Pulido, J. R. Arribas , B. Clotet , J. M. Gatell , J. A. Iribarren ,
A consensus definition of “late presentation” Jose M Gatell.
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Transcript of A consensus definition of “late presentation” Jose M Gatell.
A consensus definition of “late presentation”
Jose M Gatell
A consensus definition of “late presentation”
1. The need2. The outcome3. The rationale4. The process5. The implementation and its
consequences6. How to keep it updated
A consensus definition of “late presentation”
1. The need
A concept frequently used and applied for a wide range of purposes
Substantial variability
Consensus that “the later” the worse for individuals and for public health and also more costly
Late presentation in Europe
Many definitions reportedTime until first ADE Country and year
< 1 year European survey, 2006
< 6 months England, 2006France, 1998Italy, 2005
< 3 months Sweden, 2005England, 2000France, 2004, 2007Italy, 2000Poland, 2006
< 8 weeks Spain, 2002Denmark, 2005
< 1 month England, 2001Italy, 2003
Concurrent AIDS Poland, 2006England, 2006France, 2000
Adler et al. AIDS Care 2008:1
Summary of definitions used in trials identified in a
literature search carried out in 2007
CD4 count Country and year
CD4 < 350 England, 2000
CD4 < 200 UK 2000, 2005, 2006
France 2006, 2007
Italy, 2004
CD4 < 50
Spain, 2005
UK 2004
Late presentation in Europe
Effect of choice of definition
26.7%
20.0%
Basis of definition:AIDS CD4Both
15.0%
14.0%
16.0%
14.1%
8.9%
30.0%
31.0%34.0%
• New patients presenting late (%)
• Survey carried out in September 2007
38.0%
• Belarus, Estonia, Moldova, Portugal, Slovakia, and Slovenia did not report prevalence
• Belgium, Cyprus, Finland, Ireland, Latvia, Lithuania, Luxemburg, Romania, Sweden did not respond to survey
Adler et al. AIDS Care 2008:1
Late presentation in Europe
BHIVA audit: scenario leading to death
Adapted from Lucas. Clin Med 2008;8:250
6.5
2.1
0
0.3
0.3
1.8
2.8
3.4
4.7
6.7
15.8
24
31.8
0 10 20 30 40
Not known/not stated
Other
Treatment delayed/ineligible for NHS
Died in community without seeking care
Unable to take treatment – toxicity/intolerance
Successful treatment but suffered catastrophic event
MDR HIV, run out of options
HIV +ve, irregular care, re-presented too late
Chose not to receive treatment
Treatment ineffective due to poor adherence
Under care but had untreatable complication
Diagnosed too late for effective treatment
Death not directly related to HIV
Percentage of deaths
n = 387 deaths between October 2004 and September 2005
Inci
denc
e pe
r 10
00 P
YF
U (
95%
CI)
Current CD4 count (/mm3)
AIDS defining illnessNon-AIDS defining illness
<50 51-100 101-200 201-350 351-500 501-700 >700
Incidence of AIDS-defining & Non-AIDS defining illness and current CD4 count
1
10
100
1000
EuroSIDA: Mocroft et al, CROI 2009
AIDS defining illnessNon-AIDS defining illness
Prognosis from starting ART according to pre-therapy CD4 cell counts and HIV-RNA levels
ART CC. Egger et al, Lancet. 2002
CD4 Cell Count (cells/µL)P
rob
abili
ty o
f A
IDS
or
Dea
th (
%)
Years From Starting ART
0-49
50-99
>350
100-199
200-349
0 1 2 30
5
10
15
20
25
Deirdre et al JID, 2008
Late presentation in Europe
Cost of late presentation in Canada
• Based on data from 241 patients
• Estimated excess cost of late presentation, after adjusting for patient characteristics: CAN$9,723
• Difference in total costs largely attributable to differences in HIV-related hospital care costs (15 times higher for late presenters)
18488
8455
0
4000
8000
12000
16000
20000
Latepresenters
Non-latepresentersM
ea
n a
nn
ua
l c
os
ts, y
ea
r a
fte
r d
iag
no
sis
(C
AN
$)
Adapted from Krentz et al. HIV Med 2004;5:93CD
4 co
un
t <
200
cel
ls/m
l at
pre
sen
tati
on
A consensus definition of “late presentation”
1. The need2. The outcome3. The rationale4. The process5. The implementation and its
consequences6. How to keep it updated
A consensus definition of “late presentation”
2. The outcome…
Is a definition intended (and hopefully valid) for identifying patients at particularly raised risk of clinical disease progression, improving surveillance and for satisfying public health needs.
