Hepatitis C virus (HCV) coinfection has been implicated in a range of extrahepatic diseases in HIV-positive persons including kidney disease [1–6]. Some studies found those with chronic HCV infection had more chronic kidney disease (CKD) compared with those with spontaneously cleared infection [1,3], whereas Butt et al. found no difference comparing those with chronic and cleared infection. Many of the earlier studies were limited by lack of data on HCV-RNA, and were therefore unable to distinguish between chronic untreated or spontaneously cleared HCV infection. The impact of HCV-related systemic inflammation and risk of CKD remains unclear, as highlighted in a recent review .
The introduction of direct-acting antivirals (DAAs) for the treatment of HCV has had a major impact on HCV treatment  with cure rates in excess of 90% in persons coinfected with both HIV and HCV . Case reports have shown that achievement of a sustained virological response (SVR) resulted in improvement in kidney function in persons with HCV-related glomerular nephritis . Cohort studies, including 100–350 persons with SVR and with no known underlying renal disorder, have been unable to document an improvement in kidney function in those with SVR compared with those treated for HCV without SVR [12–14]. One further study reported a protective effect of SVR on CKD , which did not reach statistical significance and did not adjust for baseline renal function. Changes in renal function in these studies was measured in a variety of ways, and while slopes or rate of change in estimated glomerular filtration rate (eGFR) might be useful to study short-term changes in renal function, a more rigorous definition of renal decline requiring confirmed low values over a period of 3 months, such as CKD , has greater clinical relevance, given its association with other clinical events, including cardiovascular disease .
Given the lack of consensus from previous studies, methodological issues, and the limited power and/or follow-up, we sought to investigate the incidence of CKD in a large pan-European multicohort study according to HCV status in HIV-coinfected persons across five groups: anti-HCV-negative, spontaneous HCV-RNA clearers, chronic untreated HCV infection, cured HCV, and HCV-RNA-positive following HCV treatment.
The EuroSIDA study
Persons were included from the EuroSIDA study, a large prospective observational cohort of almost 23 000 HIV-1-positive patients followed in 100 hospitals in 35 European countries with Israel and Argentina. Individuals were enrolled into 10 cohorts from 1994 onward. In cohort 10, all HIV-positive patients were also required to be positive for anti-HCV antibodies (HCV-RNA positive, negative or unknown status). At recruitment, in addition to demographic and clinical data, a complete ART history was obtained together with the most recent CD4+ cell counts and HIV-RNA measurements, as well as all HCV tests, HCV-RNA, HCV genotype, hepatitis B surface antigen (HBsAg), and HBV-DNA. Data is collected prospectively at clinical sites and sent to the coordinating centre at yearly intervals. At each follow-up visit, all CD4+ cell counts, HIV-RNA, HCV tests, HCV-RNA, genotype, and HBsAg results measured since last follow-up are collected, together with start and stop dates for antiretroviral drugs and HCV and HBV drugs. Detailed information about data collected in EuroSIDA can be found at http://www.chip.dk/Ongoing-Studies/EuroSIDA/About.
Methods and definitions
CKD was defined as a confirmed (>3 months apart) eGFR less than 60 ml/min per 1.73 m2 for those with first eGFR greater than 60 ml/min per 1.73 m2 and a confirmed (>3 months apart) 25% decline in eGFR for those with baseline eGFR 60 ml/min per 1.73 m2 or less. eGFRs were calculated using the CKD-EPI formula . All persons with known HCV serostatus and prospective follow-up after 1 January 2004 (start of standardized collection of serum creatinine) were eligible for inclusion. Persons with less than three eGFRs during prospective follow-up were excluded, as were persons with less than 3 months follow-up. Baseline was defined as the first prospective visit in EuroSIDA after 1 February 2004 at which both eGFR and HCV serostatus were measured, and where HCV-RNA was known for those anti-HCV-positive. Persons aged less than 16 at baseline or without a CD4+ cell count and HIV viral load in the 12 months before or 1 month after baseline were excluded.
