JAIDS Journal of Acquired Immune Deficiency Syndromes:
Hepatitis C Virus Coinfection Does Not Influence the CD4 Cell Recovery in HIV-1-Infected Patients With Maximum Virologic Suppression
Peters, Lars MD*; Mocroft, Amanda PhD†; Soriano, Vincent MD, PhD‡; Rockstroh, Jürgen K MD§; Losso, Marcelo MD‖; Valerio, Laure MD¶; Aldins, Pauls MD#; Reiss, Peter MD, PhD**; Ledergerber, Bruno PhD††; Lundgren, Jens D MD, DMSc*‡‡; for the EuroSIDA Study Group
From the *Copenhagen HIV Programme, University of Copenhagen, Copenhagen, Denmark; †Research Department of Infection and Population Health, University College Medical School, Royal Free Campus, London, United Kingdom; ‡Hospital Carlos III, Madrid, Spain; §Department of Internal Medicine, University of Bonn, Bonn, Germany; ∥Hospital J.M. Ramos Mejia, Buenos Aires, Argentina; ¶CHU Nice Hôpital de L'Archet 1, Nice, France; #Infectology Center of Latvia, Riga, Latvia; **Academisch Medisch bij de Universiteit van Amsterdam, Amsterdam, The Netherlands; ††University Hospital, Zurich, Switzerland; and ‡‡Division of Infectious Diseases and Hospital Epidemiology, Centre for Viral Diseases/KMA, Rigshospitalet, Copenhagen, Denmark.
Received for publication June 29, 2008; accepted November 26, 2008.
The European Commission BIOMED 1 (CT94-1637), BIOMED 2 (CT97-2713), the 5th Framework (QLK2-2000-00773), and the 6th Framework (LSHP-CT-2006-018632) programs were the primary sponsors of the study. Unrestricted grants were also provided by Bristol-Myers-Squibb, GlaxoSmithKline, Roche, Gilead, Pfizer, Merck, Tibotec, and Boehringer-Ingelheim. The participation of centers from Switzerland was supported by a grant from the Swiss Federal Office for Education and Science.
Members of the EuroSIDA study group are listed in the appendix.
Correspondence to: Lars Peters, MD, Copenhagen HIV Programme, University of Copenhagen, Faculty of Health Sciences, The Panum Institute/Building 21.1, Blegdamsvej 3B, 2200 Copenhagen N, Denmark (e-mail: email@example.com).
Background: Conflicting data exist whether hepatitis C virus (HCV) affects the CD4 cell recovery in patients with HIV starting antiretroviral treatment.
Objective: To investigate the influence of HCV coinfection on the CD4 recovery in patients with maximum virologic suppression within the EuroSIDA cohort.
Methods: Patients tested for anti-HCV antibodies and with at least 2 consecutive HIV viral loads (VLs) <50 copies per milliliter after starting combination antiretroviral therapy were eligible for inclusion. For each pair of VL <50 copies per milliliter, the annual change in CD4 count was calculated and compared between (1) HCV-seronegative vs. HCV-seropositive patients, (2) HCV genotypes 1-4 in HCV-RNA+ patients, and (3) viremic vs. aviremic (HCV-RNA < 615 IU/mL) in HCV-seropositive patients. Results were adjusted for known confounders.
Results: Four thousand two hundred eight patients were included, representing 39,474 pairs of HIV VL measurements with VL <50 copies per milliliter and 12,492 person-years of follow-up. The unadjusted annual change in CD4 count for HCV-seropositive and HCV-seronegative patients was 35.5 cells per milliliter (95% confidence interval 27.2 to 43.9) and 38.3 cells per milliliter (95% confidence interval 34.8 to 41.9), respectively. After adjustment, there was no difference in CD4 change when comparing, according to HCV serostatus (P = 0.17), between genotypes (P = 0.23) or when comparing HCV viremic vs. aviremic patients (P = 0.57). Adjusting additionally for HCV treatment and HCV-RNA VL did not change the findings.
