Discussion
This is the first study that employs a concise set of indicators, based on current treatment guidelines, to assess and compare the delivery of health care in a large and heterogeneous population of HIV patients across countries with highly varying levels of resources. By testing this new set of HCI, the study addresses an intriguing question of quality of HIV care on a regional level rather than the evaluation of clinical status of an individual patient. Further, this set of HCI could be adjusted and used to evaluate the efficacy of treatment programmes for HIV-positive people elsewhere. The evaluation of health systems performance represents an important yet often overlooked instrument for improving the management of HIV infection. The main focus of the current HCIs is clinical management of HIV patients, rather than clinical outcomes, recently published [
15]. The results of this previous study demonstrated an increased mortality in EE, particularly from AIDS related events, which is consistent with our findings herein of poorer HCI, particularly proportion of time virologically suppressed, in EE. More specifically, a data-driven identification of the best level of health care utilisation allows for establishing a clinical benchmark for HIV care which, in turn, enables the detection of gaps and facilitates continuous quality improvement of the management of HIV infection.
The assessment of health care quality in general is an essential component of disease management. A benchmark should represent a clinically realistic level of excellence and at the same time exceed mean performance [
16]. To evaluate the utilisation of HIV care we chose specific clinical process-of-care indicators measuring adherence to existing guidelines (HCIs 1–3), as well as quality outcome measures, i.e. the ability to achieve the best clinical response after the initiation of cART (HCI 4). We aimed to identify a set of simply measurable HCI, which could be easily implemented in any setting.
Although current analysis documents substantial differences in the utilisation of HIV care across Europe and Argentina, underlying reasons for these differences should be a subject for further investigation. Whereas there were only few and generally minor differences between NE, WCE, and SE in most HCIs, EE, AR and to some extent ECE differed significantly from the rest of the regions. In terms of time of cART initiation, a significantly higher proportion of patients in ECE, EE and AR started cART at a CD4-cell count <200 cells/mm
3 or after an AIDS diagnosis, even in recent years despite changes to guidelines [
1‐
3]. Nevertheless, it is reassuring to see a slight increase over time in the proportion of patients starting cART at higher CD4-cell counts in EE. This is consistent with the fact that access to cART has substantially increased in this region after 2006 [
5]. Late cART initiation could also to some extent be explained by late presentation. In our study most patients in EE starting cART at low CD4-cell count are known HIV-infected, but followed without cART, whereas patients in other regions to a larger extent are late presenters (data not shown). This likely reflects the inclusion criteria for the study. Patients are required to have a pre-booked, outpatient appointment and hence late presenters, who are more likely to die or be admitted to hospital, will not be recruited to the study until they are under routine follow-up.
The use of PCP-chemoprophylaxis was fairly stable over the years in SE, WCE, NE and ECE. Argentina is remarkable by the highest use of PCP-chemoprophylaxis which, for example, could be explained by lower access to cART in the country in the earlier years (<2004), the low cost of co-trimoxazole and a high proportion of late presenters [
17]. EE is considered to have a suboptimal access to cART and a high proportion of AIDS patients [
5]; however, the level of PCP-chemoprophylaxis was rather low in this region, despite the fact that this is a very cheap and accessible method to prevent the disease.
Substantial differences in the frequency of laboratory monitoring for HIV-disease status were observed across the regions. Current guidelines recommend clinical and laboratory evaluation of HIV-disease status at least every half year before initiation of cART and on a 6–12 month basis in clinically stable patients on cART with suppressed HIV-RNA [
1,
3]. Adequate monitoring of untreated patients is important in terms of the timely initiation of cART and the prevention of AIDS and, ultimately, death.
