Regional differences in AIDS and non-AIDS related mortality in HIV-positive individuals across Europe and Argentina: the EuroSIDA study

Joanne Reekie, Justyna D Kowalska, Igor Karpov, Jurgen Rockstroh, Anders Karlsson, Aza Rakhmanova, Andrzej Horban, Ole Kirk, Jens D Lundgren, Amanda Mocroft, EuroSIDA in EuroCoord, M Losso, C Elias, N Vetter, R Zangerle, I Karpov, A Vassilenko, V M Mitsura, O Suetnov, N Clumeck, S De Wit, M Delforge, R Colebunders, L Vandekerckhove, V Hadziosmanovic, K Kostov, J Begovac, L Machala, D Jilich, D Sedlacek, J Nielsen, G Kronborg, T Benfield, M Larsen, J Gerstoft, T Katzenstein, A-B E Hansen, P Skinhøj, C Pedersen, L Ostergaard, K Zilmer, Jelena Smidt, M Ristola, C Katlama, J-P Viard, P-M Girard, J M Livrozet, P Vanhems, C Pradier, F Dabis, D Neau, J Rockstroh, R Schmidt, J van Lunzen, O Degen, H J Stellbrink, S Staszewski, J Bogner, G Fätkenheuer, J Kosmidis, P Gargalianos, G Xylomenos, J Perdios, G Panos, A Filandras, E Karabatsaki, H Sambatakou, D Banhegyi, F Mulcahy, I Yust, D Turner, M Burke, S Pollack, G Hassoun, S Maayan, S Vella, R Esposito, I Mazeu, C Mussini, C Arici, R Pristera, F Mazzotta, A Gabbuti, V Vullo, M Lichtner, A Chirianni, E Montesarchio, M Gargiulo, G Antonucci, A Testa, P Narciso, C Vlassi, M Zaccarelli, A Lazzarin, A Castagna, N Gianotti, M Galli, A Ridolfo, A Monforte d'Arminio, B Rozentale, I Zeltina, S Chaplinskas, R Hemmer, T Staub, P Reiss, V Ormaasen, A Maeland, J Bruun, B Knysz, J Gasiorowski, A Horban, E Bakowska, A Grzeszczuk, R Flisiak, A Boron-Kaczmarska, M Pynka, M Parczewski, M Beniowski, E Mularska, H Trocha, E Jablonowska, E Malolepsza, K Wojcik, F Antunes, M Doroana, L Caldeira, K Mansinho, F Maltez, D Duiculescu, A Rakhmanova, N Zakharova, S Buzunova, D Jevtovic, M Mokráš, D Staneková, J Tomazic, J González-Lahoz, V Soriano, P Labarga, J Medrano, S Moreno, J M Rodriguez, B Clotet, A Jou, R Paredes, C Tural, J Puig, I Bravo, J M Gatell, J M Miró, P Domingo, M Gutierrez, G Mateo, M A Sambeat, A Karlsson, L Flamholc, B Ledergerber, R Weber, P Francioli, M Cavassini, B Hirschel, E Boffi, H Furrer, M Battegay, L Elzi, E Kravchenko, N Chentsova, V Frolov, G Kutsyna, S Servitskiy, M Krasnov, S Barton, A M Johnson, D Mercey, A Phillips, M A Johnson, A Mocroft, M Murphy, J Weber, G Scullard, M Fisher, C Leen, J Gatell, B Gazzard, A Horban, J Lundgren, I Karpov, B Ledergerber, M Losso, A D'Arminio Monforte, C Pedersen, A Phillips, A Rakhmanova, M Ristola, P Reiss, J Rockstroh, S De Wit, O Kirk, A Mocroft, A Cozzi-Lepri, D Grint, M Ellefson, D Podlekareva, J Kjær, L Peters, J Reekie, J Kowalska, J Nielsen, J Tverland, A H Fischer, O Kirk, A Mocroft, J Grarup, S deWitt, P Reiss, A Cozzi-Lepri, R Thiebaut, J Rockstroh, D Burger, R Paredes, J Kjær, Joanne Reekie, Justyna D Kowalska, Igor Karpov, Jurgen Rockstroh, Anders Karlsson, Aza Rakhmanova, Andrzej Horban, Ole Kirk, Jens D Lundgren, Amanda Mocroft, EuroSIDA in EuroCoord, M Losso, C Elias, N Vetter, R Zangerle, I Karpov, A Vassilenko, V M Mitsura, O Suetnov, N Clumeck, S De Wit, M Delforge, R Colebunders, L Vandekerckhove, V Hadziosmanovic, K Kostov, J Begovac, L Machala, D Jilich, D Sedlacek, J Nielsen, G Kronborg, T Benfield, M Larsen, J Gerstoft, T Katzenstein, A-B E Hansen, P Skinhøj, C Pedersen, L Ostergaard, K Zilmer, Jelena Smidt, M Ristola, C Katlama, J-P Viard, P-M Girard, J M Livrozet, P Vanhems, C Pradier, F Dabis, D Neau, J Rockstroh, R Schmidt, J van Lunzen, O Degen, H J Stellbrink, S Staszewski, J Bogner, G Fätkenheuer, J Kosmidis, P Gargalianos, G Xylomenos, J Perdios, G Panos, A Filandras, E Karabatsaki, H Sambatakou, D Banhegyi, F Mulcahy, I Yust, D Turner, M Burke, S Pollack, G Hassoun, S Maayan, S Vella, R Esposito, I Mazeu, C Mussini, C Arici, R Pristera, F Mazzotta, A Gabbuti, V Vullo, M Lichtner, A Chirianni, E Montesarchio, M Gargiulo, G Antonucci, A Testa, P Narciso, C Vlassi, M Zaccarelli, A Lazzarin, A Castagna, N Gianotti, M Galli, A Ridolfo, A Monforte d'Arminio, B Rozentale, I Zeltina, S Chaplinskas, R Hemmer, T Staub, P Reiss, V Ormaasen, A Maeland, J Bruun, B Knysz, J Gasiorowski, A Horban, E Bakowska, A Grzeszczuk, R Flisiak, A Boron-Kaczmarska, M Pynka, M Parczewski, M Beniowski, E Mularska, H Trocha, E Jablonowska, E Malolepsza, K Wojcik, F Antunes, M Doroana, L Caldeira, K Mansinho, F Maltez, D Duiculescu, A Rakhmanova, N Zakharova, S Buzunova, D Jevtovic, M Mokráš, D Staneková, J Tomazic, J González-Lahoz, V Soriano, P Labarga, J Medrano, S Moreno, J M Rodriguez, B Clotet, A Jou, R Paredes, C Tural, J Puig, I Bravo, J M Gatell, J M Miró, P Domingo, M Gutierrez, G Mateo, M A Sambeat, A Karlsson, L Flamholc, B Ledergerber, R Weber, P Francioli, M Cavassini, B Hirschel, E Boffi, H Furrer, M Battegay, L Elzi, E Kravchenko, N Chentsova, V Frolov, G Kutsyna, S Servitskiy, M Krasnov, S Barton, A M Johnson, D Mercey, A Phillips, M A Johnson, A Mocroft, M Murphy, J Weber, G Scullard, M Fisher, C Leen, J Gatell, B Gazzard, A Horban, J Lundgren, I Karpov, B Ledergerber, M Losso, A D'Arminio Monforte, C Pedersen, A Phillips, A Rakhmanova, M Ristola, P Reiss, J Rockstroh, S De Wit, O Kirk, A Mocroft, A Cozzi-Lepri, D Grint, M Ellefson, D Podlekareva, J Kjær, L Peters, J Reekie, J Kowalska, J Nielsen, J Tverland, A H Fischer, O Kirk, A Mocroft, J Grarup, S deWitt, P Reiss, A Cozzi-Lepri, R Thiebaut, J Rockstroh, D Burger, R Paredes, J Kjær