On the basis of time-updated HCV antibody tests, HCV-RNA and HCV treatment, we defined five HCV groups
- (1) Anti-HCV-negative
- (2) HCV antibody-positive, HCV-RNA-negative, untreated (spontaneous clearers)
- (3) HCV antibody-positive, HCV-RNA-positive, untreated (chronic infections)
- (4) HCV antibody-positive, HCV-RNA-negative, treated (successfully treated with any HCV therapy; cured)
- (5) HCV antibody-positive, HCV-RNA-positive, treated (treated, HCV-RNA positive)
All groups anti-HCV positive were defined on the basis of a single HCV-RNA measurement; for example, persons were classified as spontaneous clearers based on the latest value of HCV-RNA. Those HCV-RNA positive after treatment included persons who did not achieve SVR, persons without an end of treatment response, persons who were HCV-RNA-positive having started treatment more recently and those reinfected with HCV. Persons were followed until their last visit (median June 2018), date of death, or CKD, whichever occurred first. Person-years of follow-up (PYFU) and CKD events accrued according to current HCV strata using the last observation carried forward and persons could contribute PYFU to multiple groups.
In those that developed CKD, we performed an exploratory analysis looking at reversal of CKD. This was defined as a confirmed (> 3 months apart) increase in eGFR to greater than 60 ml/min per 1.73 m2 among persons with at least two further eGFRs and 3 months follow-up after CKD. Baseline for this analysis was date of developing CKD, and individuals were followed to the first of reversal of CKD or last eGFR.
Characteristics of individuals were compared across strata using chi-squared statistics for categorical variables and the Kruskall--Wallis test for continuous variables. Incidence rates of CKD per 1000 PYFU were calculated within HCV groups, and Poisson regression was used to compare these rates with those cured as the reference group. Different models were investigated; the first adjusted only for the Data Collection on Adverse events of Anti-HIV Drugs (D:A:D) study CKD risk score , without including the component because of HCV coinfection. Liver fibrosis stage (as previously described ; this was included as a baseline measurement as it may lie on the causal pathway between HCV status and CKD) and the HCV strata defined above were also included in this model. As the D:A:D CKD risk score does not include all the variables, which differed between the HCV strata, we also investigated a more extensive model adjusting for many more potential confounding variables. This second model adjusted for a greater number of potential confounding factors, all fixed at baseline (sex, HIV exposure group, region of Europe (North, Central West, South, Central East, East and Argentina ), eGFR, HIV viral load, prior AIDS, cardiovascular disease, non-AIDS defining malignancies (NADM), end-stage liver disease (ESLD; ascites, hepatorenal syndrome, grade III/IV hepatic encephalopathy, unspecified liver decompensation, oesophageal variceal bleeding, spontaneous bacterial peritonitis, liver transplantation and hepatocellular carcinoma). Further information about these events is available at https://www.chip.dk/Studies/EuroSIDA/Study-documents). We also adjusted for smoking status (never smoked, current smoker, past smoker, unknown smoking status), hypertension, BMI, use of nephrotoxic antiretrovirals [antiretrovirals: tenofovir, atazanavir (unboosted and/or ritonavir-boosted), indinavir, and lopinavir], use of nephrotoxic drugs (foscarnet, acyclovir, pentamidine, cidofovir, amphotericin B), CD4+ cell count, nadir CD4+, age, liver fibrosis, and baseline date. A third model adjusted for baseline liver fibrosis and the components of the D:A:D CKD risk score (including use of nephrotoxic antiretrovirals and HCV status as defined in this study) at baseline as separate variables rather than a composite score. The model was additionally adjusted for starting integrase inhibitors, shown to increase serum creatinine levels , as a time updated variable. As results were consistent across models, our results focus on model 3, which had the lowest Akaike Information Criterion.
