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)