Quand débuter les antirétroviraux? Recommandations internationales
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Quand débuter les antirétroviraux?Recommandations internationales
Formation à l’usage des antirétroviraux
Pr Willy Rozenbaum
clinicaloptions.com/hiv
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
Keruly J, et at. CROI 2006. Abstract 529. Gras L, et al. CROI 2006. Abstract 530.
0 48 96 144 192 240 288 336
Years on HAART
ATHENA National CohortJohns Hopkins HIV Clinical Cohort
Mea
n C
D4
+ C
ell
Co
un
t (c
ells
/mm
3)
200
400
600
800
00
1 2 3 4 5
Weeks From Starting HAART
1000
200
400
600
800
0
1000
> 500351-500
201-35051-200
< 50
BL CD4> 350
< 200201-350
BL CD4
clinicaloptions.com/hiv
When to Start Antiretroviral Therapy
101-200 cells/mm3
201-350 cells/mm3
351-500 cells/mm3
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
D’Arminio Monforte A, et al. CROI 2006. Abstract 525.
Cumulative Probability of AIDS/Death According to CD4+ Cell Count at Initiation of HAART
Years Since Initiation of HAART
0 1 2 3 4 50.00
0.02
0.04
0.06
0.08
0.10
0.12
Pro
ba
bil
ity
of
AID
S o
r D
ea
th
0.14
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)
clinicaloptions.com/hiv
When to Start Antiretroviral Therapy
Time to Virologic Failure Stratified by Baseline CD4+ Cell Count
Levy RS, et al. CROI 2001. Poster 325.
0
20
40
60
80
100
0 12 24 36 48 60 72 84 96
Pat
ien
ts R
esp
on
din
g (
%)
Time Since Start of Treatment (Weeks)
Baseline CD4+ cell count (cells/mm3)
< 200 (n = 331) 200 to < 350 (n = 345) 350 to < 500 (n = 302) 500 (n = 236)
clinicaloptions.com/hiv
When to Start Antiretroviral Therapy
Increasing Prevalence of X4- or R5/X4-Tropic Virus at Lower CD4+ Cell Counts CCR5
– Patients with early-stage HIV disease tend to have pure R5-tropic virus
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?
16.0% 16.0% 14.8%
41.9% 40.0%
0
20
40
60
80
> 300
248
Pre
vale
nce
of
X4
or
R5/
X4
(%)
100
201-300
104
101-200
81
51-100
31
< 50
50
CD4+ Cell Count (cells/mm3)
n =
Moyle G, et al. ICAAC 2004. Abstract 1135.
Prise en charge médicale des personnes infectées par le VIH – Rapport 2006
Traitement antirétroviral (1)
Prise en charge médicale des personnes infectées par le VIH – Rapport 2006
Traitement antirétroviral (1)• Quand débuter un traitement antirétroviral ?
Situation Recommandation
Patients symptomatiques (Stades C et B avec symptômes marqués)
Initiation le plus rapidement possible, en tenant compte du traitement de l’infection opportuniste 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 2008DHHS 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