We performed a wide range of sensitivity analyses to investigate the robustness of our results to different assumptions. We performed a sensitivity analysis where the last HCV-RNA measurement was carried forward for a maximum of 12 months. This reduces the bias from HCV-RNA measurements measured many years previously being used to stratify persons into HCV strata. We also excluded persons with stage F3/F4 liver fibrosis at baseline, as well as PYFU and CKD events occurring after the development of F3/F4 liver fibrosis in the subgroup of persons at high risk for CKD using the D:A:D CKD risk score , and an analysis limited to after 2014, when DAAs became more widely available for persons included in the EuroSIDA study . We also explored a more rigorous definition of CKD as a confirmed 25% decline to less than 60 ml/min per 1.73 m2. We repeated our analyses separately among those treated and cured or HCV-RNA-positive after treatment in those not exposed, or only exposed, to DAA-based regimens.
All analyses were performed in SAS version 9.4 (Statistical Analysis Software, Cary, North Carolina, USA).
Of 22 826 persons enrolled in EuroSIDA, 6806 were excluded because of unknown HCV status, insufficient follow-up or with CKD before baseline. An additional 1266 persons were excluded with unknown HCV-RNA status for those who were anti-HCV positive, or with missing baseline CD4+ cell counts and viral load. Compared to the 14 754 included, the 1266 excluded were less likely to be MSM, were less likely to be from Central, or West Europe and more likely to be from Central East, Eastern Europe or Argentina compared with southern Europe. They were also less likely to have suppressed HIV viral load and more likely to have a prior AIDS diagnosis (all P < 0.05).
Table 1 shows the characteristics of the 14 754 included persons, stratified by baseline HCV strata. The five HCV strata were quite heterogenous, and there were many significant differences across the groups (see footnote to Table 1). As would be expected, the proportion of injecting drug uses (IDUs) was lowest in those anti-HCV-negative, the proportion with prior ESLD (only three persons had a prior diagnosis of hepatorenal syndrome) was highest in those HCV-RNA-positive after treatment and the burden from F3/F4 liver fibrosis was the highest in both those cured and HCV-RNA-positive after treatment, as was the proportion who had received tenofovir disoproxil fumarate (TDF) at baseline. The median age was 43 years [interquartile range (IQR) 37--51], baseline CD4+ cell count was 470 cells/μl (IQR 318–669) and CD4+ nadir 174 cells/μl (IQR 70–281). One thousand, seven hundred and sixty-four persons had been previously treated for HCV; the majority of these (1467; 83.2%) had been treated with interferon with ribavirin. At baseline, 181 had received a DAA with interferon, and 275 had received DAAs without interferon.
The analysis included 280 022 eGFRs with a median of 16 (IQR 8–28) per person and 2.4 (IQR 1.9–3.0) per year of follow-up. The number of measures per person per year were similar across the five HCV strata, ranging from 2.2/year (IQR 1.7–3.0) in spontaneous clearers to 2.4 per year in those anti-HCV-negative, those cured and those HCV-RNA-positive after treatment. The median eGFR at baseline was 99 ml/min per 1.73 m2 (IQR 85--110). Four thousand, four hundred and twenty (30%) were at low risk of CKD using the D:A:D risk score, 5089 (34.5%) were at medium risk and 5243 (35.5%) were at high risk, with significant differences between HCV strata. At baseline, 2842 of those anti-HCV-negative were at high risk (30.6%), increasing to 545 of those cured (59.1%) and 425 in those HCV-RNA-positive after treatment (50.5%).
