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