When compared to NE, patients treated with cART in all other regions, except WCE, had significantly lower odds of having suppressed plasma HIV-RNA levels for sustained periods of time. This was particularly true for EE and AR. The observed regional differences were over and above what could be explained by differences in patient characteristics and other factors we could adjust for. There might be some factors, such as socio-economic and infrastructure aspects, which play a role and for which we yet do not have data [
18]. The majority of patients from EE acquired HIV by IDU. This population group is usually younger, more mobile, less integrated into society and less likely to address health care [
19,
20]. The domination in mode of HIV transmission of the IDU population and the likely higher level of active IDU among HIV-positive patients in EE might partially explain the inferior outcome in this region [
18,
20]. However, sensitivity analysis excluding patients with IDU as a HIV risk factor showed consistent results (data not shown).
The main goal of cART is to restore the immune system through the maximal suppression of viral replication and thereby minimise the risk of AIDS developing and death [
3]. Regional comparisons of clinical outcomes have recently been published [
15]. Instead, the cut-off of 90% of time on cART spent with suppressed HIV-RNA was chosen as a benchmark criteria based on a recent analysis of significantly higher rates of virological failure in patients spending less than 90% of time on cART with suppressed HIV-RNA [
14]. While EuroSIDA does not have good data on adherence, likely an important component of any HCI, spending >90% of the time of cART virologically suppressed is probably a marker of good adherence, as those most adherent to cART are most likely to continually suppress viremia [
14].
Limitations of the current analysis should be noted. Further research is needed to investigate the underlying reasons for the identified gaps in HIV care. Late cART initiation, not using PCP prophylaxis in patients with CD4-cell count <200 cells/mm3 or not measuring CD4-cell count and HIV-RNA can be equally related to the specifics of health care infrastructure as well as to the patients’ behaviour. Addressing the issues above will help to plan targeted interventions and quality improvement programmes: whether it should be health care system-, provider- or patient- oriented. Information on countries’ laws regarding HIV-testing might help to better understand the impact of opt-out HIV-testing on late presentation of HIV-infection. EuroSIDA is currently collecting new data and investigating the underlying reasons for differences in HCIs. A health care questionnaire to address site-specific issues within health care utilisation is currently under development. The main HCI we focused on was the virologic response to cART, and HIV-RNA was measured less frequently in EE compared to the other regions of Europe. Therefore, we may have overestimated the proportion of time virologically suppressed in EE, however this fact was taken into account by censoring the follow-up if there were no HIV-RNA measurement for >6 months. Finally, EuroSIDA includes predominantly major HIV clinics, and the cohort might not be representative for the entire HIV-positive population in Europe, and especially so in EE. Hence the real life situation in terms of HIV health care in EE is likely even worse than presented here.
Comparative analysis of health care utilization and identification of benchmarks and gaps should help to better address the problem of managing HIV infection showing a path towards improvement. Lower-income regions would not necessarily soon reach the same level of health care as in high-income regions, but it is important to continually seek improvement. With the current paper we aim to focus public health attention on the HIV care situation in Eastern Europe, prompting further investigations and interventions as appropriate
Acknowledgements
The EuroSIDA Study Group
The multi-centre study group of EuroSIDA (national coordinators in parenthesis).
