Workshop 4: “Il late-presenter”Moderatori: G. Ippolito, M. MoroniDiscussant: R. Iardino
Risposta virologico-clinica e scelta della terapiaC. Mussini
760 pazienti/ 125 morti (16%)
Kaplan Meier plot showing the cumulative proportion of patients with clinical progression, according to the type of
AIDS diagnosis that was present at the time of HIV diagnosis
Prognosis of late presenters
Adapted from Sterne et al. CROI 2009, Abstract 525 and presentation
• Based on 24,444 patients from 15 cohort studies
• 808 deaths and 2366 events in 81,071 person-years of follow-up
0 – 50
51 – 150
151 – 250
0.15
0.10
0.05
0.00
0 1 2 3 4 5 6
Prob
abili
ty o
f dea
th
Years since start of HAART
251 – 350
351 – 450
451 – 550
Years since start of cART
0.40
0.30
0.20
0.10
0.00
0 1 2 3 4 5 6Pr
obab
ility
of A
IDS
or d
eath
EFV vs LPV/RTV in Tx-Naive Pts With CD4+ < 200 in Mexico
HIV-1 RNA < 50 copies/mL at Week 48
Madero JS, et al. IAC 2008. Abstract TUAB0104.
0
20
40
60
80
100
0 16 32 48Week
8 24 40
Efavirenz (n = 95)
LPV/RTV (n = 94)
Number of Pts With HIV-1 RNA < 50 copies/mLEFV 29 70 68 67LPV 8 53 56 50
70.5%
53.2%
0
20
40
60
80
100
HIV
-1 R
NA
< 5
0 co
pie
s/m
L (
%)
79%
49%
64%57%
P = 0.012 P = 0.15
EFV
LPV/RTV
n = 42 45 53 49
≤ 50 cell/mm3 > 50 cell/mm3
EFV met criteria for superiority to LPV/RTV: Δ 17% (CI 95%: 3.5% to 31.0%; P = .017)
HIV
-1 R
NA
< 5
0 co
pie
s/m
L (
%)
By BL CD4+ Cell Count
STARTMRK: Virologic and Immunologic Efficacy at Week 48
Significantly shorter time to virologic response with RAL vs EFV (P < .001)
Significantly greater CD4+ cell count increase with RAL vs EFV
+189 vs +163 cells/mm3; Δ: 26 cells/mm3 (95% CI: 4-47)
Lennox J, et al. ICAAC/IDSA 2008. Abstract 896a. Adapted with permission of Merck & Co., Inc., Whitehouse Station, New Jersey, USA. Copyright © 2008 Merck & Co., Inc., Whitehouse Station, NJ, USA. All rights reserved.
0
20
40
60
80
100
0 16 32 48Weeks
Pat
ien
ts W
ith
HIV
-1
RN
A <
50
cop
ies/
mL
(%
)
2 4 8 12 24 40
86%
82%
RAL n = 281 279 281 279 281 279 278 280 280EFV n = 282 282 282 282 281 282 280 281 281
Δ: 4% (95% CI: -2 to 10)P < .001 for noninferiority
RAL
EFV
ITT, NC = F
Incidence of PcP if CD4 ≤ 200
VL Prophylaxis
Person-years of
follow-up events Incidence/1000y
(95% CI)
<400 no 1944 7 3.6 (1.4-7.3)
<400 yes 4444 12 2.7 (1.4-4.7)
400-9999 no 657 9 13.7 (6.3-26.1)
400-9999 yes 976 8 8.2 (3.5-16.2)
>10000 no 2046 106 51.8 (41.9-61.6)
>10000 yes 1789 39 21.8 (15-28.6)
Incidence of secondary PcPIn
cid
enc
e s
eco
nd
ary
PC
P p
er 1
000
PY
FU
(95%
CI)
0.1
1
10
100
1000
Proph
Events
No
1
No
1
No
4
Yes
5
Yes
1
Yes
2
No
5
No
0*
No
0*
Yes
2
Yes
0*
Yes
0*
CD4 < 200 CD4 > 200
<400 400-9999 >10000 <400 400-9999 >10000
*No events; incidence and lower bound of 95% CI=0.0
Pro
po
rzio
ne
co
n
Dis
turb
i N
P
Prevalenza di HAND in epoca post-HAARTPrevalenza di HAND in epoca post-HAART(Studio CHARTER)(Studio CHARTER)
15.1%
25.4%17.7%
4.8%
18.3%28.3%
26.5%
0.5%
1.9%1.8%
0%
10%
20%
30%
40%
50%
60%
HIV- CDC A CDC B CDC C
ANI MND HAD
(n=212) (n=437) (n=213) (n=113)
Letendre et al., 2007
Updated CSF Penetration Effectiveness Scores Overall CPE score = sum of following scores for the
individual agents
Classification Score Agents
Good penetrators 4 IDV/RTV, NVP, ZDV
Decent penetrators 3 ABC, DLV, DRV/RTV, EFV, FPV/RTV, FTC, IDV, LPV/RTV, MVC,
RAL
Limited penetrators 2 3TC, ATV ± RTV, d4T, ddI, ETR, FPV
Poor penetrators 1 ddC, ENF, NFV, RTV, SQV ± RTV, TDF, TPV
Letendre S, et al. CROI 2010. Abstract 172.
MONOI: 48 Wk Outcomes With DRV/RTV Monotherapy vs Triple Therapy DRV/RTV monotherapy met criteria for
noninferior virologic efficacy vs DRV/RTV + 2 NRTIs at Wk 48 in PP analysis, but not in ITT-E analysis
– PP population = all pts from ITT population except pts who d/c tx without virologic failure or SAE (n = 10) or pts withdrawn without virologic failure or SAE (n = 6)
Virologic failure in 3 pts (2.7%) on monotherapy vs 0 on standard therapy
– Low DRV drug levels noted in 1 pt
– No DRV RAMs in any pt with virologic failure
– All 3 pts regained HIV-1 RNA < 50 c/mL on reintroduction of 2 NRTIs
Virologic Response at Wk 48, %*
DRV/RTV
DRV/RTV+ 2 NRTIs
Δ Lower Limit of 90% CI
PP analysis (n = 204)
94.1 99.0 -4.9 -9.0
ITT-E analysis (n = 225)
87.5 92.0 -4.5 -11.0
Viremia detected in CSF in 2 of 3 pts with serious CNS disorders on monotherapy arm
– Each pt had HIV-1 RNA < 200 c/mL in CSF following reintroduction of NRTIs
Katlama C, et al. IAS 2009. Abstract WELBB102.
Virologic failure defined as consecutive HIV-1 RNA > 400 c/mL or treatment modification or discontinuation
CONCLUSIONI
La sopravvivenza del paziente libero da malattia deve essere l’obiettivo della TARV.
Il successo virologico costituisce un fattore essenziale per la prognosi a lungo termine.
La prescrizione di un regime terapeutico deve tener conto anche della penetrazione nei diversi comparti.
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