The incidence of chronic kidney disease in hepatitis C virus strata
During 115 335 PYFU; a median 7 (IQR 3.7–12.4) per person, 1130 (7.7%) developed CKD; the crude incidence rate per 1000 person-years of follow-up was 9.8 [95% confidence interval (CI) 9.2–10.4]. Table 2 shows the crude incidence rate in each of the HCV strata. The incidence rate was lowest in those HCV-RNA-positive following treatment; incidence rate 7.7/1000 PYFU (95% CI 5.2–10.1) and highest in those cured; 12.9/1000 PYFU (95% CI 10.4–15.3). Figure 1 shows the multivariate incidence rate ratios of CKD compared with those cured. After adjustment (model 3, adjusting separately for the components of the D:A:D CKD risk score, liver fibrosis stage at baseline and use of integrase inhibitors) those anti-HCV negative [adjusted incidence rate ratio (aIRR) 0.50; 95% CI 0.39–0.63] and spontaneous clearers (aIRR 0.67; 95% CI 0.47–0.97) had significantly lower rates of CKD compared with those cured. Those chronically infected (aIRR 0.85; 95% CI 0.65–1.12) and HCV-RNA-positive after treatment (aIRR 0.71; 95% CI 0.49–1.04) had nonsignificant reduced rates of CKD compared with those cured.
The proportion of follow-up time with eGFR greater than 90 ml/min per 1.73 m2 was 62.5%, and was highest in those with chronic infections (69.2%) and lowest in those cured (55%). Of 1128 who developed CKD, 926 (82.1%) had at least two further eGFRs and 3 months follow-up. Of these 926, 442 (47.7%) had a reversal of CKD during subsequent follow-up. By 12 months after CKD, 17.2% were estimated to have reversed CKD (95% CI 14.7–19.7) from Kaplan--Meier estimates, with no differences between the HCV strata at development of CKD (P = 0.56). The proportion who reversed CKD was lowest overall for those cured (23/72, 31.9%) and highest for those chronically infected (53/102, 52.0%), but this was not statistically significant (P = 0.083). The median eGFR at CKD was 53.4 (IQR 47.2–57.0 ml/min per 1.73 m2) and was lowest in those chronically infected (median 50.4, IQR 44.2–56.3 ml/min per 1.73 m2), and highest in those anti-HCV-negative (median 53.6, IQR 48.2–57.0 ml/min per 1.73 m2).
The results from a wide range of sensitivity analyses showed similar results. Of note, an analysis excluding those with F3/F4 or unknown liver fibrosis at baseline included 442 events during 52 085 PYFU (incidence of CKD 8.5/1000 PYFU; 95% CI 7.7–9.3) and showed similar results; albeit with wider confidence intervals. In this analysis, those anti-HCV-negative had significantly reduced rates of CKD (aIRR 0.65; 95% CI 0.47–0.89) compared with those cured, with no significant differences between other groups (left hand side; Fig. 2).
Our results were also consistent when we investigated separately HCV treatments including interferon or DAAs in those treated and cured or HCV-RNA-positive after treatment, with limited power in the latter analysis. There were 1068 events during 111 228 PYFU when DAA treatments were excluded from those cured or HCV-RNA-positive after treatment with an overall incidence rate of 9.6 (9.0–10.3), and the results are shown in the middle panel of Fig. 2. Similarly, when only including DAA treatments in those cured or HCV-RNA-positive after treatment, there were 1036 events during 105 291 PYFU, and the results are shown on the right hand side of Fig. 2. In this analysis, those anti-HCV-negative had significantly lower rates of CKD and those with spontaneous clearance had marginally lower rates of CKD compared with those cured.
Having a more stringent definition for CKD of a confirmed 25% decline in eGFR to less than 60 ml/min per 1.73 m2 resulted in a lower incidence of CKD (1001 events during 116 369 PYFU, rate 8.6/1000 PYFU; 95% CI 8.1–9.1), but also showed a lower incidence of CKD in those anti-HCV-negative), consistent with our main findings.
Characteristics of hepatitis C virus-treated persons at chronic kidney disease or last visit
Our final analysis focused further on those treated for HCV. Characteristics of persons at CKD or last visit for those not developing CKD are shown in Table 3. Of note, there was a much higher proportion of persons with ESLD in those cured who developed CKD, likely reflecting targeted treatment to those with most advanced liver disease when DAAs first became available. As would be expected, those cured had a much higher proportion of people who had received DAA treatment compared with those HCV-RNA-positive after treatment, regardless of whether they developed CKD or not.
