Variable Impact on Mortality of AIDS-Defining Events Diagnosed during Combination Antiretroviral Therapy: Not All AIDS-Defining Conditions Are Created Equal

doi:10.1086/597468

Clin Infect Dis. Author manuscript; available in PMC 2011 February 2.

Published in final edited form as:

Clin Infect Dis. 2009 April 15; 48(8): 1138–1151.

doi: 10.1086/597468

PMCID: PMC3032444

NIHMSID: NIHMS264818

Variable Impact on Mortality of AIDS-Defining Events Diagnosed during Combination Antiretroviral Therapy: Not All AIDS-Defining Conditions Are Created Equal

Antiretroviral Therapy Cohort Collaboration (ART-CC)^a

Reprints or correspondence: Dr. Amanda Mocroft, Royal Free Centre for HIV Medicine and Research Dept. of Infection and Population Health, University College London Medical School, Royal Free Campus, Rowland Hill St, London, NW3 2PF, United Kingdom (Email: a.mocroft/at/pcps.ucl.ac.uk)

^aMembers of the writing committee are listed at the end of the text, and members of the study group are listed in the appendix.

The publisher's final edited version of this article is available free at Clin Infect Dis

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Abstract

Background

The extent to which mortality differs following individual acquired immunodeficiency syndrome (AIDS)–defining events (ADEs) has not been assessed among patients initiating combination antiretroviral therapy.

Methods

We analyzed data from 31,620 patients with no prior ADEs who started combination antiretroviral therapy. Cox proportional hazards models were used to estimate mortality hazard ratios for each ADE that occurred in >50 patients, after stratification by cohort and adjustment for sex, HIV transmission group, number of anti-retroviral drugs initiated, regimen, age, date of starting combination antiretroviral therapy, and CD4⁺ cell count and HIV RNA load at initiation of combination antiretroviral therapy. ADEs that occurred in <50 patients were grouped together to form a “rare ADEs” category.

Results

During a median follow-up period of 43 months (interquartile range, 19–70 months), 2880 ADEs were diagnosed in 2262 patients; 1146 patients died. The most common ADEs were esophageal candidiasis (in 360 patients), Pneumocystis jiroveci pneumonia (320 patients), and Kaposi sarcoma (308 patients). The greatest mortality hazard ratio was associated with non-Hodgkin’s lymphoma (hazard ratio, 17.59; 95% confidence interval, 13.84–22.35) and progressive multifocal leukoencephalopathy (hazard ratio, 10.0; 95% confidence interval, 6.70–14.92). Three groups of ADEs were identified on the basis of the ranked hazard ratios with bootstrapped confidence intervals: severe (non-Hodgkin’s lymphoma and progressive multifocal leukoencephalopathy [hazard ratio, 7.26; 95% confidence interval, 5.55–9.48]), moderate (cryptococcosis, cerebral toxoplasmosis, AIDS dementia complex, disseminated Mycobacterium avium complex, and rare ADEs [hazard ratio, 2.35; 95% confidence interval, 1.76–3.13]), and mild (all other ADEs [hazard ratio, 1.47; 95% confidence interval, 1.08–2.00]).

Conclusions

In the combination antiretroviral therapy era, mortality rates subsequent to an ADE depend on the specific diagnosis. The proposed classification of ADEs may be useful in clinical end point trials, prognostic studies, and patient management.

The reporting of unusual conditions, such as Kaposi sarcoma and Pneumocystis jiroveci pneumonia (PCP), among men who have sex with men signalled the arrival of HIV in the early 1980s [1, 2]. A definition for the new syndrome of AIDS was devised in 1985 [3]. The case definition was developed by epidemiologists with the aim of tracking the emerging epidemic. Changes to this surveillance case definition were made in 1987 and 1993, when additional opportunistic infections were added to the list of AIDS-defining events (ADEs) [4, 5]. Although the case definition of AIDS was never intended for this purpose, researchers adopted AIDS as an end point in clinical research, and clinicians used it as a prognostic marker. Indeed, before the advent of combination antiretroviral therapy (cART), patients who received a diagnosis of AIDS had a poor median survival of 12–18 months [6]. However, there was considerable variation in the duration of survival, depending on the specific diagnosis [7] and the CD4⁺ cell count at diagnosis [8].

In the era of cART, clinical trials have continued to use AIDS as a marker of clinical disease progression [9–11], although the low incidence of ADEs meant that many studies used changes in HIV load or CD4⁺ cell count, rather than the occurrence of AIDS or death, as their main end point. Large cohort studies and collaborations of cohorts used AIDS in prognostic models and risk scores to help clinicians, care providers, and patients to assess short-term and medium-term prognosis after initiating cART [12–14].

Studies that use AIDS as an end point or prognostic factor make an implicit assumption that all ADEs have the same consequence in terms of subsequent morbidity and mortality. To our knowledge, no study to date has had sufficient power to examine the variation in subsequent mortality associated with specific ADEs among patients receiving cART. We analyzed the large database of the Antiretroviral Therapy Cohort Collaboration (ART-CC) to determine the relative importance of different ADEs for subsequent mortality and to rank ADEs in terms of their prognostic importance for patients starting cART.

