,

Bucharest

Technical aspects of the definition of “late presentation”

It is recommended to measure CD4´s twice. If done

both should be below 350

Pay attention to conditions associated with transient

artificially low CD4 counts such as pregnancy,

concomitant infections, recent infection, or

myelosuppressive therapy

Antinori et al, HIV Medicine, 2011

Definition of late presentation and indication to start

ART

• CD4 treshold was aligned when consensus definition of

late presentation was developed in 2009-2010

• But not any longer

30-31 January 2019,

Bucharest

Policies on ART initiation in European countries 2014 (n=49), 2016 (n=47), 2018 (n=52)

2015

4

29

46

16

10

5

28

8

1

1

0

5

10

15

20

25

30

35

40

45

50

55

2014 2015 2016 2018

Nu

mb

er o

f co

un

trie

s/A

RT

po

licy

200 cells/mm3

350 cells/mm3

500 cells/mm3

Source: ECDC. Dublin Declaration monitoring 2018; validated unpublished data.

Definition of late presentation and indication to start

ART

• CD4 treshold was aligned when consensus definition of

late presentation was developed in 2009-2010

• But not any longer

• Does this make ”late presentation” research and public

health surveillance obsolete ?

– Is any newly infected patient not presenting for care a

“late presenter” ?

30-31 January 2019,

Bucharest

30-31 January 2019,

Bucharest

West Central East

Total diagnosed HIV-positive 2010-2015*

134250 18306 497603

Clinical event

rate/100

PYFU**

Non-LP (95% CI) 0.43

(0.33 – 0.54)

0

(0 – 3.73)

0

(0 – 3.40)

LP (95% CI) 5.15

(4.79 – 5.52)

6.38

(3.19 - 11.42)

3.89

(1.06 – 9.96)

Using COHERE/

EuroSIDA

data

LP (95% CI) 48.4

(47.9 – 48.9)

64.0

(58.4 – 69.7)

49.1

(42.4 – 55.7)

Estimated number LP (upper-lower bound)

64941 (64271 – 65611)

11721 (10688 – 12754)

244236 (211214 – 277259)

Estimated excess event rate* (upper-lower bound)

2407 (3.7%) (2275 – 2539)

710 (6.1%) (355 – 1038)

8933 (3.7%) (2434 – 14771)

Estimate of regional burden of LP and excess clinical events

attributable to LP within 1 year from diagnosis:

2010-15 in selected countries across Europe

Laut on behalf of the late presentation working groups in the COHERE and EuroSIDA studies

N= 39,007

West: Belgium, UK, Spain, Netherlands, Greece, Austria, France, Italy, Denmark, Switzerland, Sweden, Germany. Central †: Poland. Bulgaria included in regional estimates only. East †: Estonia, Russia. †Based on EuroSIDA data only.

3.7%

Immigration

• LP population in a given region/country dominated by

recent immigrants

• Do not have direct implication for testing policies in the

region/country

30-31 January 2019,

Bucharest

16

Proportion HIV diagnoses in migrants* by country of report and region of origin,

EU/EEA 2017

Source: ECDC/WHO (2018). HIV/AIDS Surveillance in Europe 2018– 2017 data

EU/EEA: 41% diagnosed in 2017 were born abroad

Central and Eastern Europe

* Migrants include all persons born outside of the country in which the diagnosis was made.

Sub-Saharan Africa

Western Europe

Latin American and Caribbean

South and Southeast Asia

Other

Data include only cases with known region of origin; No data were reported by Germany in 2017 and zero cases were reported among migrants in Hungary or Liechtenstein

17

Proportion of persons diagnosed late* with HIV by demographic, EU/EEA, 2017

Age group (years) Transmission Region of origin Gender

*Diagnosed late=CD4<350 cells/mm3 at diagnosis

Source: ECDC/WHO (2018). HIV/AIDS Surveillance in Europe 2018– 2017 data

18

Proportion of HIV cases diagnosed late, 2017, EU/EEA

% persons with CD4 <350 cells/mm3 at HIV diagnosis

• EU/EEA average: 49%

Non-visible countries

Source: ECDC/WHO (2018). HIV/AIDS Surveillance in Europe 2018– 2017 data

Weighted estimates of LP using TESSy

data as reference population.