This large study of almost 15 000 individuals with a median follow-up of approaching 7 years and with known anti-HCV and HCV-RNA status has found no reduction in CKD among those with cured HCV infection following treatment for HCV. To date, this is the largest study focused on CKD in HIV and HCV co-infected individuals comparing across HCV strata.
As previously reported by EuroSIDA and others [1,3,23], we found the lowest rates of CKD in those who were anti-HCV-negative or those with spontaneous clearance of HCV -RNA, as well as traditional factors associated with CKD, including age, hypertension, diabetes, and the use of potentially nephrotoxic antiretrovirals, as reported by many previous studies [24–26]. Cure of HCV with treatment has a number of benefits, including a reduction on both all cause and liver-related mortality . We were not able to demonstrate that HCV cure resulted in lower rates of CKD, consistent with previous studies [12–14], which had smaller populations and less power, or which considered decline in eGFR rather than CKD. Our study defined CKD rigorously using a confirmed eGFR less than 60 ml/min per 1.73 m2 over a period of 3 months. Slopes or rate of change in eGFR is arguably less clinically relevant than the definition used here. Our study also adjusted for a number of important confounding variables. HIV-associated nephropathy, membranous nephropathy, and membranoproliferative glomerulonephritis are sometimes found at biopsy in HIV and HCV coinfected persons [28–30] and more studies on the role of HIV-infection, HCV coinfection, HCV-RNA, and cure of HCV-RNA on these diseases is warranted. The role of HCV in extrahepatic comorbidities is not fully understood but may be related to the direct effect of HCV, immune activation, or indirect effects, such as drug and alcohol use .
In the pre-DAA era, there was some evidence in HCV monoinfected persons that interferon-based HCV treatment improved renal function and decreased the risk of CKD [31–33]. More recently, a study from Taiwan in monoinfected persons suggested a small decrease in renal function in persons treated with DAAs, although the changes were thought to be clinically insignificant . The results from previous studies are difficult to compare to our findings. Although some were large studies, not all had information on HCV treatment outcomes, baseline eGFR, predated the introduction of DAAs or included specific subgroups, such as those with cirrhosis. In addition, the contribution of different factors in coinfected individuals, including lifestyle factors, socioeconomic status, and mechanisms other than HCV replication, may play a role in the development of CKD [35–37].
We found the highest rates of CKD in those cured, although they were not significantly higher than those with chronic hepatitis C or those who were HCV-RNA-positive following HCV treatment. There are several possible reasons for our findings. Our study includes coinfected persons and follow-up to the middle of 2018. DAA treatment in EuroSIDA began to increase most notably around 2015 ; prior to this, it is likely that the healthiest persons were selected for interferon treatment. Following 2015, those with F3/F4 liver fibrosis and more advanced liver disease were prioritized for DAA treatment. Those cured were also less likely to reverse their CKD and the proportion of follow-up with an eGFR greater than 90 ml/min per 1.73 m2 was lowest, possibly suggesting a higher risk for renal disease. More of those cured developing CKD had a prior diagnosis of ESLD and those developing CKD in both those treated and cured and HCV-RNA-positive following treatment were more likely to have been treated with interferon and ribavirin. Although we have adjusted for a wide range of confounders, it is possible that our findings reflect confounding by indication and further follow-up of persons treated with new generation DAAs is warranted.
Our study has a number of limitations. First and foremost, our data are from a cohort study and while we have defined five distinct HCV strata based on single values of anti-HCV tests and HCV-RNA, comparisons across these strata are limited by our ability to adjust for differences as well as the possibility of unknown or unmeasured confounding that we cannot adjust for. We were not able to adjust for duration of HCV infection, which may be an important confounder. As in a previous study , we chose not to define SVR according to treatment guidelines  in part because of differences between the many centres in EuroSIDA in frequency of HCV-RNA monitoring following treatment. Persons HCV-RNA-positive after treatment may have only recently started treatment and with additional follow-up may be cured and move into this stratum. DAA regimens including sofosbuvir/ledipasvir and sofosbuvir/velpatasvir have been shown to increase the plasma concentration of tenofovir, especially when used with a boosted protease inhibitor , but we were not able to investigate an interaction between DAAs and tenofovir because of limited power. The strength of our study is that it is one of the largest of coinfected persons reported to date, with an extensive quality assurance and data monitoring program.