Conclusions: HCV serostatus did not influence the CD4 recovery in patients with HIV with maximum virologic suppression after starting combination antiretroviral therapy. Furthermore, no difference in CD4 gain was found when comparing distinct HCV genotypes in HCV-RNA+ patients or when comparing HCV viremic vs. aviremic HCV-seropositive patients.
Suppression of HIV viremia, recovery of CD4 T lymphocytes, and restoring immune function are the key events by which combination antiretroviral therapy (cART) provides clinical benefit to chronically HIV-infected persons.1 A large proportion of the approximately 2 million HIV-infected persons across the World Health Organization European region are coinfected with hepatitis C virus (HCV).2 It is controversial whether HCV coinfection influences the CD4 T-cell response to cART. Some observational studies have found that HIV/HCV-coinfected patients have an impaired CD4 cell recovery compared with HIV-monoinfected patients after initiating cART,3-9 whereas others have not found such an effect of HCV coinfection.2,10-12 Differences in adherence or potency of the drug regimens between the treatment groups could have contributed to the conflicting results of previous studies. Furthermore, most studies have defined HCV coinfection as the detection of antibodies toward this virus.2,4-11 Hence, the contribution of replicating HCV infection and the influence of HCV genotype on the CD4 cell response to ART have not been well studied.
Attempting to overcome potential confounders that could have influenced the results of previous studies, we aimed to assess the influence of chronic HCV coinfection and HCV genotype on the CD4 cell recovery in HIV-1-infected patients with persistent maximum virologic suppression (plasma HIV-RNA <50 copies/mL) within the EuroSIDA cohort.
PATIENTS AND METHODS
The EuroSIDA study is a prospective observational cohort study of 14,228 HIV-1-infected patients followed in 93 centers across Europe, Israel, and Argentina; detailed information about the study has been published elsewhere.1 Seven cohorts have been recruited to date, the first in May 1994, of 3108 patients, and the latest, of 2394 patients, was recruited from November 2005. At recruitment, in addition to demographic and clinical information, a complete antiretroviral (ARV) history was obtained, together with the 8 most recent CD4 counts and viral load (VL) measurements. VL was measured within each clinic according to local guidelines. This analysis includes data to a median date of November 2006.
Hepatitis C virus antibody (HCVAb) status has been collected since 1997 at the recruitment of cohort 3 and for all patients from cohorts 1 and 2 who were under follow-up at that time. The EuroSIDA plasma repository was set up in 1997 and collects plasma samples from all patients at 6 monthly intervals. The plasma samples are stored at minus 80°C. Patients with unknown HCVAb status and with a stored plasma sample were identified in 2006, and HCVAb status was determined. Patients who tested HCVAb+ were then tested for serum HCV-RNA and genotyped in a reference laboratory. In addition, patients recorded as HCVAb+ in the database but with unknown HCV genotype and stored samples were identified and tested for serum HCV-RNA and genotype.
HCV-RNA quantification was performed using the Versant HCV-RNA v3.0 assay (Bayer Diagnostics, Leverkusen, Germany), which has a linear dynamic range from 615 to 107 IU/mL. HCV genotyping was performed using the LiPA HCV genotype v2.0 assay (Innogenetics, Ghent, Belgium), which is a line probe assay that simultaneously detects sequences in the 5′-untranslated and core regions.
All patients from EuroSIDA who had started cART with at least 2 consecutive VLs <50 HIV-RNA copies per milliliter and known HCVAb status were eligible for inclusion. Patients were required to have a CD4 count measured in the 6 months before starting cART and distinct CD4 counts measured within 4 weeks (either side) of each VL measure (95% of CD4 counts were measured on the same date as VL measurements). cART was defined as a minimum of 3 ARVs of which at least 2 were nucleosides/nucleotides. Baseline (for descriptive purposes) was defined as the first VL <50 HIV-RNA copies per milliliter of 2 consecutive VLs <50 HIV-RNA copies per milliliter after starting cART at which a patient's hepatitis C status was known. The change in CD4 count occurring between each pair of consecutive VL <50 copies per milliliter was calculated and standardized for the time between VL measurements to give the annual change in the CD4 count. Pairs of VL measurements were excluded if any change (start or stop) in ARVs had been made between the 2 VL measurements.
