workshop 4: il late-presenter moderatori: g. ippolito, m. moroni discussant: r. iardino limportanza...
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Workshop 4: “Il late-presenter”Moderatori: G. Ippolito, M. MoroniDiscussant: R. Iardino
L’importanza della risposta immunologicaS. Rusconi
“Il late-presenter”:
l’importanza della risposta
immunologicaRoma, preIAS journey - ISS
16 dicembre 2010Stefano Rusconi
DISC L.Sacco, Sezione di Malattie Infettive e ImmunopatologiaUniversità degli Studi di Milano
CD4 count at start of HAART, 2003-2005
Egger M, et al. CROI 2007. Abstract 62.
Data from 42 countries, 176 sites; n=33,008Since 2000, CD4+ cell count at initiation has increased in Sub-Saharan Africafrom 50 to 100 cells/mm3; in developed countries it has remained 150–200 cells/mm3
Numero CD4 alla diagnosi
Prognosis from starting ART according to pre-therapy CD4 cell counts (cells/µL)
ART CC. Egger et al, Lancet. 2002
Prob
abili
ty o
f AID
S 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
CASCADE: Nadir CD4+ Cell Count Predicts AIDS and Non-AIDS Events
Marin B, et al. IAS 2007. Abstract WEPEB019.
1.000.01 1.00 100.00
Nadir CD4+ cell count
AIDS-Related Death
0.01 100.00
200-349 vs ≥ 35050-199 vs ≥ 350
< 50 vs ≥ 350
Non-AIDS–Related Death
1.000.01 100.00
Non-AIDS Cancer Death
1.000.01 100.00
Liver Disease Death
200-349 vs ≥ 35050-199 vs ≥ 350
< 50 vs ≥ 350
200-349 vs ≥ 35050-199 vs ≥ 350
< 50 vs ≥ 350
200-349 vs ≥ 35050-199 vs ≥ 350
< 50 vs ≥ 350
CASCADE Collaboration cohort: N = 9858
Several clinical markers of HIV progression correlated with death due to AIDS-related causes, non-AIDS–related severe infection, liver diseases, and non-AIDS–related malignancies including
– Latest and nadir CD4+ cell counts
– Time spent with CD4+ cell count < 350 cells/mm3
Gras L, et al. J Acquir Immun Defic Syndr. 2007;45:183-192.
CD4
Cell
Coun
t (ce
lls/m
m3 )
0 48 96 144 192 240 288 3660
100
200
300
400
500
600
700
800
900
1000
Week
>500 (n=389)350 – 500 (n=694)
200 – 350 (n=1,513)
50 – 200 (n=1,773)
<50 (n=930)
Baseline CD4(cells/mm3)
50% of those with CD4 nadir <200 fail to reach 500 after 7 years VL suppression.
Suboptimal CD4 T Cell Gains Are Common Among Patients Who Initiate HAART Late (ATHENA)
CNICS: 40% of patients with a nadir CD4 < 200 fail to achieve a normal CD4+ cell count, even after 10 years of
viral suppression (n=300)
Kelley CF, et al. Clin Infect Dis 2009;48:787-794.
0 2 4 6 8 10
100
0
20
40
60
80
<200200-350>350
Nadir CD4
Year of HAART
CD4+
T C
ell >
500
cel
ls/m
m3 (
%)
Influence of Age on CD4 Cell recovery
e la qualità dei CD4…?
C. Negri, S. Rusconi, A. Gori et al. AIDS, Dec. 1996, 10:1737-1738
More MVC Recipients Exceeded Clinically Relevant CD4+ Thresholds in MERIT
85
37
13
75
34
9
0
10
20
30
40
50
60
70
80
90
100
MVC (N = 123)EFV (N = 104)
Perc
enta
ge o
f Pati
ents
≥ 200 Cells/µL ≥ 350 Cells/µL ≥500 Cells/µL
CD4+ Count at Week 96
Patients with Baseline CD4+ Counts < 200 Cells/L
78104 3545 16 9n=
Lazzarin A, et al. HIV10, Glasgow 2010, O422
Conclusion• LPV/r monotherapy failures
occurred in first 24 weeks
• High failure rate was associated
with low nadir CD4+ cell count
(CD4+ <200 cells/mL)
Kaplan-Meier analysis of failure by CD4+ count
Gutman C, et al. 16th CROI, Montreal 2009, #578
0 20 40 60 80
0
20
40
60
80
100
% w
ithou
t fai
lure
CD4+ Nadir <200
CD4+ Nadir >200
weeks
LPV/r monotherapy failures associated with low nadir CD4+ (MOST Study)