Although HCV-RNA-positive persons have previously been shown to have higher rates of CKD, curing HCV with HCV treatment was not associated with a lower rate of CKD in this study. Further long-term follow-up is required to investigate the role of DAAs as their use becomes widespread to determine if the higher rates seen in this study were because of underlying high risk of CKD and new DAAs being targeted at the sickest individuals.
The EuroSIDA study group:
The multi-centre study group, EuroSIDA (national coordinators in parenthesis).
Albania: (A Harxhi), University Hospital Center of Tirana, Tirana. Argentina: (M Losso), M Kundro, Hospital JM Ramos Mejia, Buenos Aires. Austria: (B Schmied), Otto Wagner Hospital, Vienna; R Zangerle, Medical University Innsbruck, Innsbruck. Belarus: (I Karpov), A Vassilenko, Belarus State Medical University, Minsk, VM Mitsura, Gomel State Medical University, Gomel; D Paduto, Regional AIDS Centre, Svetlogorsk. Belgium: (N Clumeck), S De Wit, M Delforge, Saint-Pierre Hospital, Brussels; E Florence, Institute of Tropical Medicine, Antwerp; L Vandekerckhove, University Ziekenhuis Gent, Gent. Bosnia-Herzegovina: (V Hadziosmanovic), Klinicki Centar Univerziteta Sarajevo, Sarajevo. 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: G Kronborg, T Benfield, Hvidovre Hospital, Copenhagen; J Gerstoft, T Katzenstein, Rigshospitalet, Copenhagen; C Pedersen, IS Johansen, Odense University Hospital, Odense; L Ostergaard, Skejby Hospital, Aarhus, L Wiese, NF Moller, Sjællands Universitetshospital, Roskilde; L N Nielsen, Hillerod Hospital, Hillerod. Estonia: (K Zilmer), West-Tallinn Central Hospital, Tallinn; Jelena Smidt, Nakkusosakond Siseklinik, Kohtla-Järve. Finland: (I Aho), Helsinki University Hospital, Helsinki. France: (J-P Viard), Hôtel-Dieu, Paris; P-M Girard, Hospital Saint-Antoine, Paris; C Pradier, E Fontas, Hôpital de l’Archet, Nice; C Duvivier, Hôpital Necker-Enfants Malades, Paris. Germany: (J Rockstroh), Universitäts Klinik Bonn; G Behrens, Medizinische Hochschule Hannover; O Degen, University Medical Center Hamburg-Eppendorf, Infectious Diseases Unit, Hamburg; HJ Stellbrink, IPM Study Center, Hamburg; C Stefan, JW Goethe University Hospital, Frankfurt; J Bogner, Medizinische Poliklinik, Munich; G. Fätkenheuer, Universität Köln, Cologne. Georgia: (N Chkhartishvili) Infectious Diseases, AIDS & Clinical Immunology Research Center, Tbilisi. Greece: (H Sambatakou), Ippokration General Hospital, Athens; G Adamis, N Paissios, Athens General Hospital “G Gennimatas”, Athens. Hungary: (J Szlávik), South-Pest Hospital Centre–National Institute for Infectology and Haematology, Budapest. Iceland: (M Gottfredsson), Landspitali University Hospital, Reykjavik. Ireland: (C Kelly), St. James's Hospital, Dublin. Israel: (L Tau), D Turner, M Burke, Ichilov Hospital, Tel Aviv; E Shahar, G Hassoun, Rambam Medical Center, Haifa; H Elinav, M Haouzi, Hadassah University Hospital, Jerusalem; D Elbirt, AIDS Center (Neve Or), Jerusalem. Italy: (A D’Arminio Monforte), Istituto Di Clinica Malattie Infettive e Tropicale, Milan; R Esposito, I Mazeu, C