FIOCRUZ: Prof B Grinsztejn INSERM: Prof G Chêne Joint call INSERM-FIOCRUZ 2009-2011

1. Severe morbidity among HIV-infected patients : a comparison between a Brazilian and a French clinic basedobservational cohort • FIOCRUZ: Prof B Grinsztejn • INSERM: Prof G Chêne • Joint call INSERM-FIOCRUZ 2009-2011

2. Outline • Background • Questions and objectives • Methods • Definitions • Classification • Events validation and data quality • Preliminary results • Timelines

3. Background • Generalized access to combination Anti-Retroviral Therapy (cART) • dramatically improved outcome • disease progression remains highly variable • shift from AIDS- to non AIDS-related mortality/morbidity • ageing, hepatitis C co-infection, tobacco smoking and other addictions, long-term exposure to antiretrovirals • virus mutations, introduction of new drugs/drug classes • Important to continuously assess changes and their impact on disease progression, though life expectancy still not at the level of general population

4. Questions • Trends of the severe morbid process? • Causes of severe morbidity: AIDS, cardio-vascular, cancer, non AIDS infections, etc. poorly described so far • Intercontinental comparisons to explain variability in the distribution • Access to therapy • Baseline characteristics • HIV-related (CD4, plasma HIV-RNA) • Others (Co-infections, age, gender, transmission group,..) • Environment

5. Objectives • In the setting of two large cohorts of HIV-infected patients: one from southwestern France (ANRS CO3 Aquitaine) and one from Rio de Janeiro Brazil (IPEC/Fiocruz HIV Clinical Cohort) where all severe events are systematically and prospectively recorded and coded according to the International Classification of Diseases 10th revision (ICD10), • we will aim at studying the repartition and the evolution of causes of severe morbid events occurring in HIV-infected patients during the period 2000-2008. In addition, the role of potential determinants including age, gender, immunodeficiency and uncontrolled viral load, main classes of antiretrovirals and co-infections will also be estimated.

6. Methods: definitions • Inclusion criteria: all patients with ≤1 follow-up (January 2000 – December 2008) • Outcome: Occurrence of a severe morbid event • Severe morbidity: morbid condition leading to at least 48 hrs of hospitalization, or death (as many events as causes of hospitalization for a given hospital stay) • May not be considered as severe morbid events: • Hospitalizations <48 hrs • Hospitalizations due to check-up, planned chemotherapies,…whatever their duration • Coding of the morbid events: • ICD 10 classification (IPEC Cohort) • Simplified version of the ICD 10 (Aquitaine Cohort)

7. Classification: methods • Exclusive classification with decreasing priority: • AIDS events • Non AIDS cancer • Infectious events • Systemic events • IPEC Cohort: • All discharge charts of hospitalization were reviewed to identify morbid events • Each event was coded (ICD10) and classified • Aquitaine Cohort: • Each code of the thesaurus (simplified version of the ICD10) corresponding to events codes was attributed to one category • Codes colligated in the database corresponding to morbid events were extracted and classified in the corresponding category

8. Classification: categories • Systemic events (2) • Digestive • Psychiatric • Haematological • Kidney & Urological • Endocrinal • Dermatological • Gynecological • Neurological • Ophtalmologic • Respiratory • Rheumathologic • Traumatic • Others • AIDS events • Non AIDS cancers • Invasive tumors • In situ tumors • Infectious events • Bacterials • Virals • Parasitic • Systemic events (1) • Cardio-Vascular • Hepatic • Viral-related • Non viral related

9. Validation process • Comparison of the list of codes used by the two cohorts in each category: all discrepancies were discussed • In main instances an agreement was found • For some specific codes it was decided to consider them in different categories in both cohorts: ie K52.9 • IPEC: Chronic diarrhea: Digestive • Aquitaine: Gastro-enteritis rectosigmoïditis: Bacterial • Validation of the events (through medical files): • A specific form was established, to be used by both cohorts • IPEC: 10% of the events validated • Aquitaine: 1% of the events validated

10. Other variables • A specific SOP was established to merge the data of both Cohorts • Variables: • Demographics (Age, gender, educational level,..) • HIV Related (Risk group, Plasma HIV RNA, CD4, treatments,..) • Risk Factors (Tobacco, alcohol, eepatitis co-infections,..) • Checks will be performed after the merger to assess data quality

11. Preliminary results • Aquitaine Cohort • 5553 eligible events in the database (2000-2008) • 845 AIDS events • 4708 Non-AIDS events: Bacterial infections (20%); Neurologicals (9%); Hepatitis (9%); Hematological (8%); Psychiatric (8%); Digestive (7%);..;Non-AIDS cancer (2.4%). • IPEC-Fiocruz Cohort • 2782 eligible events in the database (2000-2008) • 1095 AIDS events (40%) 1687 Non-AIDS events (60%): Bacterial infections (46%); Hepatitis (2,3%); Psychiatric (5,4%); Non-AIDS cancer (0,6%). • 118 codes discrepancies between the cohorts discussed • Codes used only in one cohort • Codes used in both cohort but initially classified in different categories

12. Timelines • Achieved: • Final decisions concerning • The definition of a severe morbid event • The classification of events to consider (list of categories) • Validation of the events • Ongoing: • Generation of the tables for the data merger and data check • Next stages: • Spring 2011: final data merger and check • Summer 2011: analyses • Autumn 2011: final discussion and draft of a first abstract (CROI 2012) and manuscript