METHODS

ART-CC

The ART-CC is a collaboration of cohort studies from Europe and North America that was established in 2000 with the aim of describing the prognosis of antiretroviral-naive patients starting cART. The study design has been described in detail elsewhere [15]. In brief, prospective cohort studies were eligible if they had enrolled at least 100 patients with HIV infection aged ≥16 years who had not previously received antiretroviral treatment and who had started antiretroviral therapy with a combination of at least 3 drugs, including nucleoside reverse-transcriptase inhibitors, protease inhibitors, or non-nucleoside reverse-transcriptase inhibitors, with a median duration of follow-up of at least 1 year. Cohorts provided anonymized data on a predefined set of demographic, laboratory, and clinical variables, including age, sex, risk group, drugs included in the cART regimen, CD4⁺ cell count and viral load at cART initiation and at 6 and 36 months, in addition to the CD4⁺ cell count before the diagnosis of an ADE (each CD4⁺ cell count was measured within a maximum period of 6 months before the relevant time point).

Participating cohorts

Fifteen cohorts contributed data: the AIDS Therapy Evaluation Project Netherlands (3903 patients); the Aquitaine Cohort (831 patients); the British Columbia Centre for Excellence in HIV/AIDS (764 patients); Collaborations in HIV Outcomes Research (924 patients); the EuroSIDA study (92 centres across Europe, Argentina, and Israel; 1315 patients); the Frankfurt HIV Cohort (1436 patients); the French Hospital Database on HIV (13,758 patients); the Italian Cohort of Antiretroviral-Naive Patients (2428 patients); the Köln/Bonn Cohort (406 patients); the Proyecto para la Informatización del Seguimento Clínico-Epidemiológico de la Infección por HIV y SIDA (1851 patients); the Royal Free Hospital Cohort (649 patients); the Southern Alberta Clinic (270 patients); the Swiss HIV Cohort Study (2275 patients); the University of Alabama at Birmingham 1917 Clinic Cohort (485 patients); and the University of Washington HIV Cohort (322 patients). All cohorts have been approved by their local ethics committees or institutional review boards, use standardized methods of data collection, and schedule follow-up visits at least once every 6 months.

Inclusion criteria and definitions

All antiretroviral-naive patients with HIV infection who initiated cART before 31 December 2004 but who had not received a prior diagnosis of AIDS were included in analyses. Patient selection and data extraction were performed at the data centers of the participating cohorts. Anonymized data were pooled and analyzed centrally. ADEs were ascertained prospectively by use of the diagnostic criteria outlined in the 1993 AIDS definition [5]. Both definitive and presumptive diagnoses were included in analyses. Type-specific ADEs were combined into a single category; thus, cytomegalovirus retinitis and cytomegalovirus infection of other sites were combined into a single cytomegalovirus infection category. Different types of non-Hodgkin’s lymphoma (e.g., Burkitt’s lymphoma, primary brain lymphoma, immunoblastic lymphoma, and lymphoma of unknown histology) were also combined into a single category. ADEs that occurred in <50 patients in the combined dataset were grouped together to form a “rare ADEs” category and included coccidioidomycosis (1 diagnosis, 0 deaths), pulmonary candidiasis (15 diagnoses, 6 deaths), histoplasmosis (17 diagnoses, 4 deaths), invasive cervical carcinoma (20 diagnoses, 3 deaths), isosporiasis (7 diagnoses, 0 deaths), salmonella septicemia (7 diagnoses, 2 deaths), unspecified Centers for Disease Control and Prevention type C events (2 diagnoses, 1 death), unspecified tuberculosis (6 diagnoses, 1 death), and bacterial pneumonia (48 diagnoses, 5 deaths).

Statistical methods

Cox proportional hazards models, stratified by cohort and adjusted for sex, risk group, age, CD4⁺ cell count and viral load at cART initiation, cART regimen, and date of cART initiation were used to estimate the mortality hazard ratio (MHR) after each of the ADEs, compared with the MHR in patients who had not experienced an ADE. Each ADE was treated as a time-dependent covariate, and all ADEs were included in the model simultaneously. The proportional hazards assumption was tested, and there was no evidence of nonproportionality (P > .2). Recurrences of the same ADE were not included in analyses. Patients were followed up from the date of cART initiation until death (of any cause). All analyses were intent-to-treat, ignoring treatment interruptions or stopping of antiretroviral therapy. Patients who remained alive were censored at their last visit plus 50% of the median time between visits for each cohort. For example, if a cohort had a median of 6 months between follow-up visits, patients who did not die would be censored at the last visit plus 3 months. The hazard ratios for each ADE were ranked, and bootstrapping was used to derive 95% CIs for these ranks (on the basis of the 2.5th and 97.5th percentiles of ranks in 1000 resampled datasets). ADEs were split into 3 severity groups on the basis of these ranks, and the adjusted MHRs (aMHRs) for mild, moderate, and severe diagnoses were determined after additional adjustment for the number of ADEs diagnosed as a time-dependant covariate.