Mussini, Università Modena, Modena; F Mazzotta, A Gabbuti, Ospedale S Maria Annunziata, Firenze; A Lazzarin, A Castagna, N Gianotti, Ospedale San Raffaele, Milan; M Galli, A Ridolfo, Osp. L. Sacco, Milan. Lithuania: (V Uzdaviniene) Vilnius University Hospital Santaros Klinikos, Vilnius; R Matulionyte, Centro poliklinika, Vilnius, Vilnius University Hospital Santaros Klinikos, Vilnius. Luxembourg: (T Staub), R Hemmer, Centre Hospitalier, Luxembourg. Montenegro: (S Dragas), M Stevanovic, Clinical Center of Montenegro, Podgorica. Netherlands: (P Reiss), Academisch Medisch Centrum bij de Universiteit van Amsterdam, Amsterdam. North Macedonia (J Trajanovska), University Clinic for Infectious Diseases & Febrile Conditions, Mother Teresa 17, Skopje. Norway: (DH Reikvam), A Maeland, J Bruun, Oslo University Hospital, Ullevaal. Poland: (B Knysz), J Gasiorowski, M Inglot, Medical University, Wroclaw; E Bakowska, Centrum Diagnostyki i Terapii AIDS, Warsaw; R Flisiak, A Grzeszczuk, Medical University, Bialystok; M Parczewski, K Maciejewska, B Aksak-Was, Medical Univesity, Szczecin; M Beniowski, E Mularska, Osrodek Diagnostyki i Terapii AIDS, Chorzow; E Jablonowska, J Kamerys, K Wojcik, Wojewodzki Szpital Specjalistyczny, Lodz; I Mozer-Lisewska, B Rozplochowski, Poznan University of Medical Sciences, Poznan. Portugal: (A Zagalo), Hospital Santa Maria, Lisbon; K Mansinho, Hospital de Egas Moniz, Lisbon; F Maltez, Hospital Curry Cabral, Lisbon. Romania: (R Radoi), C Oprea, Carol Davila University of Medicine and Pharmacy Bucharest, Victor Babes Clinical Hospital for Infectious and Tropical Diseases, Bucharest. Russia: A Yakovlev, Medical Academy Botkin Hospital, St Petersburg; T Trofimora, Novgorod Centre for AIDS, Novgorod, I Khromova, Centre for HIV/AIDS & and Infectious Diseases, Kaliningrad; E Kuzovatova, Nizhny Novgorod Scientific and Research Institute of Epidemiology and Microbiology named after Academician I.N. Blokhina, Nizhny Novogrod; E Borodulina, E Vdoushkina, Samara State Medical University, Samara. Serbia: (J Ranin), The Institute for Infectious and Tropical Diseases, Belgrade. Slovenia: (J Tomazic), University Clinical Centre Ljubljana, Ljubljana. Spain: (JM Miro), JM Miró, M. Laguno, E. Martinez, F. Garcia, JL Blanco, M. Martinez-Rebollar, J. Mallolas, P Callau, J Rojas, A Inciarta, Hospital Clinic–IDIBAPS University of Barcelona, Barcelona; S Moreno, S. del Campo, Hospital Ramon y Cajal, Madrid; B Clotet, A Jou, R Paredes, J Puig, JM Llibre, JR Santos, Infectious Diseases Unit & IrsiCaixa AIDS Research Institute, Hospital germans Trias I Pujol, Badalona; P Domingo, M Gutierrez, G Mateo, MA Sambeat, Hospital Sant Pau, Barcelona; JM Laporte, Hospital Universitario de Alava, Vitoria-Gasteiz. Sweden: (K Falconer), A Thalme, A Sonnerborg, Karolinska University Hospital, Stockholm; CJ Treutiger, Venhälsan-Sodersjukhuset, Stockholm; L Flamholc, Malmö University Hospital, Malmö.Switzerland: (A Scherrer), R Weber, University Hospital Zurich; M Cavassini, University Hospital Lausanne; A Calmy, University Hospital Geneva; H Furrer, University Hospital Bern; M