Generalized linear models, using a normal distribution and an identity link function, with adjustments for repeated measures (as each patient could be included any number of times depending on their VL history) were used to describe CD4 count changes stratified by (1) HCV-seronegative vs. HCV-seropositive patients, (2) HCV genotypes 1-4 in HCV-RNA+ patients, and (3) viremic vs. aviremic (HCV-RNA < 615 IU/mL) in HCV-seropositive patients. Where patients had multiple VLs recorded within a 4-week period, the maximum VL in the 4-week period was used for analyses; similarly, patients with multiple CD4 counts measured within a 4-week period had the median of these values used.
In multivariable models, adjustments were made for factors previously demonstrated to be associated with change in CD4 counts in patients with VL <50 HIV-RNA copies per milliliter,12 age, time since cART initiation, change in CD4 counts since cART initiation, nucleoside pair, and third drug. The CD4 count before the pair used to calculate changes in CD4 counts was included in multivariable models to avoid regression to the mean and problems of overfitting. An additional adjustment was made for time between starting cART and initial virologic suppression (<500 copies/mL). All analyses were performed using SAS (Statistical Analysis Software, version 9.1; Cary, NC).
From 14,228 HIV-1-infected patients enrolled in EuroSIDA, 10,903 had started cART and 4803 had 2 consecutive VLs <50 HIV-RNA copies per milliliter with CD4 measured within 28 days of each VL. Of these, 4208 had known HCV serostatus and HCV-RNA and genotype measured in HCVAb+. Table 1 describes the baseline characteristics of the 4208 included patients; 822 patients (19.5%) were HCVAb+, and among them, 648 (78.8%) had detectable serum HCV-RNA. Overall, 332 (51.2%) were infected with HCV genotypes 1 and 27 (4.2%) and 201 (31.0%) and 88 (13.6%) with genotypes 2, 3, and 4, respectively.
When comparing HCVAb+ with HCVAb− patients, the HCVAb+ group was significantly younger (39.9 vs. 42.0 years), less likely to be male (68.9% vs. 79.4%), ARV naive at starting cART (35.8% vs. 49.1%) but more likely to be intravenous drug users (70.9% vs. 2.3%), to be of white race (88.4% vs. 84.3%), and HBsAg positive (7.1% vs. 5.9%). HCVAb+ patients had lower baseline and nadir CD4 counts (cells/μL) than HCVAb− patients (396 vs. 435 and 144 vs. 160, respectively), although there was no significant difference in CD4 counts when starting cART (208 vs. 216 cells/μL).
For all patients, the total time of follow-up with HIV-RNA <50 copies per milliliter was 12,492 person-years and the total number of VL measurements with HIV-RNA <50 copies per milliliter was 39,474 pairs. Median time between HIV-RNA pairs was 98 days (interquartile range 86-129 days), and median number of pairs per person was 7 (interquartile range 4-13 pairs).
Table 2 shows the summary of follow-up in the 3 comparison groups. Compared with the HCVAb− group, HCVAb+ patients had significantly shorter median follow-up with maximum suppressed HIV (27 vs. 32 months) and longer interval between VL measurements in a VL pair (105 vs. 98 days), but fewer number of VL pairs were included in analyses (6 vs. 8).
The most common nucleos(t)ide pair used was zidovudine/lamivudine, used in 16,498 VL pairs (41.7%), followed by lamivudine/stavudine, used in 6328 pairs (16.0%). Regimens most commonly included a nonnucleoside reverse transcriptase inhibitor used in 17,749 pairs (45.0%). For both nucleos(t)ide pairs and the third drug in the regimens, there were significant differences (P < 0.0001) between the groups, both when comparing HCV-seronegative vs. HCV-seropositive patients, within HCV genotypes and viremic vs. aviremic (Figs. 1A, B).