Patients starting cART may experience a rapid increase in their CD4⁺ cell count during the first 6 months of therapy [16], which will affect the subsequent risk of developing an ADE, and ADEs developing within the first 6 months of cART may be caused by immune reconstitution syndrome [17]. Therefore, we performed an additional analysis to estimate the risk of mortality following an ADE diagnosed after this initial period of treatment. Follow-up was censored at 6 months after cART initiation; patients with <6 months of follow-up were excluded, and ADEs that occurred during the initial 6 months after cART initiation were excluded. This analysis was adjusted as described above and was additionally adjusted for the CD4⁺ cell count and viral load determined at 6 months after cART initiation.

Statistical analyses were performed using SAS, version 9.1 (SAS). Bootstrapping was performed using Stata software, version 10.0 (StataCorp).

RESULTS

The characteristics of the 31,620 patients included in analyses are shown in table 1. Over a median follow-up period of 43 months (interquartile range [IQR], 19–70 months; 117,986 person-years of follow-up), 1146 patients (3.6%) died; of these patients, 377 died after an ADE. There were 2262 patients (7.2%) who received diagnoses of 2880 distinct ADEs. A total of 1745 (77.1%) of these 2262 patients received a diagnosis of 1 ADE during follow-up, 356 (15.7%) received diagnoses of 2 ADEs, 95 (4.2%) received diagnoses of 3 ADEs, and 22 (1.0%) received diagnoses of ≥4 ADEs. The most commonly diagnosed ADEs were esophageal candidiasis (360 diagnoses), Pneumocystis jiroveci (carinii) pneumonia (322 diagnoses), Kaposi sarcoma (308 diagnoses), pulmonary tuberculosis (257 diagnoses) and non-Hodgkin’s lymphoma (225 diagnoses).

Table 1

Demographic and clinical characteristics of 31,620 antiretroviral-naive patients starting combination antiretroviral therapy.

The CD4⁺ cell count at the time of diagnosis of each ADE (available for 2635 [91.5%] of the ADEs), was measured a median of 4 days before the ADE (IQR, 0–32 days). The median CD4⁺ cell count was 104 cells/μL (IQR, 32–247 cells), with 891 (33.8%) of the 2635 ADEs with available data occurring at a CD4⁺ cell count of ≤50 cells/μL, 924 (35.1%) occurring at 51–200 cells/μL, 412 (15.6%) occurring at 201–350 cells, 189 (7.2%) occurring at 351–500 cells/μL, and 219 (8.3%) occurring at >500 cells/μL. Figure 1 illustrates the CD4⁺ cell counts at diagnosis, stratified by the type of ADE. Non-Hodgkin’s lymphoma occurred at the highest median CD4⁺ cell count (204 cells/μL), with only 34 (16.4%) of the diagnoses made in patients with CD4⁺ cell counts ≤50 cells/μL. The viral load at diagnosis of each ADE (available for 1649 [57.3%] of the ADEs) was measured a median of 35 days before the ADE (IQR, 6–77 days). In total, 285 (17.3%) of the 1649 ADEs with available data occurred at viral loads <500 copies/mL, 154 (9.3%) occurred at 500–9999 copies/mL, and 1210 (73.4%) occurred at ≥10000 copies/mL. The distribution of the ADEs, stratified by viral load category at diagnosis, is shown in figure 2.

Figure 1

Median patient CD4⁺ cell count at diagnosis (interquartile range [IQR]) for each type of AIDS-defining event (ADE). COC, cryptococcosis; CMV, cytomegalovirus infection; DEM; AIDS dementia complex; ESO, esophageal candidiasis; HSD, herpes simplex disease; (more ...)

Figure 2

AIDS-defining events (ADEs) stratified by patient viral load at diagnosis of each type of ADE. COC, cryptococcosis; CMV, cytomegalovirus infection; DEM; AIDS dementia complex; ESO, esophageal candidiasis; HSD, herpes simplex disease; KSA, Kaposi’s (more ...)

The median time from initiation of cART to diagnosis of ADE was 9 months (IQR, 2–30 months); 1281 (44.5%), 317 (11.0%), 405 (14.1%), 495 (17.2%) and 382 (13.3%) of the ADEs occurred ≤6 months, 6–12 months, 12–24 months, 24–48 months, and >48 months after cART initiation, respectively. The median CD4⁺ cell count at diagnosis for ADEs that occurred ≤6 months after cART initiation (based on data available for 1269 [48.2%] of the ADEs) was slightly lower (86 cells/μL; IQR, 30–204 cells/μL) than that for ADEs that occurred after 6 months (129 cells/μL; IQR, 35–288 cells//μL). The majority of ADEs that were diagnosed within 6 months after cART initiation occurred in patients with viral loads ≥10,000 copies/mL (1048 [83.3%] of 1258 ADEs with data), whereas almost one-half of the ADEs diagnosed after 6 months occurred in patients with viral loads of <500 copies/mL (176 [45.0%] of 391 ADEs with data).

