Bases de données observationnelles AC12

Bilan 2007 et Objectifs 2008

Le modèle originel :Antiretroviral Therapy (ART)Cohort Collaboration

• France• French Hospital Database on HIV (FHDH)• Aquitaine Cohort

• Germany• Frankfurt HIV Cohort • Köln / Bonn Cohort

• Italy• Italian Cohort of Antiretroviral-Naive Patients (ICONA)

• Switzerland• Swiss HIV Cohort Study

• Netherlands• AIDS Therapy Evaluation project Netherlands (ATHENA)

• Spain• PISCIS, Catalonia and Balearic islands

• United Kingdom• Royal Free Hospital Cohort, London

• The Multicenter Study Group on EuroSIDA• 29 European countries

• Canada• British Columbia Centre for Excellence in HIV (BCCfE-HIV)• South Alberta Clinic

• USA• Collaborations in HIV Outcomes Research US (CHORUS)• 1917 Clinic Cohort, University of Alabama, Birmingham • University of Washington HIV Cohort, Seattle• Veterans Aging Cohort Study (VACS), West Haven

www.art-cohort-collaboration.org

ARTCohort Collaboration

The Antiretroviral Therapy in Low-Income Countries (ART-LINC) Collaboration

ANRS 12101 / 12138 & NIH/OARDabis, Egger, Schechter

• A network of 21 HIV treatment programs and 47 clinical centers in Africa (Morocco, Senegal, Côte d’Ivoire, Nigeria, Cameroon, Uganda, Malawi, South Africa, Botswana), Latin America (Argentina, Brazil), and Asia (India, Thailand)

– Sites identified through literature searches and personal contacts• Site assessments conducted through self-administered surveys and on-site

assessments by ART-LINC central team (2004 and 2006) and through an electronic system DataCol ® (2008)

– Pooling of existing databases with individual patient data:• Merger # 1 : 2004-2005, N = 8.700

• Merger # 2 : 2006-2007, N = 40,000

Number of patients receiving ART (A); Proportion of women (B);Median baseline CD4 (C); Proportion with viral load (D) - Kaiser (CROI 2008)

Mortality over four years

Sub-Saharan Africa

Europe & North America

Months after start of ART

0 12 24 36 48

Cum

ulat

ive

mor

talit

y (%

)

0

5

10

15

CROI 2007 – Egger Plenary

Sustained long‑term CD4 response to ART among naïve patients in low‑income countries

Denis Nash - CROI 2008

114

263

230

395366377376372

355336

301

0

50

100

150

200

250

300

350

400

450

Baseline 1 2 3 4 5

Sustained long‑term CD4 response to ART among naïve patients in low‑income countries

D. Nash - CROI 2008Most important determinant of CD4 trajectory after ART initiation is

baseline CD4 (increasing with calendar time at most sites)

0

100

200

300

400

500

600

700

Baseline 1 2 3 4 5

Missing0-<2425-4950-99100-149150-199200-299300+

Higher incidence in lower-income countries(7.4 vs 1.0 per 100 PY) but relative reduction over time is comparable and low CD4 is the most important risk factor

QuickTime™ et undécompresseur TIFF (non compressé)

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Tuberculosis in the first year after Initiation of ART in Low-Income and High-Income CountriesThe ART-LINC Collaboration and The ART Cohort Collaboration

CID 2007:45 (1 December)

Probability of death or lost-to-follow-up in 2,710 adults starting ART at WHO stage 1 or 2 and CD4 >200/mm3 or unknown,

according to CTX prescription (C. Lewden in progress)

CTX+HAART Only HAART

De

ath

or

loss

to fo

llow

-up

pro

ba

bili

ty

0.00

0.04

0.08

0.12

0.16

0.20

Time (months)

0 6 12 18 24

P=0.006

Adjusted HR: 046 (0.30-0.73)

Coût-efficacité de stratégies de rétention des patients sous ART

Hapsatou Touré, Xavier Anglaret, Elena LosinaFrançois Dabis, Ken Freedberg

Objectif général

Comparer l’efficacité et les ratios de coût/efficacité de stratégies actives de recherche de patients, initialement sous traitement antirétroviral, perdus de vue dans des cohortes sélectionnées de pays à ressources limitées (Abidjan, Cape Town, …)

ART-LINC: Box 5, P. 28-29

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International epidemiological Databases to Evaluate AIDS

• 7 regional networks• North America• South America / Caribbean• West Africa• Central Africa• East Africa• Southern Africa• Australia / Asia

• Resource limited countries networks• ART-LINC Collaboration• Treat Asia HIV Observational Database (TAHOD)

www.iedea-hiv.orgwww.art-linc.orgwww.amfar.org

International epidemiological Database to Evaluate AIDS (IeDEA)

IeDEA – West AfricaCoordinating Investigators

François DABIS (France)Emmanuel BISSAGNENE (Côte d’Ivoire)

