1. Trends in mortality among HIV-infected subjects;
TUPDC0105
Trends in mortality among HIV-infected subjects;
differences by HCV coinfection
Belen Alejos for the Trends in cause-specific mortality working group of COHERE in EuroCoord
Conflicting of interest disclosure: None
Objective
To study trends from in overall and cause-specific mortality, stratified by HCV status, among HIV-positive adults within the Collaboration of Observational HIV Epidemiological Research Europe (COHERE).
Methods
Outcome
Cause-specific mortality groups were based on a simplified algorithm adapted from the CoDe coding system
COHERE – Collaboration of Observational HIV Epidemiological Research in Europe in EuroCoord
HIV+, Western European countries, >16 years and after 1st January 2000
Antiretroviral naïve at baseline
One HCV antibody test result
Cohorts with causes of deaths or HCV-status missing in <50% of patients
Coinfection by Hepatitis C Virus (HCV) is one of the most common comorbidities in HIV-infected patients.
The objective of this study is To study trends in overall mortality and cause-specific mortality stratified by HCV in people living with HIV in Europe in the period
METHODS
Baseline was defined as the date of cohort recruitment for patients with known HCV status at recruitment, or if unknown the date of first HCV test after recruitment. Individuals were followed up from baseline to death or last study contact whichever arose first
Based on this information about Cause of Death and additional data available in COHERE we created cause-specific groups using the simplified algorithm based on the CoDe coding system (Revised CoDe) for those cohorts that have less than 50% of unknown causes of deaths
Statistical analyses
Two calendar periods : &
Multivariable Poisson regression:
Overall and cause-specific adjusted mortality Rate Ratios (aRR) for the effect of calendar period (ref )
Stratified by HCV coinfection
Multiple Imputation by Chained Equations
Baseline
Known HCV status at entry  date of cohort recruitment
Unknown HCV status at entry date of first HCV test after recruitment

2. Results Trends in mortality among HIV-infected subjects;
differences by HCV coinfection
Results
Subjects characteristics
Cause of death distribution
Subjects characteristics
Between , 64,209 patients were included. The median age at baseline was 36 years old. 72% were males. 13% were HCV-positive at baseline. Among HCV positive patients, the main risk for HIV transmission was IDU (61.3%) while among HCV negative patients, the most frequent group was heterosexual (53.5%)
Cause of death distribution
In the down part of the slide we present the distribution of causes of detah stratified by HCV coinfection and calendar period. During follow-up, 2,774 deaths were identified. In both periods—and in both HCV positive patients and HCV negative patients—HIV/Aids was the leading cause of mortality, followed by NADM among monoinfected patients, and by liver disease among coinfected patients.
Although it has remained the most common cause over the whole follow-up period, the percentage of all deaths attributable to HIV/Aids decreased from 42.1% in to 33.9% in Nevertheless, the proportion NADM related deaths increased over time (11.3% to 18.5%).
(Non-AIDS-malignancies)

3. Mortality Rates per 1000 py and adjusted effect of calendar period (ref. 2000-2007)
Overall
Non-AIDS Infections
HIV/AIDS
NADM
NADM
Liver
aRR (95% CI)
0.77 ( )
0.73 ( )
0.57 ( )
0.71 ( )
1.15 ( )
1.07 ( )
0.47 ( )
0.86 ( )
0.60 ( )
0.55 ( )
Cardiovascular
Psychiatric
External
Pulmonary
In the slide we present overall and cause-specific death rates stratified by HCV-status and calendar period. In small blue boxes you can see Adjusted mortality Rate Ratios for the effect of calendar period taking the first period as reference for HCV- and for HCV+ subjets.
The overall MR for all-cause mortality was 8.2 per 1000 py. MRs were substantially higher in HCV-coinfected patients for all causes of death and in both periods except from external mortality and cardiovascular mortality in the second period.
Overall, HIV/AIDS and Non AIDS defining Infections mortality declined from to for both mono and co-infected individuals. . Liver related decreased in both populations although the relative decrease was larger among HCV-negatives
Cardiovascular mortality increased almost two-fold among HCV-positives whereas it remained practically constant among HCV-negatives
aRR (95% CI)
1.12 ( )
1.99 ( )
1.41 ( )
0.71 ( )
1.43 ( )
1.17 ( )
1.08 ( )
0.86 ( )
Conclusions
HCV-coinfection is associated with increased overall and cause-specific mortality among HIV-positive patients.
Significant relative reductions in overall mortality –as well as in AIDS, Liver and Non-AIDS infections over time were observed for both mono and coinfected patients.

