1. Bases de données observationnelles AC12 Bilan 2007 et Objectifs 2008

2. 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 ART Cohort Collaboration

3. The Antiretroviral Therapy in Low-Income Countries (ART-LINC) Collaboration ANRS 12101 / 12138 & NIH/OAR Dabis, Egger, Schechter A network of 21 HIV treatment programs and 47 clinical centers in Africa (Morocco, Senegal, Côte dIvoire, 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

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

6. Mortality over four years Sub-Saharan Africa Europe & North America CROI 2007 – Egger Plenary

8. Sustained long term CD4 response to ART among naïve patients in low income countries Denis Nash - CROI 2008

9. Sustained long term CD4 response to ART among naïve patients in low income countries D. Nash - CROI 2008 Most important determinant of CD4 trajectory after ART initiation is baseline CD4 (increasing with calendar time at most sites)

10. 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 Tuberculosis in the first year after Initiation of ART in Low-Income and High-Income Countries The ART-LINC Collaboration and The ART Cohort Collaboration CID 2007:45 (1 December)

11. Probability of death or lost-to-follow-up in 2,710 adults starting ART at WHO stage 1 or 2 and CD4 >200/mm 3 or unknown, according to CTX prescription (C. Lewden in progress) P=0.006 Adjusted HR: 046 (0.30-0.73)

12. Coût-efficacité de stratégies de rétention des patients sous ART Hapsatou Touré, Xavier Anglaret, Elena Losina François Dabis, Ken Freedberg Objectif général Comparer lefficacité 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, …)

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

14. 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.org www.art-linc.org www.amfar.org

15. International epidemiological Database to Evaluate AIDS (IeDEA) IeDEA – West Africa Coordinating Investigators François DABIS (France) Emmanuel BISSAGNENE (Côte dIvoire) Project Manager Didier K. EKOUEVI Progress report - February 2008

16. Adult clinical centers in West Africa (N = 16,945) NameLocationNumber of patients on HAART USACCôte dIvoire2442 CePReFCôte dIvoire3393 MTCT-PlusCôte dIvoire461 SMITCôte dIvoire4608 CIRBACôte dIvoire2272 CNTSCôte dIvoire716 Toure HospitalMali1113 Point GMali431 CNHUBenin872 ANRS 1215Senegal404 MRCGambia233

17. 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%

18. 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]

19. 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

20. 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 dIvoire)

21. Paediatric ART in Sub-Saharan Africa: the multi-center KIDS-ART-LINC collaboration Dabis, Mbori-Ngacha ANRS 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 http://www.rcqhc.org/kids-art-linc

23. 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 oCROI 2007 (Los Angeles) – February 2007 oPEPFAR 2007 (Kigali) – June 2007 oManuscript submitted

24. Delay in start ART until immunodeficiency results in excess mortality, most in 1 st six months treatment Arrive CROI 2007 (cité par Mofenson - CROI 2008) Months from ART startProbability of death after starting ART Immune Deficient at Start ART Not Immune Deficient at Start ART 6 months 7.8%1.8% 12 months 8.2%2.2% Meta-analysis 1,195 children from 8 African data bases 53% >5 years of age, 66% severe age-related immune deficiency ARV: NNRTI-based 58%, PI-based 37% 6% excess mortality 0.4% after 6 mos 0.4% after 6 mos

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

26. 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

27. 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.org www.anecca.org www.amfar.org

28. International epidemiological Database to Evaluate AIDS (IeDEA) West Africa Pediatric Working group Valériane Leroy, Alain Azondékon

29. Study population (N = 2204 children on HAART) CountryCenterNumber of Children under HAART % BéninUPEIV71 3 Côte dIvoireCePReF30914 Côte dIvoireCHU Yopougon66931 Côte dIvoireCIRBA141 6 Côte dIvoireMTCT-Plus74 3 GambieFAJARA23 1 GhanaKorle BU Hosp128 6 MaliHop G. Touré67431 SénégalHop A Royer115 5 Total2204100

30. Bases de données observationnelles Conclusions (février 2008) LANRS 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) quen rapport avec des objectifs très spécifiques Réorienter les demandes de soutien à lANRS en fonction de ce nouveau contexte