Trends and determinants of severe morbidity in HIV-infected patients: emerging role of bacterial infections, cardiovascular and psychiatric diseases: ANRS CO3 Aquitaine Cohort, 2000-2004.

1
Trends and determinants of severe morbidity in
HIV-infected patients emerging role of
bacterial infections, cardiovascular and
psychiatric diseases ANRS CO3 Aquitaine Cohort,
2000-2004.
F Bonnet1,2, G Chêne2, R Thiébaut2,3, M Dupon1, S
Lawson-Ayayi2, JL Pellegrin1, F Dabis2, P
Morlat1,2 for the Groupe dEpidémiologie
Clinique du SIDA en Aquitaine (GECSA)4 1 CHU de
Bordeaux, Services de Médecine Interne et
Maladies Infectieuses, F-33075 Bordeaux, France
2INSERM, U593, Université Victor Segalen, ISPED,
Bordeaux, F-33076 Bordeaux, France  3INSERM,
EMI03-38, Université Victor Segalen, ISPED,
F-33076 Bordeaux, France, 4 CHU de Bordeaux,
Centre dInformation et de Soins de
lImmunodéficience Humaine (CISIH), F-33076
Bordeaux, France.

• BACKGROUND
• Previous studies on the causes of mortality of
  HIV-infected patients in the era of CART have
  shown that AIDS events are currently associated
  with less than 50 of the deaths and that other
  causes of death are emerging, like liver and
  cardiovascular diseases, infections and neoplasia
  (1-3).
• The causes of severe morbidity leading to
  hospitalization or death in HIV-infected patients
  are poorly described in the era of cART, partly
  because, in most of the cohorts, only AIDS events
  and sometimes specific events (i.e iatrogenic,
  cardiovascular, or cancer) are systematically
  recorded and documented.

OBJECTIVE To study the repartition and the
evolution of severe morbidities, leading to
hospitalization or death during the period
2000-2004, in the setting of a large cohort of
HIV-infected patients where all severe events are
systematically recorded and coded according to
the International Classification of Diseases 10th
revision (ICD10).

• PATIENTS AND METHODS
• - ANRS CO3 Aquitaine Cohort open cohort,
  initiated at the Bordeaux University Hospital and
  four other public hospitals in the Aquitaine
  region (southwestern France) in 1987.
• All adult in- or out-patients of the
  participating hospital wards who have an HIV-1
  infection confirmed by Western blot testing, at
  least one follow-up visit after enrollment or a
  documented date of death and who provide an
  informed consent are eligible for inclusion. A
  standardized questionnaire containing data from
  different categories epidemiological, clinical
  events since last medical contact whether or not
  HIV-related, laboratory and therapeutic is
  recorded by physicians and research nurses at
  each contact.
• All events are coded according to the
  International Classification of Diseases 10th
  revision (ICD10).
• A severe morbid event was defined as a clinical
  diagnosis associated with hospitalization or
  death according to the ICD10 between 2000 and
  2004. Clinical events not associated with
  hospitalization are not included in the current
  analysis.
• - Yearly incidence rates were calculated
  according to the number of patients actively
  followed on that specific year and for each
  diagnosis. Statistical test for trend among
  calendar period was performed using Poisson
  regression (Proc Gen Mod, SAS system software
  version 8.0, SAS Institute). The association
  between potential determinants and the presence
  of a clinical event every semester from 2000 and
  2004 was analyzed with a marginal logistic
  regression using a GEE (Generalized Estimating
  Equations) approach for taking into account
  repeated measures in each patient.

RESULTS Between 2000 and 2004, 3863 HIV-infected
patients had at least one contact reported in the
ANRS CO3 Aquitaine Cohort. The number of patients
reporting at least one contact per year steadily
increased from 2756 in 2000, to 2976 in 2004.
Overall, 1186 patients were hospitalized at least
once, resulting in 1854 hospitalizations for
severe morbidity. Between 2000 and 2004, the
yearly rate of hospitalizations/1000 patients
decreased by 46 from 173 in 2000 to 92 in 2004.
The yearly rate of hospitalized patients/1000
patients decreased by 41 from 132 in 2000 to 78
in 2004.
Figure 2 Incidence rate of severe morbid events
per year of occurrence leading to hospitalization
or death (ICD10 coding), ANRS CO3 Aquitaine
Cohort, 2000-2004
Figure 1 Proportions of severe morbid events
leading to hospitalization or deaths (ICD10
coding) (n1854), ANRS CO3 Aquitaine Cohort,
2000-2004
Median CD4 count IQR
57 14-180
261 135-455
347 196-521
383 225-575
230 115-423
333 141-538
290 158-466
268 158-423
273 107-487
327 296-620
300 133-526
Test for trend assume linear decrease of
incidence across calendar year Test for trend
excluding 2004 Test for trend including 2004
P001

• COMMENTS
• AIDS events are no longer the first cause of
  severe morbidity, since they are associated with
  only 20 of hospitalization between 2000 and 2004
  
