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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

Outline

• Background

• Questions and objectives

• Methods– Definitions– Classification– Events validation and data quality

• Preliminary results

• Timelines

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

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

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.

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)

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

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

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

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

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

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