The aMHR associated with the diagnosis of any ADE was 3.45 (95% CI, 2.75–4.32). Figure 3 illustrates the aMHR associated with each ADE, ordered from the least severe to the most severe. At one end of the spectrum, there was little evidence for an increased risk of death associated with recurrent herpes simplex disease, with an aMHR of 1.09 (95% CI, 0.53–2.25). At the other end of the spectrum, a diagnosis of non-Hodgkin’s lymphoma was associated with an 18-fold increase in mortality (aMHR, 17.59; 95% CI, 13.84–22.35), whereas progressive multifocal leukoencephalopathy was associated with a 10-fold increase in mortality (aMHR, 10.00; 95% CI, 6.70–14.92). Cryptococcosis, cerebral toxoplasmosis, the group of rare ADEs, AIDS dementia complex, and disseminated Mycobacterium avium complex were the next most serious events, with aMHRs of 4–7. The ranks of the aMHR for each ADE, with bootstrapped 95% CIs, are shown in table 2. As would be expected, there was considerable sampling variability in the ranks, but 3 groups of ADEs could be identified: severe (non-Hodgkin’s lymphoma and progressive multifocal leukoencephalopathy), moderate (disseminated M. avium complex, AIDS dementia complex, rare ADEs, toxoplasmosis, and cryptococcosis), and mild (all other ADEs). The aMHR associated with any severe ADE was 7.26 (95% CI, 5.55–9.48), the aMHR associated with a moderate ADE was 2.35 (95% CI, 1.76–3.13), and the aMHR associated with a mild ADE was 1.47 (95% CI, 1.08–2.00).

Figure 3

Adjusted mortality hazard associated with each type of AIDS-defining event (ADE) after initiation of combination antiretroviral therapy (cART). The model was stratified by cohort and adjusted for age, sex, exposure group, number of drugs in the initial (more ...)

Table 2

Ranking and classification of AIDS-defining events (ADEs) according to severity (impact on subsequent mortality) in antiretroviral-naive patients initiating combination antiretroviral therapy.

There were some differences between the ADEs in terms of the proportion of diagnoses that occurred within the initial 6 months of cART (table 3), ranging from 30.8% for esophageal candidiasis to 61.6% for disseminated M. avium complex. Table 3 also presents the aMHR after the initial 6 months of cART, adjusted additionally for the CD4⁺ cell count and viral load at 6 months after cART initiation and taking account of the initial response to cART. Although 95% CIs are wider because of the reduced number of ADEs, patterns of mortality are similar to those seen in figure 3 and table 2.

Table 3

Number of AIDS-defining events (ADEs) and deaths overall and within the first 6 months after initiation of combination antiretroviral therapy (cART) and adjusted mortality hazard ratios (aMHRs) associated with ADEs diagnosed after 6 months of therapy (more ...)

DISCUSSION

AIDS was first defined in the 1980s for surveillance purposes. However, in the era of cART, AIDS continues to be used as a composite outcome in clinical research and a prognostic marker in routine clinical care. Clinical trials that use outcome data assume that all ADEs have similar impacts on survival. The analyses presented here, which are based on >31,000 patients and almost 3000 ADEs, demonstrate substantial variation both in the median CD4⁺ cell count at diagnosis of different ADEs and in the relative hazard of death after the diagnosis. We identified 3 groups of ADEs, based on the prognosis after diagnosis: severe ADEs, which are associated with a substantial increase in the risk of death; ADEs with a moderate impact on subsequent mortality; and mild ADEs, which have a relatively small influence on subsequent mortality.

The large size of the collaborative database, which includes patients treated in different settings in countries from Europe and North America, is a strength of this study. ADEs were ranked before the widespread introduction of cART [18, 19], but to our knowledge, this is the first study with sufficient power to enable most ADEs to be compared only among patients who have started cART. Previous studies that have considered survival after an initial ADE included only those patients who received a diagnosis of an ADE and included a significant proportion of patients who received a diagnosis of AIDS between 1990 and 1995 (when the widespread introduction of cART occurred) [20–22] or who received a diagnosis before cART became widely available [23]. This analysis thus makes an important contribution to defining the prognosis of patients who developed an ADE while receiving cART. Such information is of obvious importance to patients and their health care providers and is required to monitor and predict the progress of the epidemic, as well as to plan health services in the era of cART [24].

The initial immunologic response to cART is important for predicting prognosis after cART initiation [25]; in this study, ADEs diagnosed within 6 months after cART initiation typically occurred at slightly lower CD4⁺ cell counts than did ADEs that were diagnosed >6 months after cART initiation, which is consistent with the recovery of immune function subsequent to starting cART. The so-called immune reconstitution inflammatory syndrome occurs when the immune system begins to respond to preexisting opportunistic disorders that were present before initiation of antiretroviral therapy [26]. We have also presented the aMHRs, both from the time of cART initiation and from after the initial 6 months of therapy. In different circumstances, it may be appropriate to use either the post-cART initiation data (which represents a combination of immunocompromise, disease severity, and treatment effectiveness) or the pre-cART initiation data (which generally reflects untreated or poorly treated ADEs and, therefore, represents immunocompromise more specifically).