Figure 2A illustrates the crude unadjusted mean annual change in CD4 counts with maximum virologic suppression. In HCVAb+ patients, the mean annual increase in CD4 counts was 35.5 cells per year [95% confidence interval (CI) 27.2 to 43.9] vs. 38.3 cells per year (95% CI 34.8 to 41.9; P = 0.54) in HCV-seronegative patients. The mean annual CD4 change was similar for the other groups with no differences when comparing distinct HCV genotypes (genotypes 1-4) (P = 0.27) or when comparing those who were serum HCV-RNA+ with those who were HCVAb+/HCV-RNA negative (P = 0.58). Note the wide CIs around the annual change in CD4 counts, demonstrating both the wide variation in CD4 cell counts and also the comparatively small group sizes, especially for HCV genotypes 2 and 4.
Figure 2B shows the mean annual change in CD4 counts, after adjustment for nucleos(t)ide pair, third drug in regimen, age, change in CD4 count since starting cART, time since starting cART, time to initial HIV virologic suppression (<500 copies/mL), and whether the person was treatment naive at starting cART. HCVAb+ patients had a mean annual CD4 change of 30.4 cells per year (95% CI 21.8 to 39.1) vs. 37.3 cells per year (95% CI 33.7 to 40.8; P = 0.17) in HCV-seronegative patients. For the other comparisons, the results also differed very little from the unadjusted analysis. Again, there were no differences in the mean CD4 count change when comparing HCV genotypes (P = 0.23) or when comparing those who were HCV-RNA+ with those who had cleared the infection (P = 0.57).
In the comparison of HCV genotypes, adjusting additionally for HCV treatment and HCV-RNA level did not affect the findings (P = 0.39). HCV treatment was not significantly related to the change in CD4 counts (P = 0.99) nor was serum HCV-RNA level (P = 0.80). Also, in the comparison of those who had cleared HCV-RNA with those who had not, adjusting additionally for HCV treatment and HCV-RNA did not change the findings (P = 0.19). Neither HCV treatment (P = 0.98) nor HCV-RNA (P = 0.35) was related to the annual change in CD4 counts.
For all HCV-RNA+ patients, the mean adjusted CD4 increase in those with serum HCV-RNA >1 million IU/mL was 43.4 cells per year (95% CI 26.0 to 60.7) compared with an increase of 34.9 cells per year (95% CI 23.4 to 46.4) in those with serum HCV-RNA ≤1 million IU/mL (P = 0.43).
This study has examined the impact of HCV infection on the extent of CD4 recovery after initiation of cART in a large cohort of HIV-1-infected patients. Overall, no significant differences in CD4 gains were seen when comparing patients with and without HCVAb, HCV viremic vs. aviremic patients with HCVAb, and between distinct HCV genotypes among viremic patients.
An impaired CD4 T-cell recovery in HIV/HCV-coinfected patients initiating cART could affect the timing of cART initiation and broaden the indication for anti-HCV treatment. The issue has been investigated in several observational cohort studies over the past decade with conflicting results. Some studies have shown that coinfected patients have an impaired CD4 cell response after initiation of cART,3-9 whereas others found no effect of HCV coinfection on CD4 recovery.2,10-12 Because the HIV-HCV-coinfected population differs from the HIV-monoinfected population in many ways (eg, psychiatric disease, drug, and alcohol abuse),6,11,13,14 it is likely that different confounders, most importantly ART adherence, have contributed to the disparate findings of previous studies. In a subgroup of 1596 patients (33% HCVAb+) with HIV VL continuously below 400 copies per milliliter in the Swiss HIV Cohort Study, the authors still found that HCV-seropositive subjects had an impaired CD4 cell recovery compared with HCV-seronegative patients.6 However, it is possible that some patients still had low-level HIV replication that could have influenced the CD4 cell recovery. Interestingly, a more recent 4-year follow-up data from the Swiss HIV Cohort could not reproduce any difference in CD4 recovery when comparing HCV-seropositive and HCV-seronegative patients.15
In this large prospective cohort study, we provide evidence that HCV coinfection does not influence the CD4 cell recovery in HIV-1-infected patients who are persistently maximally HIV suppressed (VL < 50 HIV-RNA copies/mL) compared with HIV-monoinfected patients. We did not find any significant differences, in both the unadjusted and the adjusted models, when comparing HCV-seronegative vs. HCV-seropositive patients, when comparing HCV viremia and aviremia in HCV-seropositive patients, or when comparing distinct HCV genotypes in HCV-RNA+ patients, although the power of this latter analysis is limited as reflected in the wide CIs for HCV genotypes 2 and 4. Adjusting additionally for HCV treatment and serum HCV-RNA levels did not change the findings.