Argentina: (M Losso), C Elias, Hospital JM Ramos Mejia, Buenos Aires. Austria: (N Vetter), Pulmologisches Zentrum der Stadt Wien, Vienna; R Zangerle, Medical University Innsbruck, Innsbruck. Belarus: (I Karpov), A Vassilenko, Belarus State Medical University, Minsk, VM Mitsura, Gomel State Medical University, Gomel; O Suetnov, Regional AIDS Centre, Svetlogorsk. Belgium: (N Clumeck), S De Wit, M Delforge, Saint-Pierre Hospital, Brussels; R Colebunders, Institute of Tropical Medicine, Antwerp; L Vandekerckhove, University Ziekenhuis Gent, Gent. Bosnia-Herzegovina: (V Hadziosmanovic), Klinicki Centar Univerziteta Sarajevo, Sarajevo. Bulgaria: (K Kostov), Infectious Diseases Hospital, Sofia. Croatia: (J Begovac), University Hospital of Infectious Diseases, Zagreb. Czech Republic: (L Machala), D Jilich, Faculty Hospital Bulovka, Prague; D Sedlacek, Charles University Hospital, Plzen. Denmark: (J Nielsen), G Kronborg,T Benfield, M Larsen, Hvidovre Hospital, Copenhagen; J Gerstoft, T Katzenstein, A-B E Hansen, P Skinhøj, Rigshospitalet, Copenhagen; C Pedersen, Odense University Hospital, Odense; L Ostergaard, Skejby Hospital, Aarhus. Estonia: (K Zilmer), West-Tallinn Central Hospital, Tallinn; Jelena Smidt, Nakkusosakond Siseklinik, Kohtla-Järve. Finland: (M Ristola), Helsinki University Central Hospital, Helsinki. France: (C Katlama), Hôpital de la Pitié-Salpétière, Paris; J-P Viard, Hôpital Necker-Enfants Malades, Paris; P-M Girard, Hospital Saint-Antoine, Paris; JM Livrozet, Hôpital Edouard Herriot, Lyon; P Vanhems, University Claude Bernard, Lyon; C Pradier, Hôpital de l'Archet, Nice; F Dabis, D Neau, Unité INSERM, Bordeaux. Germany: (J Rockstroh), Universitäts Klinik Bonn; R Schmidt, Medizinische Hochschule Hannover; J van Lunzen, O Degen, University Medical Center Hamburg-Eppendorf, Infectious Diseases Unit, Hamburg; HJ Stellbrink, IPM Study Center, Hamburg; S Staszewski, JW Goethe University Hospital, Frankfurt; J Bogner, Medizinische Poliklinik, Munich; G. Fätkenheuer, Universität Köln, Cologne. Greece: (J Kosmidis), P Gargalianos, G Xylomenos, J Perdios, Athens General Hospital; G Panos, A Filandras, E Karabatsaki, 1st IKA Hospital; H Sambatakou, Ippokration Genereal Hospital, Athens. Hungary: (D Banhegyi), Szent Lásló Hospital, Budapest. Ireland: (F Mulcahy), St. James's Hospital, Dublin. Israel: (I Yust), D Turner, M Burke, Ichilov Hospital, Tel Aviv; S Pollack, G Hassoun, Rambam Medical Center, Haifa; S Maayan, Hadassah University Hospital, Jerusalem. Italy: (S Vella), Istituto Superiore di Sanità, Rome; R Esposito, I Mazeu, C Mussini, Università Modena, Modena; C Arici, Ospedale Riuniti, Bergamo; R Pristera, Ospedale Generale Regionale, Bolzano; F Mazzotta, A Gabbuti, Ospedale S Maria Annunziata, Firenze; V Vullo, M Lichtner, University di Roma la Sapienza, Rome; A Chirianni, E Montesarchio, M Gargiulo, Presidio Ospedaliero AD Cotugno, Monaldi Hospital, Napoli; G Antonucci, A Testa, P Narciso, C Vlassi, M Zaccarelli, Istituto Nazionale Malattie Infettive Lazzaro Spallanzani, Rome; A Lazzarin, A Castagna, N Gianotti, Ospedale San Raffaele, Milan; M Galli, A Ridolfo, Osp. L. Sacco, Milan; A d’Arminio Monforte, Istituto Di Clinica Malattie Infettive e Tropicale, Milan. Latvia: (B Rozentale), I Zeltina, Infectology Centre of Latvia, Riga. Lithuania: (S