The use of composite end points, such as AIDS, in clinical trials can be advantageous: combined end points result in higher event rates, which translate into a smaller sample size, shorter trial duration, or greater precision of estimates; disease progression can then be measured either as progression to any ADE or progression to a more serious ADE. Composite end points could also be used as a predefined secondary end point or incorporated into sensitivity analyses. However, the validity of composite end points rests on the assumption that patients and clinicians attach a similar importance to the different components and that these components will be affected in similar ways by interventions [27–29]. Combining different ADEs as a single event means that important prognostic information is lost. Although the groupings proposed here were assigned post hoc, our results confirm the findings of previous smaller studies that integrated the severity of an ADE into ranking systems [30, 31], rather than treating all ADEs equally. It is also worth noting that the ranking of the diseases in the cART treatment era matches well with the ranking of diagnoses made before the widespread introduction of cART [32]. Although our classification by severity overcomes some of the drawbacks of the composite end point AIDS, what we propose are 3 composite outcomes that include a varying number of ADEs that have a similar impact on mortality. From the perspective of patients, ADEs continue to differ in important ways within the same prognostic group. For example, within the group of ADEs associated with moderately increased risk of death, AIDS dementia complex may well be judged to be more severe than the other events in this group. Similarly, it seems unlikely that the biologically diverse conditions within each group will be affected in the same way by antiretroviral drugs or other interventions.

There are some limitations to this study. Patients who died after an ADE may not have died of causes that were directly associated with the ADE that was diagnosed. The ART-CC is currently collecting information on causes of death for all patients and is using this information to categorize causes of death when possible. Preliminary data suggest that, of those patients whose cause of death could be classified, ~40% died of AIDS. The major non-AIDS causes of death among these patients were non–AIDS–defining malignancies, violent causes (including suicide and substance abuse), heart disease, and liver disease. Detailed information on the causes of death among ART-CC patients will be presented in a separate article.

The ART-CC does not collect information on coinfections, such as hepatitis, cardiovascular disease, non–AIDS-defining malignancies, or liver disease, that also contribute to mortality [33–35]. We were not able to adjust for immunodeficiency or treatment interruptions throughout the follow-up period; however, the risk of death among HIV-infected patients increases as the CD4⁺ cell count decreases [36, 37]. Results were similar when the initial response to cART was taken into account by adjusting for CD4⁺ cell count and HIV RNA level at 6 months after initiation of therapy. The data were from a number of cohorts, and there is some variation in the ascertainment of ADEs. This analysis focused on the first ADE experienced after cART initiation, and the rankings could vary if recurrences were included. Finally, despite the large size of the collaborative cohort, the number of some types of ADEs was too small to allow separate analyses of these events.

In conclusion, in the cART era, mortality rates after an ADE depend on the specific ADE diagnosed, and not all ADEs are created equal. The severity of ADEs should be considered in clinical trials with clinical end points and in future prognostic models, as well as in patient management. Similar studies are required in lower-income settings, where cART is increasingly used but where outcomes differ from those observed in industrialized settings [38].

ART-CC WRITING COMMITTEE

Amanda Mocroft (Research Department of Infection and Population Health, University College London Medical School, Royal Free Campus, London, United Kingdom), Jonathan A. C. Sterne (Department of Social Medicine, University of Bristol, Bristol, United Kingdom), Matthias Egger (Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland) Margaret May (Department of Social Medicine, University of Bristol, Bristol, United Kingdom), Sophie Grabar (Institut National de la Santé et de la Recherche Médicale [INSERM] U720, Universitè Paris Descartes, Facultè de Mèdecine, Paris, France), Hansjakob Furrer (Division of Infectious Diseases, Bern University Hospital and University of Bern, Bern, Switzerland), Caroline Sabin (Research Department of Infection and Population Health, University College London Medical School, Royal Free Campus, London, United Kingdom), Gerd Fatkenheuer (Department of Internal Medicine, University of Cologne, Cologne, Germany), Amy Justice (Yale University School of Medicine, New Haven, and Veterans Affairs Connecticut Healthcare System, West Haven, Connecticut), Peter Reiss (Academisch Medisch Centrum bij de Universiteit van Amsterdam, Amsterdam, The Netherlands), Antonella d’Arminio Monforte (Clinic of Infectious Diseases and Tropical Medicine, “San Paolo” Hospital, University of Milan, Italy), John Gill (Division of Infectious Diseases, University of Calgary, Calgary, Canada), Robert Hogg (Division of Epidemiology and Population Health, British Columbia Centre for Excellence in HIV/AIDS, Vancouver, Canada), Fabrice Bonnet (INSERM U593, Université Victor Segalen Bordeaux, Bordeaux, France), Mari Kitahata (Department of Medicine, University of Washington, Seattle, United States), Schlomo Staszewski (Zentrum der Inneren Medizin, J. W. Goethe Universität, Frankfurt, Germany), Jordi Casabona (Centre d’Estudis Epidemiològics sobre la Sida de Catalunya, Badalona, Barcelona, Spain), Ross Harris (Department of Social Medicine, University of Bristol, Bristol, United Kingdom), and Michael Saag (Division of Infectious Disease, Department of Medicine, University of Alabama at Birmingham, Birmingham, United States).