Importantly, our study differs from previous studies because we only have determined the CD4 cell increase when plasma HIV-RNA was persistently below 50 HIV-RNA copies per milliliter. Hence, we cannot evaluate the influence of HCV coinfection on the CD4 cell count in patients who are not fully HIV suppressed. However, this approach offers some clear advantages because it eliminates the influence of potential differences in ART adherence and drug potency between HCV-infected and HCV-uninfected patients.
Furthermore, we included only patients with well-characterized hepatitis C status in contrast to most other studies.2,4-11 Of 809 HCVAb+ patients included in our study, only 77% had detectable serum HCV-RNA. In the only other prospective cohort study also exclusively including patients with well-characterized HCV status, Antonucci et al3 found that HCV-RNA+ patients had a slower CD4 cell increase compared with HCV-seronegative patients after initiating cART. They also found that patients with HCV genotype 3 had a significantly reduced chance of achieving a CD4 cell increase of 300 cells per microliter, but no significant difference in the chance of achieving an increase of 200 cells per microliter, compared with patients with HCV genotype 1. However, in that study, there is no information about time to achievement of suppressed HIV-RNA after initiating cART. Hence, differences in adherence between the HCV-RNA+ group and the HCV-seronegative group could explain their findings. In the Swiss HIV Cohort, an explorative subanalysis also showed that HCV genotype 3 infection was significantly associated with an impaired CD4 recovery, defined as <50 cells per microliter after 1 year of successful cART.6 However, only 42 patients (14 genotype 3) were evaluated, limiting the power of this analysis. In our study, the median annual CD4 increase was also lower for patients with HCV genotype 3 compared with patients infected with other genotypes, in both the unadjusted and the adjusted analyses, although the differences were not statistically significant. It is possible that inclusion of more patients or longer follow-up could reveal significant differences between the groups, but with the present study, we can rule out large and clinically relevant differences.
A limitation of our study is the fact that some patients in the EuroSIDA cohort who have started cART had unknown hepatitis C status and did not have a plasma sample available. However, it is unlikely that the decision to send a sample for storage was related to HCV status. In addition, 2 different data sources were used, and therefore, potential biases might have been introduced. Where data were available from both the case report forms and the central laboratory, results from the central laboratory were used and taken as the most accurate results. Adjusting additionally for the data source did not alter our findings, which were also consistent when analyses were limited either to information provided on the case report form or to data provided by the central laboratory (data not shown).