04/02/2019

0

50

100

Per

cen

tage

late

pre

sen

ters

(95%

CI)

Data from COHERE/EuroSIDA Weighted data

Laut on behalf of the late presentation working groups in the COHERE and EuroSIDA studies

Principle public health reaction to LP surveillance

30-31 January 2019,

Bucharest

Total number of LP cases

Low Moderate High

% of diagnosed being LP

Low

Moderate

High

Testing policies working reasonable

Testing policies needs revision

Testing policies not working as intended

04/02/2019 BMC Medcine 2017

Summary

Late presentation is associated with increased patient morbidity and mortality, healthcare costs and risk of onward transmission by individuals unaware of their status

4-6% of late presenters experience excess serious disease/dies

Limits the effectiveness of all subsequent steps in the cascade of HIV care

Definition is imperfect – results needs analysis and interpretation

Many countries unable to provide data to ECDC/WHO-E

Strengthen collaboration between surveillance and clinic cohort

Modest/no improvement in last decade

=

Room for improvement of testing strategies

30-31 January 2019,

Bucharest

Acknowledgements

• Late-presenter team from EuroSIDA/COHERE: Amanda Mocroft, Kamilla Laut, et al

• ECDC: Teymur Noori, Anastasia Pharris, Andrew Amato, et al

• WHO-Europe: Masoud Dara; Elena Vovc, Annemarie Stengaard

• Dedicated colleagues across the continent working hard to prevent HIV transmission and improve health in their setting

• CHIP: Dorthe Raben, Alvaro Borges, Anne Raahauge, et al

Figure 2

Changes over time in late presentation and CD4 count at

HIV-diagnosis : COHERE 2010-2013

Late presentation: diagnosed with HIV with a CD4 count below 350/mm3 or an AIDS defining event regardless of the CD4 count, in the 6 months following HIV diagnosis. Late presentation with advanced disease: diagnosed with HIV with a CD4 count below 200/mm3or an AIDS defining event, regardless of CD4 cell count, in the 6 months following HIV diagnosis. Late presentation with very advanced disease: diagnosed with HIV with a CD4 count below 50/mm3or an AIDS defining event, regardless of CD4 cell count, in the 6 months following HIV diagnosis

0

20

40

60

2010 2011 2012 2013

Late Presentation

Late presentation with advanced disease

N 10766 10054 6259 3375 Year of diagnosis

Perc

enta

ge

Med

ian

CD

4 a

t H

IV d

iagn

osi

s (I

nte

rqu

arti

le r

ange

)

0

100

200

300

400

500

600

Mocroft et al, Eurosurveillance 2015

Figure 3b

Changes over time in late presentation COHERE 2010-

2013:

A comparison of European region of care

0

10

20

30

40

50

60

70

South Central North East+

2010 2011Calendar year of

Late presentation: diagnosed with HIV with a CD4 count below 350/mm3 or an AIDS defining event regardless of the CD4 count, in the 6 months following HIV diagnosis. MSM; males having sex with males. M; male. F; female. Het; heterosexual. IDU; intravenous drug user. *Adjusted for

age, HIV exposure group, region of origin, delayed access to care. +No data from 2013

European region of care

Per

cen

tage

wit

h L

P

Odds of late presentation : Per year later of presentation Univariate 1.04 (1.00 – 1.07) 1.01 (0.97 – 1.05) 0.93 (0.89 – 0.97) 1.12 (0.97 – 1.31) Multivariate* 1.02 (0.99 – 1.06) 1.04 (1.00 – 1.09) 0.89 (0.85 – 0.94) 1.05 (0.90 – 1.23)

Mocroft et al, Eurosurveillance 2015