Acknowledgments

Financial support. The ART-CC is supported by the UK Medical Research Council (G0700820). Sources of funding of individual cohorts include the Agence Nationale de Recherche contre le SIDA; the Institut National de la Santé et de la Recherche Médicale; the French, Italian, and Swiss Ministries of Health; the Stichting HIV Monitoring; the European Commission; the British Columbia and Alberta Governments; the Michael Smith Foundation for Health Research; the Canadian Institutes of Health Research; and unrestricted grants from GlaxoSmithKline, Roche, and Böehringer-Ingelheim.

APPENDIX. THE ANTIRETROVIRAL THERAPY COHORT COLLABORATION STUDY GROUP

STEERING COMMITTEE

Jordi Casabona (Proyecto para la Informatización del Seguimento Clínico-Epidemiológico de la Infección por HIV y SIDA [PISCIS] Cohort), Geneviève Chêne (Aquitaine Cohort), Dominique Costagliola (French Hospital Database on HIV [FHDH]), François Dabis (Aquitaine Cohort), Antonella D’Arminio Monforte (Italian Cohort of Antiretroviral-Naive Patients [ICONA]), Frank de Wolf (AIDS Therapy Evaluation Project Netherlands [ATHENA]), Matthias Egger (Swiss HIV Cohort Study [SHCS]), Gerd Fatkenheuer (Köln/Bonn Cohort), John Gill (Southern Alberta Clinic), Robert Hogg (British Columbia Centre for Excellence in HIV/AIDS [BCCfE-HIV]), Amy Justice (Veterans Affairs Connecticut Healthcare System), Mari Kitahata (University of Washington HIV Cohort), Bruno Ledergerber (SHCS), Amanda Mocroft (EuroSIDA), Andrew Phillips (EuroSIDA), Peter Reiss (ATHENA), Michael Saag (University of Alabama at Birmingham 1917 Clinic Cohort), Caroline Sabin (Royal Free Hospital Cohort), Schlomo Staszewski (Frankfurt HIV Cohort), Ian Weller.

COORDINATING TEAM

Matthias Egger, Margaret May, Ross Harris, and Jonathan Sterne (principal investigator).

FHDH

Scientific committee

S. Abgrall, F. Barin, M. Bentata, E. Billaud, F. Boué, C. Burty, A. Cabié, D. Costagliola, L. Cotte, P. De Truchis, X. Duval, C. Duvivier, P. Enel, L. Fredouille-Heripret, J. Gasnault, C. Gaud, J. Gilquin, S. Grabar, C. Katlama, M. A. Khuong, J. M. Lang, A. S. Lascaux, O. Launay, A. Mahamat, M. Mary-Krause, S. Matheron, J. L. Meynard, J. Pavie, G. Pialoux, F. Pilorgé, I. Poizot-Martin, C. Pradier, J. Reynes, E. Rouveix, A. Simon, P. Tattevin, H. Tissot-Dupont, J. P. Viard, and N. Viget.

DMI2 coordinating center

French Ministry of Health (A. Pariente-Khayat and Valérie Salomon), Technical Hospitalization Information Agency (N. Jacquemet and A. Rivet).

Statistical analysis center

INSERM U720 (S. Abgrall, D. Costagliola, S. Grabar, M. Guiguet, I. Kousignian, E. Lanoy, L. Lièvre, M. Mary-Krause, V. Potard, H. Selinger-Leneman).

CISIH (Paris area)

CISIH de Bichat-Claude Bernard (Hôpital Bichat-Claude Bernard: E. Bouvet, B. Crickx, J. L. Ecobichon, C. Leport, S. Matheron, C. Picard-Dahan, P. Yeni), CISIH de Paris-Centre Ouest (Hôpital Européen Georges Pompidou: D. Tisne-Dessus, L. Weiss; GH Tarnier-Cochin: D. Salmon, D. Sicard; Hôpital Saint-Joseph: I. Auperin, J. Gilquin; Hôpital Necker adultes: L. Roudière, J. P. Viard), CISIH de Paris-Sud (Hôpital Antoine Béclère: F. Boué, R. Fior; Hôpital de Bicêtre: J. F. Delfraissy, C. Goujard; Hôpital Henri Mondor: C. Jung, P. Lesprit; Hôpital Paul Brousse), CISIH de Paris-Est (Hôpital Saint-Antoine: N. Desplanque, J. L. Meynard, M. C. Meyohas, O. Picard; Hôpital Tenon: J. Cadranel, C. Mayaud, G. Pialoux), CISIH de Pitié-Salpétrière (GH Pitié-Salpétrière: F. Bricaire, S. Herson, C. Katlama, A. Simon), CISIH de Saint-Louis (Hôpital Saint-Louis: J. P. Clauvel, J. M. Decazes, L. Gerard, J. M. Molina; GH Lariboisière-Fernand Widal: M. Diemer, P. Sellier), CISIH 92 (Hôpital Ambroise Paré: H. Berthé, C. Dupont; Hôpital Louis Mourier: C. Chandemerle, E. Mortier; Hôpital Raymond Poincaré: P. de Truchis), CISIH 93 (Hôpital Avicenne: M. Bentata, P. Honoré; Hôpital Jean Verdier: V. Jeantils, S. Tassi; Hôpital Delafontaine: D. Mechali, B. Taverne).

