1. 1 Severe morbidity among HIV- infected patients : a comparison between a Brazilian and a French clinic based observational 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 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 Systemic events (2) –Digestive –Psychiatric –Haematological –Kidney & Urological –Endocrinal –Dermatological –Gynecological –Neurological –Ophtalmologic –Respiratory –Rheumathologic –Traumatic Others

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