• Bacterial infection, psychiatric events,
  cardiovascular diseases, digestive events (mainly
  cirrhosis), viral infections and non-AIDS cancers
  contributed for nearly 60 of the causes of
  severe morbidity.
• The rate of most of these events decreased
  between 2000 and 2004 except for cardiovascular
  diseases and non-AIDS cancers.
• Although the rate of severe morbidity is higher
  in patients highly immuno-compromised, a large
  proportion of severe events occur in patients
  with CD4 count between 200 and 500. Other
  determinants of severe morbidity include age,
  injection drug use, and duration of
  seropositivity, AIDS stage, HIV-RNA, hemoglobin,
  and absence of antiretroviral therapy.
• HIV-related morbidity spectrum is no longer
  limited to AIDS events 1993 CDC classification
  and has shifted from AIDS-related to non
  AIDS-related causes. Ageing, co-morbidities as
  well as addictive behaviors might explain this
  evolving distribution of severe morbidity.
  Immunodepression, even moderate may also play a
  role in the occurrence of some non-AIDS events.
• Limiting endpoints to AIDS events and death is
  insufficient to describe HIV disease progression
  in the era of cART and collection of simple but
  standardized categories should be discussed in
  observational cohorts and clinical trials.

Table Characteristics of patients at the time of
any events compared to those of patients without
severe morbidity between 2000 and 2004, ANRS CO3
Aquitaine Cohort.
Characteristics At any events (N1854) Without event (N2464) Multivariable comparison
RR p
Gender male () 75 73 1.56 1.26 1.93 lt0.001
Age (years, Median, IQR, for ten years older) 41.5 37.1-48.2 39.9 35.2-45.6 1.21 1.13 1.31 lt0.001
Known duration of HIV positive serology (years, Median, Interquartile range, for ten years more) 10.0 5.9-13.5 9.0 5.0-13.0 1.23 1.05 1.44 lt0.001
Transmission group () Men who have sex with men Heterosexual contact Intravenous drug users Blood recipients Others/Undetermined 35 23 30 5 7 40 32 19 3 6 Ref 0.85 0.68 1.05 1.58 1.26 1.99 1.00 0.68 1.48 1.10 0.82 1.48 lt0.001
AIDS stage before event () 43 14 2.03 1.71 1.41 lt0.001
CD4 (/mm3) (median, IQR, for 100 cells higher) 250 88-452 489 349-671 0.87 0.83 0.91 lt0.001
HIV RNA (copies/mL) (median, IQR, for 1 log higher) 3218 51-74067 138 lt50-3704 1.16 1.09 1.22 lt0.001
Hemoglobin level (g/L) (median, IQR, for 1g/L higher) 125 109-139 142 133-151 0.70 0.66 0.73 lt0.001
Positive HCV antibodies (N1001) () 37 27 1.16 0.87 1.56 0.46
Positive HBs antigen (N1017) () 7 7 0.90 0.60 1.34 0.54
Not treated with cART at the time of the event () 23 14 1.59 1.30 1.94 lt0.001
Abreviations RR Rate Ratio HCV hepatitis C
virus cART combination antiretroviral therapy
Number of patients with available information, a
missing indicator was defined in the
multivariable analysis Also adjusted for the
semester from 2000 to 2004 OR0.91 0.89 0.93
for one semester later
References 1- Sabin CA et al. Deaths in the era
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2-Bonnet et al. Causes of death among
HIV-infected patients in the era of highly active
antiretroviral therapy. HIV Medicine. 2002
3195-99. 3-Lewden et al. Causes of death among
HIV-infected adults living in industrialized
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Composition of the GECSA Organization and
methodology G Chêne, F Dabis, R Thiebaut and R
Salamon Clinical coordination D Lacoste, D
Malvy, I Pellegrin, JF Moreau, M Dupon, P Morlat,
JL Pellegrin, and JM Ragnaud. Participating
hospital departments (participating physicians)
Bordeaux University Hospital P Morlat (M
Bonarek, N Bernard, D Lacoste, F Bonnet), C
Beylot (MS Doutre), C Conri (J Constans), P
Couzigou, H Fleury (B Masquelier, I Pellegrin), M
Dupon (H Dutronc), JL Pellegrin, M Longy-Boursier
(P Mercié, D Malvy), JF Moreau (JL Taupin), JM
Ragnaud (C De La Taille, D Neau) Dax Hospital
M Loste (I Blanchard, L Caunègre, A Pons)
Bayonne hospital F Bonnal (Y Blanchard, S
Farbos, MC Gemain) Libourne Hospital J
Ceccaldi, B Darpeix, and P Legendre Villeneuve
sur lot Hospital E Buy. Data management and
analysis S Lawson-Ayayi, E Balestre, G Palmer, D
Touchard. Data collection MJ Blaizeau, M Decoin,
S Delveaux, AM Formaggio, M Pontgahet, B
Uwamaliya.