Battegay, University Hospital Basel; P Schmid, Cantonal Hospital St. Gallen. Ukraine: A Kuznetsova, Kharkov State Medical University, Kharkov; J Mikhalik, Crimean Republican AIDS centre, Simferopol; M Sluzhynska, Lviv Regional HIV/AIDS Prevention and Control CTR, Lviv.United Kingdom: A Milinkovic, St. Stephen's Clinic, Chelsea and Westminster Hospital, London; AM Johnson, E Simons, S Edwards, Mortimer Market Centre, London; A Phillips, MA Johnson, A Mocroft, Royal Free and University College Medical School, London (Royal Free Campus); C Orkin, Royal London Hospital, London; A Winston, Imperial College School of Medicine at St. Mary's, London; A Clarke, Royal Sussex County Hospital, Brighton; C Leen, Western General Hospital, Edinburgh.
The following centers have previously contributed data to EuroSIDA: Medical University, Gdansk, Poland Infectious Diseases Hospital, Sofia, Bulgaria Hôpital de la Croix Rousse, Lyon, France Hôpital de la Pitié-Salpétière, Paris, France Unité INSERM, Bordeaux, France Hôpital Edouard Herriot, Lyon, France Bernhard Nocht Institut für Tropenmedizin, Hamburg, Germany 1st I.K.A Hospital of Athens, Athens, Greece Ospedale Riuniti, Divisione Malattie Infettive, Bergamo, Italy Ospedale di Bolzano, Divisione Malattie Infettive, Bolzano, Italy Ospedale Cotugno, III Divisione Malattie Infettive, Napoli, Italy Dérer Hospital, Bratislava, Slovakia Hospital Carlos III, Departamento de Enfermedades Infecciosas, Madrid, Spain Kiev Centre for AIDS, Kiev, Ukraine Luhansk State Medical University, Luhansk, Ukraine Odessa Region AIDS Center, Odessa, Ukraine St Petersburg AIDS Centre, St Peterburg, Russia Infectology Centre of Latvia, Riga, Latvia University di Roma la Sapienza, Rome, Italy Istituto Nazionale Malattie Infettive Lazzaro Spallanzani, Rome, Italy
EuroSIDA Steering Committee
Steering Committee: I Karpov, M Losso, J Lundgren, J Rockstroh, I Aho, LD Rasmussen, V Svedhem, G Wandeler, C Pradier, N Chkhartishvili, R Matulionyte, C Oprea, JD Kowalska, J Begovac, JM Miró, G Guaraldi, R Paredes. Chair: G Wandeler Co-Chair: R Paredes. Study lead: A Mocroft.
Coordinating Centre Staff: O Kirk, L Peters, A Bojesen, D Raben, EV Hansen, D Kristensen, JF Larsen, AH Fischer.
Statistical Staff: A Mocroft, A Phillips, A Cozzi-Lepri, S Amele, A Pelchen-Matthews, A Roen
Funding: EuroSIDA was supported by the European Union's Seventh Framework Programme for research, technological development and demonstration under EuroCoord grant agreement no 260694. Current support includes unrestricted grants by ViiV Healthcare LLC, GlaxoSmithKline R&D Limited, Janssen Scientific Affairs, Janssen R&D, Bristol-Myers Squibb Company, Merck Sharp & Dohme Corp, Gilead Sciences. The participation of centres from Switzerland was supported by The Swiss National Science Foundation (Grant 148522). The study is also supported by a grant (grant number DNRF126) from the Danish National Research Foundation and by the International Cohort Consortium of Infectious Disease (RESPOND).
Conflicts of interest
There are no conflicts of interest.
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