Quand débuter les antirétroviraux? Recommandations

Quand débuter les antirétroviraux?
Recommandations internationales
Formation à l’usage des
antirétroviraux
Pr Willy Rozenbaum
When to Start Antiretroviral Therapy
Potential Benefits of Early Therapy
 Earlier suppression of viral replication
 Preservation of immune function
 Prolongation of disease-free survival
 Lower risk of virologic failure?
 Lower risk of detrimental viral evolution
 Possible decrease in the risk of HIV transmission
clinicaloptions.com/hiv
When to Start Antiretroviral Therapy
CD4+ Cell Count Response Based on
Baseline CD4+ Cell Count
Mean CD4+ Cell Count
(cells/mm3)
Johns Hopkins HIV Clinical Cohort
ATHENA National Cohort
1000
1000
800
800
600
600
400
400
BL CD4
> 350
201-350
< 200
200
0
0
1
2
3
Years on HAART
Keruly J, et at. CROI 2006. Abstract 529.
Gras L, et al. CROI 2006. Abstract 530.
4
BL CD4
201-350
> 500
51-200
351-500
< 50
200
0
5
0
48
96
144 192 240
288 336
Weeks From Starting HAART
clinicaloptions.com/hiv
When to Start Antiretroviral Therapy
HAART and Survival Based on Initial
CD4+ Cell Count



Modeled data from ART Cohort
Collaborative
10,855 patients included
934 progressed to AIDS or died
IDUs censored from model
Progression and Death According
to CD4+ Cell Count (cells/mm3)
< 200 vs
201-350
< 350 vs
351-500
Hazard ratio for
AIDS (95% CI)
3.68
(3.01-4.51)
1.52
(1.10-2.10)
Hazard ratio for
AIDS or death
(95% CI)
2.93
(2.41-3.57)
1.26
(0.94-1.68)
Cumulative Probability of AIDS/Death According
to CD4+ Cell Count at Initiation of HAART
0.14
Probability of AIDS or Death

101-200 cells/mm3
201-350 cells/mm3
351-500 cells/mm3
0.12
0.10
0.08
0.06
0.04
0.02
0.00
0
1
2
3
4
5
Years Since Initiation of HAART
D’Arminio Monforte A, et al. CROI 2006. Abstract 525.
clinicaloptions.com/hiv
When to Start Antiretroviral Therapy
Time to Virologic Failure Stratified by
Baseline CD4+ Cell Count
Patients Responding (%)
100
80
60
Baseline CD4+ cell count (cells/mm3)
< 200 (n = 331)
 200 to < 350 (n = 345)
 350 to < 500 (n = 302)
 500 (n = 236)
40
20
0
0
12
24
36
48
60
72
84
96
Time Since Start of Treatment (Weeks)
Levy RS, et al. CROI 2001. Poster 325.
clinicaloptions.com/hiv
When to Start Antiretroviral Therapy
Increasing Prevalence of X4- or R5/X4Tropic Virus at Lower CD4+ Cell Counts
 CCR5
 CXCR4
– With advanced disease, X4- or
dual-tropic virus emerges
– Associated with more rapid
clinical and immunologic
progression
 Could CCR5 inhibition select
for more virulent X4-tropic
virus?
Moyle G, et al. ICAAC 2004. Abstract 1135.
Prevalence of X4 or R5/X4 (%)
– Patients with early-stage HIV
disease tend to have pure R5tropic virus
100
80
60
41.9%
40.0%
51-100
< 50
40
20
16.0%
16.0%
14.8%
0
> 300
201-300 101-200
CD4+ Cell Count (cells/mm3)
n=
248
104
81
31
50
clinicaloptions.com/hiv
Prise en charge médicale des personnes
infectées par le VIH – Rapport 2006
•
Traitement antirétroviral (1)
Quand débuter un traitement antirétroviral ?
Situation
Recommandation
Patients symptomatiques
Initiation le plus rapidement possible, en tenant
(Stades C et B avec symptômes compte du traitement de l’infection opportuniste
marqués)
et des interactions médicamenteuses éventuelles
Patients asymptomatiques avec
CD4 < 200/mm3
Initiation sans délai
Patients asymptomatiques avec
CD4 < 350/mm3
Initiation, sauf si arguments individuels pour
différer
Patients asymptomatiques avec
CD4 > 350/mm3
Initiation habituellement non recommandée,
envisageable dans certaines circonstances
(CV > 100 000 c/ml…)
• L'instauration d'un traitement ARV doit toujours être préparée
– Travail multidisciplinaire pour optimiser l’adhésion au traitement
et aux soins
DHHS Guidelines:
When To Start 2008
Clinical Conditions and/or CD4 Count
Recommendations
History of AIDS-defining Illness
CD4 count <350 cells/mm3
Pregnant women
Persons with HIV-associated nephropathy
Persons coinfected with HBV, when HBV
treatment is indicated
Initiate ARV Therapy
Patients with CD4 > 350 cells/mm3
Optimal time to initiate ARV
therapy not well defined
Consider patient scenarios
and comorbidities