In conclusion, in this EuroSIDA cohort study, we found that neither HCV viremia nor HCV genotype influences the CD4 cell recovery in HIV-1-infected patients with persistently HIV-RNA <50 copies per milliliter. It is possible that HIV/HCV-coinfected patients may still benefit from early initiation of cART because studies have shown that cART may slow fibrosis progression.16,17 Furthermore, HCV eradication will lower the risk of hepatotoxicity induced by ARV drugs18 and progression of liver disease.19,20
1. Mocroft A, Ledergerber B, Katlama C, et al. Decline in the AIDS and death rates in the EuroSIDA study: an observational study. Lancet
2. Rockstroh JK, Mocroft A, Soriano V, et al. Influence of hepatitis C virus infection on HIV-1 disease progression and response to highly active antiretroviral therapy. J Infect Dis
3. Antonucci G, Girardi E, Cozzi-Lepri A, et al. Role of hepatitis C virus (HCV) viremia and HCV genotype in the immune recovery from highly active antiretroviral therapy in a cohort of antiretroviral-naive HIV-infected individuals. Clin Infect Dis
4. Braitstein P, Zala C, Yip B, et al. Immunologic response to antiretroviral therapy in hepatitis C virus-coinfected adults in a population-based HIV/AIDS treatment program. J Infect Dis
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9. Weis N, Lindhardt BO, Kronborg G, et al. Impact of hepatitis C virus coinfection on response to highly active antiretroviral therapy and outcome in HIV-infected individuals: a nationwide cohort study. Clin Infect Dis
10. Sulkowski MS, Moore RD, Mehta SH, et al. Hepatitis C and progression of HIV disease. JAMA
11. Sullivan PS, Hanson DL, Teshale EH, et al. Effect of hepatitis C infection on progression of HIV disease and early response to initial antiretroviral therapy. AIDS
12. Yacisin K, Maida I, Ríos MJ, et al. Hepatitis C virus coinfection does not affect CD4 restoration in HIV-infected patients after initiation of antiretroviral therapy. AIDS Res Hum Retroviruses
13. Mocroft A, Phillips AN, Ledergerber B, et al. Relationship between antiretrovirals used as part of a cART regimen and CD4 cell count increases in patients with suppressed viremia. AIDS
14. Baillargeon JG, Paar DP, Wu H, et al. Psychiatric disorders, HIV infection and HIV/hepatitis co-infection in the correctional setting. AIDS Care
15. Kaufmann GR, Perrin L, Pantaleo G, et al. CD4 T-lymphocyte recovery in individuals with advanced HIV-1 infection receiving potent antiretroviral therapy for 4 years: the Swiss HIV Cohort Study. Arch Intern Med
16. Brau N, Salvatore M, Rios-Bedoya CF, et al. Slower fibrosis progression in HIV/HCV-coinfected patients with successful HIV suppression using antiretroviral therapy. J Hepatol
17. Verma S, Wang CH, Govindarajan S, et al. Do type and duration of antiretroviral therapy attenuate liver fibrosis in HIV-hepatitis C virus-coinfected patients? Clin Infect Dis
18. Labarga P, Soriano V, Vispo ME, et al. Hepatotoxicity of antiretroviral drugs is reduced after successful treatment of chronic hepatitis C in HIV-infected patients. J Infect Dis
19. Soriano V, Maida I, Nunez M, et al. Long-term follow-up of HIV-infected patients with chronic hepatitis C virus infection treated with interferon-based therapies. Antivir Ther
20. Rodriguez-Torres M, Rodriguez-Orengo JF, Rios-Bedoya CF, et al. Effect of hepatitis C virus treatment in fibrosis progression rate (FPR) and time to cirrhosis (TTC) in patients co-infected with human immunodeficiency virus: a paired liver biopsy study. J Hepatol
APPENDIX: THE EuroSIDA STUDY GROUP (NATIONAL COORDINATORS IN PARENTHESES)