CISIH (outside Paris area)

CISIH Auvergne-Loire (CHU de Clermont-Ferrand: F. Gourdon, H. Laurichesse; CHRU de Saint-Etienne: A. Fresard, F. Lucht); CISIH de Bourgogne-Franche Comté (CHRU de Besançon; CHRU de Dijon; CH de Belfort: P. Eglinger, J. P. Faller; CHRU de Reims); CISIH de Caen (CHRU de Caen: C. Bazin, R. Verdon), CISIH de Grenoble (CHU de Grenoble), CISIH de Lyon (Hôpital de la Croix-Rousse: A. Boibieux, D. Peyramond; Hôpital Edouard Herriot: J. M. Livrozet, J. L. Touraine; Hôtel-Dieu: L. Cotte, C. Trepo), CISIH de Marseille (Hôpital de la Conception: I. Ravaux, H. Tissot-Dupont; Hôpital Nord: J. P. Delmont, J. Moreau; Institut Paoli Calmettes: J. A. Gastaut; Hôpital Sainte-Marguerite: I. Poizot-Martin, F. Retornaz, J. Soubeyrand; CHG d’Aix-En-Provence: T. Allegre, P. A. Blanc; Centre pénitentiaire des Baumettes: A. Galinier, J. M. Ruiz; CH d’Arles; CH d’Avignon: G. Lepeu; CH de Digne Les Bains: P. Granet-Brunello; CH de Gap: J. P. Esterni, L. Pelissier; CH de Martigues: R. Cohen-Valensi, M. Nezri; CHI de Toulon: S. Chadapaud, A. Laffeuillade), CI-SIH de Montpellier (CHU de Montpellier: J. Reynes; CHG de Nîmes), CISIH de Nancy (Hôpital de Brabois: T. May, C. Rabaud), CISIH de Nantes (CHRU de Nantes: E. Billaud, F. Raffi), CISIH de Nice (Hôpital Archet 1: P. Pugliese, C. Pradier; CHG Antibes Juan les Pins), CISIH de Rennes (CHU de Rennes: C. Arvieux, C. Michelet), CISIH de Rouen (CHRU de Rouen: F. Borsa-Lebas, F. Caron), CISIH de Strasbourg (CHRU de Strasbourg: P. Fraisse, J. M. Lang, D. Rey; CH de Mulhouse), CISIH de Toulouse (CHU Purpan: E. Arlet-Suau, L. Cuzin, P. Massip, M. F. Thiercelin Legrand; Hôpital la Grave; CHU Rangueil), CISIH de Tourcoing-Lille (CH Gustave Dron; CH de Tourcoing: Y. Yasdanpanah), CISIH de Tours (CHRU de Tours; CHU Trousseau).

Overseas

CISIH de Guadeloupe (CHRU de Pointe-à-Pitre), CISIH de Guyane (CHG de Cayenne: R. Pradinaud, M. Sobesky), CISIH de Martinique (CHRU de Fort-de-France), CI-SIH de La Réunion (CHD Félix Guyon: C. Gaud, M. Contant).

ICONA

Italy

Ancona: M. Montroni, G. Scalise, M. C. Braschi, A. Riva. Aviano (PN): U. Tirelli, F. Martellotta. Bari: G. Pastore, N. Ladisa. Bergamo: F. Suter, C. Arici. Bologna: F. Chiodo, V. Colangeli, C. Fiorini. Brescia: G. Carosi, G. Cristini, C. Torti, C. Minardi, D. Bertelli. Busto Arsizio: T. Quirino. Cagliari: P. E. Manconi, P. Piano. Catanzaro: L. Cosco, A. Scerbo. Chieti: J. Vecchiet, M. D’Alessandro. Como: D. Santoro, L. Pusterla. Cremona: G. Carnevale, S. Lorenzotti. Cuggiono: P. Viganò, M. Mena. Ferrara: F. Ghinelli, L. Sighinolfi. Firenze: F. Leoncini, F. Mazzotta, M. Pozzi, S. Lo Caputo. Foggia: B. Grisorio, S. Ferrara. Galatina (LE): P. Grima, P. F. Grima. Genova: G. Pagano, G. Cassola, A. Alessandrini, R. Piscopo. Grosseto: M. Toti, M. Trezzi. Latina: F. Soscia, L. Tacconi. Lecco: A. Orani, P. Perini. Lucca: A. Scasso, A. Vincenti. Macerata: F. Chiodera, P. Castelli. Mantova: A. Scalzini, L. Palvarini. Milano: M. Moroni, A. Lazzarin, G. Rizzardini, L. Caggese, A. d’Arminio Monforte, P. Cicconi, A. Galli, S. Merli, C. Pastecchia, M. C. Moioli. Modena: R. Esposito, C. Mussini. Napoli: N. Abrescia, A. Chirianni, C. M. Izzo, M. Piazza, M. De Marco, R. Viglietti, E. Manzillo, S. Nappa. Palermo: A. Colomba, V. Abbadessa, T. Prestileo, S. Mancuso. Parma: C. Ferrari, P. Pizzaferri. Pavia: G. Filice, L. Minoli, R. Bruno, S. Novati. Perugia: F. Baldelli, G. Camanni. Pesaro: E. Petrelli, A. Cioppi. Piacenza: F. Alberici, A. Ruggieri. Pisa: F. Menichetti, C. Martinelli. Potenza: C. De Stefano, A. La Gala. Ravenna: G. Ballardini, E. Rizzo. Reggio Emilia: G. Magnani, M. A. Ursitti. Rimini: M. Arlotti, P. Ortolani. Roma: R. Cauda, F. Dianzani, G. Ippolito, A. Antinori, G. Antonucci, M. Ciardi, P. Narciso, N. Petrosillo, V. Vullo, A. De Luca, M. Zaccarelli, R. Acinapura, P. De Longis, M. P. Trotta, P. Noto, M. Lichtner, M. R. Capobianchi, F. Carletti, E. Girardi, P. Pezzotti, G. Rezza. Sassari: M. S. Mura, M. Mannazzu. Torino: P. Caramello, G. Di Perri, G. C. Orofino, M. Sciandra. Varese: P. A. Grossi, C. Basilico. Verbania: A. Poggio, G. Bottari. Venezia: E. Raise, F. Ebo. Vicenza: G. Pellizzer, D. Buonfrate. Taranto: F. Resta, K. Loso.