Responds to the need of a common European definition for late presentation
2. The outcome…
Late presentation: < 350 CD4´s or an AIDS event
Advanced HIV disease: A late presenter with < 200 CD4´s or an AIDS event
> 350 CD4´s (50%)
A consensus definition of “late presentation”
< 350 CD4´s (50%)
2. The outcome…
Late presentation: < 350 CD4´s or an AIDS event
Advanced HIV disease: A late presenter with < 200 CD4´s
A consensus 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, or myelosuppressive therapy
2. The outcome… (from earlier group discussion)
Late presentation: < 350 CD4´s or an AIDS event
Advanced HIV disease: A late presenter with < 200 CD4´s
A consensus definition of “late presentation”
Presentation is different than diagnosis
Presentation to a facility able to monitor the evolution of infection and to prescribe treatment if considered necessary
CD4 levels for naive patients (approximately 300 per year)
0
10
20
30
40
50
60
70
80
90
100
1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007
Year
%
>350
250-350
<200
Late presentation in Europe
Late presentation in Italy
0
200
400
600
800
1992-1996 1997-2001 2002-2006
CD
4 c
ou
nt
(ce
lls
/mm
3)
85th percentile
75th percentile
50th percentile
25th percentile
15th percentile
Estimated adjusted CD4+ cell count percentiles at HIV diagnosis in Modena (Italy) between 1992 and 2006. Estimates were obtained by fitting a simultaneous quantile regression model for the percentiles in the graph, adjusted for: sex, age at diagnosis, country of birth, exposure category, and years of diagnosis.
Despite improvements in diagnosis and treatment, > 25% of patients still present with CD4 < 200/μL and > 50% with < 350
Adapted from Borghi et al. J Acquir Immune Defic Syndr 2008;49:282Lat
e p
rese
nte
rs h
ad C
D4
< 2
00 c
ells
/μL
or
AID
S w
ith
in 3
mo
nth
s
A consensus definition of “late presentation”
1. The need2. The outcome3. The rationale4. The process5. The implementations and its
consequences6. How to keep it updated
Inci
denc
e pe
r 10
00 P
YF
U (
95%
CI)
Current CD4 count (/mm3)
AIDS defining illnessNon-AIDS defining illness
<50 51-100 101-200 201-350 351-500 501-700 >700
Incidence of AIDS-defining & Non-AIDS defining illness and current CD4 count
1
10
100
1000
EuroSIDA: Mocroft et al, CROI 2009
AIDS defining illnessNon-AIDS defining illness
Lancet 2009
HIV-1 infected adults with CD4 cell count > 500/mm3 on long-term ARV therapy reach same
mortality rates as the general population
• Standardized mortality ratio (SMR) in 2435 HIV-infected adults, according to cumulated time spent with CD4 cell count between 350 and 499 /mm3 and > 500 /mm3, after the time of truncation $
Lewden C, Chêne G, Morlat P, Raffi F, Dupon M, Dellamonica P, et al. JAIDS 2007, Sept.
SMR(CI)
8
7
6
5
4
3
2
1
00 1 2 3 4 5 6 7 8
Time of truncation after initiation of cART (years)
§ truncation : the time period taken into account starts 1, 2, 3, … years after initiation of cART
CD4 : 350 to 499/mm3
CD4 > 500/mm3
ANRS CO8 APROCO-COPILOTE and ANRS CO3 AQUITAINE cohorts, 1997-2005
Gras et al.
CD4+ T cells/mm3 at
baseline*
CD4+ T cells/mm3 at last determination*
Total <200 200-349 350-499 >=500
<200 91 (31) 94 (32) 62 (21) 48 (16) 295
200-349 15
(8.5)28 (16) 39 (22) 94 (53.5) 176
350-499 2 (2) 4 (3) 21 (19) 85 (76) 112
>=500 0 (0) 2 (4) 5 (9) 47 (87) 54
Total 108 (17)
128 (20) 127 (20) 274 (43) 637
Classification of the patients according to baseline and last determination of CD4+ T cells after a median f/u 3 years
*Number of patients (%); García F, et al. J AIDS. 2004. *Number of patients (%); García F, et al. J AIDS. 2004.
A consensus definition of “late presentation”
1. The need2. The outcome3. The rationale4. The process5. The implementation and its
consequences6. How to keep it updated
A consensus definition of “late presentation”
4. The process…. Initiated by
involved clinicians, patient group representatives, public health workers and other stakeholders in the field of HIV
A consensus definition of “late presentation”
1. The need2. The outcome3. The rationale4. The process5. The implementation and its
consequences6. How to keep it updated
A consensus definition of “late presentation”
5. The implementations and its consequences
- Make the problem “visible”- Be used to report surveillance data and
compare between countries- Identify risk factors in a common way- Be used to monitor the evolution by
official bodies or academic organizations (COHERE: 31 cohorts from 10 European countries)
- Quality control marker for public health policies and academic initiatives (like “HIV in Europe”) promoting earlier diagnosis
A consensus definition of “late presentation”
5. The implementation and its consequences (from eralier group discussion)
- Publication of a brief position paper focusing exclusively on the definition, the rational behind it and tis potential consequences apart from a general report of the whole meeting
- Make it available to editors of main journals and suggest they request authors of papers on “late presentation” to perform and report at least a subanalysis using the definition
Late presentation in Europe
Who is likely to present late?
• Heterosexuals• Older patients• Migrants
• Intravenous drug users are– Less likely to be diagnosed late– More likely to experience a delay in presenting for clinical care
once diagnosed– More likely to be lost to follow-up
This slide represents the expert opinion of the Scientific Committee (Yazdan Yazdanpanah, Joep Lange and Jan Gerstoft), March 2009
A consensus definition of “late presentation”
1. The need2. The outcome3. The rationale4. The process5. The consequences6. How to keep it updated
A consensus definition of “late presentation”
6. How to keep it updated
The definition mainly reflect most common current recommendations on when to start cART. If guidelines change the definition will be reviewed and may also change (although not automatically)