Argentina: (M. Losso), A. Duran, Hospital J. M. Ramos Mejia, Buenos Aires. Austria: (N. Vetter) Pulmologisches Zentrum der Stadt Wien, Vienna. Belarus: (I. Karpov), A. Vassilenko, Belarus State Medical University, Minsk, V.M. Mitsura, Gomel State Medical University, Gomel; O. Suetnov, Regional AIDS Centre, Svetlogorsk. Belgium: (N. Clumeck) S. De Wit, B Poll, Saint-Pierre Hospital, Brussels; R. Colebunders, Institute of Tropical Medicine, Antwerp. Bulgaria: K. Kostov, Infectious Diseases Hospital, Sofia. Croatia: J. Begovac, University Hospital of Infectious Diseases, Zagreb. Czech Republic: (L. Machala) H. Rozsypal, Faculty Hospital Bulovka, Prague; D. Sedlacek, Charles University Hospital, Plzen. Denmark: (J. Nielsen) J. Lundgren, T. Benfield, O. Kirk, Hvidovre Hospital, Copenhagen; J. Gerstoft, T. Katzenstein, A.-B. E. Hansen, P. Skinhøj, Rigshospitalet, Copenhagen; C. Pedersen, Odense University Hospital, Odense; L. Oestergaard, 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; J. M. Livrozet, Hôpital Edouard Herriot, Lyon; P. Vanhems, University Claude Bernard, Lyon; C. Pradier, Hôpital de l'Archet, Nice; F. Dabis, 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; H. J. Stellbrink, IPM Study Center, Hamburg; S. Staszewski, J. W. 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. Sambattakou, Ippokration General 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: (A. Chiesi) 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 A. D. Cotugno, Monaldi Hospital, Napoli; G. Antonucci, F. Iacomi, P. Narciso, C. Vlassi, M. Zaccarelli, Istituto Nazionale Malattie Infettive Lazzaro Spallanzani, Rome; A. Lazzarin, R. Finazzi, 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) P. Aldins, 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: (J. Bruun) A. Maeland, V. Ormaasen, Ullevål Hospital, Oslo. Poland: (B. Knysz) J. Gasiorowski, Medical University, Wroclaw; A. Horban, Centrum Diagnostyki i Terapii AIDS, Warsaw; D. Prokopowicz, A. Wiercinska-Drapalo, Medical University, Bialystok; A. Boron-Kaczmarska, M. Pynka, Medical University, Szczecin; M. Beniowski, E. Mularska, Osrodek Diagnostyki i Terapii AIDS, Chorzow; H. Trocha, Medical University, Gdansk. Portugal: (F. Antunes) E. Valadas, 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; E. Vinogradova, St Petersburg AIDS Centre, St Petersburg; 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. Spain: (J. González-Lahoz) V. Soriano, L. Martin-Carbonero, P. Labarga, Hospital Carlos III, Madrid; B. Clotet, A. Jou, J. Conejero, C. Tural, Hospital Germans Trias i Pujol, Badalona; J. M. Gatell, J. M. Miró, Hospital Clinic i Provincial, Barcelona; P. Domingo, M. Gutierrez, G. Mateo, M. A. Sambeat, Hospital Sant Pau, Barcelona. Sweden: (A. Karlsson), Karolinska University Hospital, Stockholm; P. O. Persson, Karolinska University Hospital, Huddinge; 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. United Kingdom: (S. Barton) St. Stephen's Clinic, Chelsea and Westminster Hospital, London; A. M. Johnson, D. Mercey, Royal Free and University College London Medical School, London (University College Campus); A. Phillips, M. A. 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; R. Brettle, Western General Hospital, Edinburgh. Virology Group: B. Clotet (central coordinators) plus ad hoc virologists from participating sites in the EuroSIDA Study. Steering Committee: F. Antunes, B. Clotet, D. Duiculescu, J. Gatell, B. Gazzard, A. Horban, A. Karlsson, C. Katlama, B. Ledergerber (Chair), A. D'Arminio Montforte, A. Phillips, A. Rakhmanova, P. Reiss (Vice-Chair), J. Rockstroh. Coordinating Center Staff: J. Lundgren (project leader), O. Kirk, A. Mocroft, N. Friis-Møller, A. Cozzi-Lepri, W. Bannister, M. Ellefson, A. Borch, D. Podlekareva, J. Kjær, L. Peters, J. Reekie, J. Kowalska.
antiretroviral therapy; CD4; hepatitis; HIV; viral load
© 2009 Lippincott Williams & Wilkins, Inc.
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