4. Project leaders and statistical analysis:
Acknowledgements
Project leaders and statistical analysis:
Juan Berenguer, Julia Bohlius, Vincent Bouteloup, Heiner Bucher, Alessandro Cozzi-Lepri, François Dabis, Antonella d’Arminio Monforte, Mary-Anne Davies, Julia del Amo, Maria Dorrucci, David Dunn, Matthias Egger, Hansjakob Furrer, Marguerite Guiguet, Sophie Grabar, Ali Judd, Ole Kirk, Olivier Lambotte, Valériane Leroy, Sara Lodi, Sophie Matheron, Laurence Meyer, Jose Mª Miró, Amanda Mocroft, Susana Monge, Fumiyo Nakagawa, Roger Paredes, Andrew Phillips, Massimo Puoti, Eliane Rohner, Michael Schomaker, Colette Smit, Jonathan Sterne, Rodolphe Thiebaut, Claire Thorne, Carlo Torti, , Marc van der Valk, Linda Wittkop.
Project Working Group
Juan Berenguer, Julia del Amo, Belén Alejos Niels Obel, Cristina Mussini, Ferdinand Wit, Stéphane de Wit, Veronica Svedhem Johansson,Jannie van der Helm, Carlo Torti , Kholoud Porter , Antonella Castagna, Robert Zangerle, Giota Toulumi, Fabrice Bonnet, Dominique Salmon, Antonella d’Arminio, Anna Esteve, Bernadino Roca, Jonathan Sterne, Maria Athena Campbell, Geneviève Chêne
Steering committee:
Executive Committee: Stéphane de Wit (Chair, St. Pierre University Hospital), Jose Mª Miró (PISCIS), Dominique Costagliola (FHDH), Antonella d’Arminio-Monforte (ICONA), Antonella Castagna (San Raffaele), Julia del Amo (CoRIS), Amanda Mocroft (EuroSida), Dorthe Raben (Head, Copenhagen Regional Coordinating Centre), Geneviève Chêne (Head, Bordeaux Regional Coordinating Centre). ).
Steering Committee - Contributing Cohorts: Ali Judd (AALPHI) Robert Zangerle (AHIVCOS),Giota Touloumi (AMACS), Josiane Warszawski (ANRS CO1 EPF/ANRS CO11 OBSERVATOIRE EPF), Laurence Meyer (ANRS CO2 SEROCO), François Dabis (ANRS CO3 AQUITAINE), Murielle Mary Krause (ANRS CO4 FHDH), Jade Ghosn (ANRS CO6 PRIMO), Catherine Leport (ANRS CO8 COPILOTE), Linda Wittkop (ANRS CO13 HEPAVIH), Peter Reiss (ATHENA), Ferdinand Wit (ATHENA), Maria Prins (CASCADE), Heiner Bucher (CASCADE), Diana Gibb (CHIPS), Gerd Fätkenheuer (Cologne-Bonn), Julia Del Amo (CoRIS), Niels Obel (Danish HIV Cohort), Claire Thorne (ECS), Amanda Mocroft (EuroSIDA), Ole Kirk (EuroSIDA), Christoph Stephan (Frankfurt), Santiago Pérez-Hoyos (GEMES-Haemo), Osamah Hamouda (German ClinSurv), Barbara Bartmeyer (German ClinSurv), Nikoloz Chkhartishvili (Georgian National HIV/AIDS), Antoni Noguera-Julian (CORISPE-cat), Andrea Antinori (ICC), Antonella d’Arminio Monforte (ICONA), Norbert Brockmeyer (KOMPNET), Luis Prieto (Madrid PMTCT Cohort), Pablo Rojo Conejo (CORISPES-Madrid), Antoni Soriano-Arandes (NENEXP), Manuel Battegay (SHCS), Roger Kouyos (SHCS), Cristina Mussini (Modena Cohort), Pat Tookey (NSHPC), Jordi Casabona (PISCIS), Jose M. Miró (PISCIS), Antonella Castagna (San Raffaele), Deborah_Konopnick (St. Pierre Cohort), Tessa Goetghebuer (St Pierre Paediatric Cohort), Anders Sönnerborg (Swedish InfCare), Carlo Torti (The Italian Master Cohort), Caroline Sabin (UK CHIC), Ramon Teira (VACH), Myriam Garrido (VACH). David Haerry (European AIDS Treatment Group)
Paediatric cohort representatives: Ali Judd, Pablo Rojo Conejo
European AIDS Treatment Group: David Haerry.
Finally, I would like to thank to all the COHERE for the opportunity of conducting this project and specially to the working group for their support. And specially I want to thank jonathan Sterne, Margaret May and Adam Tricky their help with the cause of deaths codification.
Regional Coordinating Centres: Bordeaux RCC: Diana Barger, Christine Schwimmer, Monique Termote, Linda Wittkop; Copenhagen RCC: Maria Campbell, Casper M. Frederiksen, Nina Friis-Møller, Jesper Kjaer, Dorthe Raben, Rikke Salbøl Brandt
Sources of funding: The COHERE study group has received unrestricted funding from: Agence Nationale de Recherches sur le SIDA et les Hépatites Virales (ANRS), France; HIV Monitoring Foundation, the Netherlands; and the Augustinus Foundation, Denmark. The research leading to these results has received funding from the European Union Seventh Framework Programme (FP7/ ) under EuroCoord grant agreement n° A list of the funders of the participating cohorts can be found on the Regional Coordinating Centre websites at and