Project ManagerDidier K. EKOUEVI

Progress report - February 2008

Adult clinical centers in West Africa (N = 16,945)Name Location Number of patients on HAART

USAC Côte d’Ivoire 2442

CePReF Côte d’Ivoire 3393

MTCT-Plus Côte d’Ivoire 461

SMIT Côte d’Ivoire 4608

CIRBA Côte d’Ivoire 2272

CNTS Côte d’Ivoire 716

Toure Hospital Mali 1113

Point G Mali 431

CNHU Benin 872

ANRS 1215 Senegal 404

MRC Gambia 233

Death probability in the first 12 months after ART initiation for 11 adult cohorts in West Africa

according to baseline CD4 count (N = 14,832)

9.4%

2.1%

4.6%

Retention of the patients in the 11 participating adult clinics in West Africa in the first 12 months

after ART initiation (N = 14,832 adults)

81.0%[81.3-82.6]

International epidemiological Database to evaluate AIDS (IeDEA) in West Africa

Cancer research proposal #1 - 2008

Prevalence of tobacco, alcohol and other recreational drugs use within HIV-infected

adult cohorts

International epidemiological Database to evaluate AIDS (IeDEA) in West Africa

Cancer research proposal #2 - 2008

HIV prevalence among patients hospitalized for malignancy in Abidjan (Côte d’Ivoire)

Paediatric ART in Sub-Saharan Africa:the multi-center KIDS-ART-LINC collaboration

Dabis, Mbori-NgachaANRS 12147 & NIH/OAR

To define prognosis of children treated with ART in sub-Saharan Africa in relation to the

type of treatment program

http://www.rcqhc.org/kids-art-linc

Scientific Output 2006-2007

• Site assessment and organization of collaboration published in Cohort Profile section of Int J Epidemiol 2007;doi:10.1093/ije/dym216

• First data merger completed (individual clinical data from 8 sites, 3644 children, 2.666 on ART)

• Two-year survival analysis done and results presented

o CROI 2007 (Los Angeles) – February 2007

o PEPFAR 2007 (Kigali) – June 2007

o Manuscript submitted

Delay in start ART until immunodeficiency results in excess mortality, most in 1st six months treatmentArrive CROI 2007 (cité par Mofenson - CROI 2008)

Months from ART start Probability of death after starting ART

Immune Deficient at Start ART

Not Immune Deficient at Start ART

6 months7.8% 1.8%

12 months 8.2% 2.2%

Meta-analysis 1,195 children from 8 African data bases53% >5 years of age, 66% severe age-related immune deficiency

ARV: NNRTI-based 58%, PI-based 37%

6% excess mortality0.4%after 6 mos

0.4%after 6 mos

KIDS-ART-LINC: Box 3, P. 24-25

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Scientific perspectives 2008

• More analyses of the first merger :

– Sustained response to first-line ART regimens (durability, tolerance)

– Growth abnormalities and response to ART

– Incidence of tuberculosis, opportunistic infections, ART response in relation to prior PMTCT exposure cannot be investigated with the currently available data

• Repeat site assessment within IeDEA framework and/or specific survey on the practice of virological testing and viral resistance

• Initiate the development of a medico-economic model of pediatric care in Africa (“à la Freedberg”) using the KIDS-ART-LINC data set and network

• No new merger outside of very specific objectives

International epidemiological Databases to Evaluate AIDS

• 7 regional networks• North America• South America / Caribbean• West Africa• Central Africa• East Africa• Southern Africa• Australia / Asia

• Resource limited countries networks• KIDS-ART-LINC Collaboration• Treat Asia HIV Observational Database (TAHOD)

www.iedea-hiv.orgwww.anecca.orgwww.amfar.org

International epidemiological Database to Evaluate AIDS (IeDEA)

West AfricaPediatric Working group

Valériane Leroy, Alain Azondékon

Study population(N = 2204 children on HAART)

Country Center Number of Children under

HAART%

Bénin UPEIV 71 3

Côte d’Ivoire CePReF 309 14

Côte d’Ivoire CHU Yopougon 669 31

Côte d’Ivoire CIRBA 141 6

Côte d’Ivoire MTCT-Plus 74 3

Gambie FAJARA 23 1

Ghana Korle BU Hosp 128 6

Mali Hop G. Touré 674 31

Sénégal Hop A Royer 115 5

Total 2204 100

Bases de données observationnelles

Conclusions (février 2008) • L’ANRS seule ne peut pas maintenir des bases de

données internationales dans les pays à resources limitées : quid de la politique de sites ?

• Le partenariat avec les NIH est possible, mais : – La collaboration IeDEA est le nouveau cadre de référence – On ne pourra constituer de nouveaux “mergers” de

données inter-régionales (adultes ou pédiatriques) qu’en rapport avec des objectifs très spécifiques

• Réorienter les demandes de soutien à l’ANRS en fonction de ce nouveau contexte