Abstract

Background: Differences in access to care and treatment have been reported in Eastern Europe, a region with one of the fastest growing HIV epidemics, compared to the rest of Europe. This analysis aimed to establish whether there are regional differences in the mortality rate of HIV-positive individuals across Europe, and Argentina.

Methods: 13,310 individuals under follow-up were included in the analysis. Poisson regression investigated factors associated with the risk of death.

Findings: During 82,212 person years of follow-up (PYFU) 1,147 individuals died (mortality rate 14.0 per 1,000 PYFU (95% confidence interval [CI] 13.1-14.8). Significant differences between regions were seen in the rate of all-cause, AIDS and non-AIDS related mortality (global p<0.0001 for all three endpoints). Compared to South Europe, after adjusting for baseline demographics, laboratory measurements and treatment, a higher rate of AIDS related mortality was observed in East Europe (IRR 2.90, 95%CI 1.97-4.28, p<.0001), and a higher rate of non-AIDS related mortality in North Europe (IRR 1.51, 95%CI 1.24-1.82, p<.0001). The differences observed in North Europe decreased over calendar-time, in 2009-2011, the higher rate of non-AIDS related mortality was no longer significantly different to South Europe (IRR 1.07, 95%CI 0.66-1.75, p = 0.77). However, in 2009-2011, there remained a higher rate of AIDS-related mortality (IRR 2.41, 95%CI 1.11-5.25, p = 0.02) in East Europe compared to South Europe in adjusted analysis.

Interpretations: There are significant differences in the rate of all-cause mortality among HIV-positive individuals across different regions of Europe and Argentina. Individuals in Eastern Europe had an increased risk of mortality from AIDS related causes and individuals in North Europe had the highest rate of non-AIDS related mortality. These findings are important for understanding and reviewing HIV treatment strategies and policies across the European region.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1. Crude mortality rate across the…
Figure 1. Crude mortality rate across the six different regions.
Cause of death are reported by the site investigator and, since 2004, a Coding of Death in HIV (CoDe) case report form is additionally completed for each fatal case and CoDe methods used to determine the underlying cause of death.
Figure 2. Incidence rate ratio (IRR) for…
Figure 2. Incidence rate ratio (IRR) for all cause, AIDS and non-AIDS related mortality per calendar year of follow-up stratified by region.
(Argentina was excluded from this analysis due to limited power). aadjusted for gender, age*, HIV exposure group, hepatitis B* and C* status, prior AIDS diagnosis, prior non-AIDS diagnosis, hypertension*, diabetes*, anaemia*, smoking status*, CD4 count*, baseline date* and on cART viral load*. badjusted for gender, age*, HIV exposure group, hepatitis B* and C* status, prior AIDS diagnosis, prior non-AIDS diagnosis, hypertension*, diabetes*, anaemia*, CD4 count*, baseline date* and on cART viral load*. *time-updated.

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