Chaplinskas), Lithuanian AIDS Centre, Vilnius. Luxembourg: (R Hemmer), T Staub, Centre Hospitalier, Luxembourg. Netherlands: (P Reiss), Academisch Medisch Centrum bij de Universiteit van Amsterdam, Amsterdam.Norway: (V Ormaasen), A Maeland, J Bruun, Ullevål Hospital, Oslo. Poland: (B Knysz) J Gasiorowski, Medical University, Wroclaw; A Horban, E Bakowska, Centrum Diagnostyki i Terapii AIDS, Warsaw; A Grzeszczuk, R Flisiak, Medical University, Bialystok; A Boron-Kaczmarska, M Pynka, M Parczewski, Medical Univesity, Szczecin; M Beniowski, E Mularska, Osrodek Diagnostyki i Terapii AIDS, Chorzow; H Trocha, Medical University, Gdansk; E Jablonowska, E Malolepsza, K Wojcik, Wojewodzki Szpital Specjalistyczny, Lodz. Portugal: (F Antunes), M Doroana, L Caldeira, Hospital Santa Maria, Lisbon; K Mansinho, Hospital de Egas Moniz, Lisbon; F Maltez, Hospital Curry Cabral, Lisbon. Romania: (D Duiculescu), Spitalul de Boli Infectioase si Tropicale: Dr. Victor Babes, Bucarest. Russia: (A Rakhmanova), Medical Academy Botkin Hospital, St Petersburg; N Zakharova, St Petersburg AIDS Centre, St Peterburg; S Buzunova, Novgorod Centre for AIDS, Novgorod. Serbia: (D Jevtovic), The Institute for Infectious and Tropical Diseases, Belgrade. Slovakia: (M Mokráš), D Staneková, Dérer Hospital, Bratislava. Slovenia: (J Tomazic), University Clinical Centre Ljubljana, Ljubljana. Spain: (J González-Lahoz), V Soriano, P Labarga, J Medrano, Hospital Carlos III, Madrid; S Moreno, JM Rodriguez, Hospital Ramon y Cajal, Madrid; B Clotet, A Jou, R Paredes, C Tural, J Puig, I Bravo, Hospital Germans Trias i Pujol, Badalona; JM Gatell, JM Miró, Hospital Clinic i Provincial, Barcelona; P Domingo, M Gutierrez, G Mateo, MA Sambeat, Hospital Sant Pau, Barcelona.Sweden: (A Karlsson), Venhaelsan-Sodersjukhuset, Stockholm; L Flamholc, Malmö University Hospital, Malmö. Switzerland: (B Ledergerber), R Weber, University Hospital, Zürich; P Francioli, M Cavassini, Centre Hospitalier Universitaire Vaudois, Lausanne; B Hirschel, E Boffi, Hospital Cantonal Universitaire de Geneve, Geneve; H Furrer, Inselspital Bern, Bern; M Battegay, L Elzi, University Hospital Basel. Ukraine: (E Kravchenko), N Chentsova, Kiev Centre for AIDS, Kiev; V Frolov, G Kutsyna, Luhansk State Medical University; Luhansk; S Servitskiy, Odessa Region AIDS Center, Odessa; M Krasnov, Kharkov State Medical University, Kharkov. United Kingdom: (S Barton), St. Stephen's Clinic, Chelsea and Westminster Hospital, London; AM Johnson, D Mercey, Royal Free and University College London Medical School, London (University College Campus); A Phillips, MA Johnson, A Mocroft, Royal Free and University College Medical School, London (Royal Free Campus); M Murphy, Medical College of Saint Bartholomew's Hospital, London; J Weber, G Scullard, Imperial College School of Medicine at St. Mary's, London; M Fisher, Royal Sussex County Hospital, Brighton; C Leen, Western General Hospital, Edinburgh.
Steering Committee: J Gatell, B Gazzard, A Horban, B Ledergerber, M Losso, J Lundgren, A d’Arminio Monforte, C Pedersen, A Phillips, A Rakhmanova, P Reiss, M Ristola, J Rockstroh (Chair), S De Wit (Vice-Chair).
Coordinating Centre Staff: J Lundgren, O Kirk, A Mocroft, A Cozzi-Lepri, D Grint, M Ellefson, D Podlekareva, J Kjær, L Peters, J Reekie, J Kowalska, J Tverland, A H Fischer, J Nielsen.