United Kingdom

London: A. Cozzi Lepri.

SHCS

M. Battegay, E. Bernasconi, J. Böni, H. Bucher, P. Bürgisser, S. Cattacin, M. Cavassini, R. Dubs, M. Egger, L. Elzi, P. Erb, M. Fischer, M. Flepp, A. Fontana, P. Francioli (President of the SHCS, Centre Hospitalier Universitaire Vaudois, CH-1011-Lausanne), H. Furrer (Chairman of the Clinical and Laboratory Committee), M. Gorgievski, H. Günthard, H. Hirsch, B. Hirschel, I. Hösli, C. Kahlert, L. Kaiser, U. Karrer, C. Kind, T. Klimkait, B. Ledergerber, G. Martinetti, B. Martinez, N. Müller, D. Nadal, M. Opravil, F. Paccaud, G. Pantaleo, M. Rickenbach (Head of Data Center), C. Rudin (Chairman of the Mother and Child Substudy), P. Schmid, D. Schultze, J. Schüpbach, R. Speck, P. Taffé, P. Tarr, A. Telenti, A. Trkola, P. Vernazza (Chairman of the Scientific Board), R. Weber, S. Yerly.

ATHENA

L. A. Gras (biostatistician), A. I. van Sighem (senior researcher), C. Smit (epidemiologist), F. de Wolf (director).

Treating physicians

W. Bronsveld, M. E. Hillebrand-Haverkort, Medisch Centrum Alkmaar; J. M. Prins, J. Branger, J. K. M. Eeftinck Schattenkerk, J. Gisolf, M. H. Godfried, J. M. A. Lange, K. D. Lettinga, J. T. M. van der Meer, F. J. B. Nellen, T. van der Poll, P. Reiss, T. A. Ruys, R. Steingrover, J. N. Vermeulen, S. M. E. Vrouenraets, M. van Vugt, F. W. M. N. Wit, Academisch Medisch Centrum bij de Universiteit van Amsterdam; T. W. Kuijpers, D. Pajkrt, H. J. Scherpbier, Emma Kinderziekenhuis-AMC, Amsterdam; A. van Eeden, St. Medisch Centrum Jan van Goyen, Amsterdam; K. Brinkman, G. E. L. van den Berk, W. L. Blok, P. H. J. Frissen, J. C. Roos, W. E. M. Schouten, Onze Lieve Vrouwe Gasthuis, Amsterdam; J. W. Mulder, E. C. M. van Gorp, J. Wagenaar, Slotervaart Ziekenhuis, Amsterdam; J. Veenstra, St. Lucas Andreas Ziekenhuis, Amsterdam; S. A. Danner, M. A. Van Agtmael, F. A. P. Claessen, R. M. Perenboom, A. Rijkeboer, M. G. A. van Vonderen, VU Medisch Centrum, Amsterdam; C. Richter, J. van der Berg, Ziekenhuis Rijnstate, Arnhem; R. Vriesendorp, F. J. F. Jeurissen, Medisch Centrum Haaglanden, locatie Westeinde, Den Haag; R. H. Kauffmann, K. Pogány, Haga Ziekenhuis, locatie Leyenburg, Den Haag; B. Bravenboer, Catharina Ziekenhuis, Eindhoven; C. H. H. ten Napel, G. J. Kootstra Medisch Spectrum Twente, Enschede; H. G. Sprenger, S. van Assen, J. T. M. van Leeuwen, Universitair Medisch Centrum, Groningen; R. Doedens, E. H. Scholvinck, Universitair Medisch Centrum, Beatrix kliniek, Groningen; R. W. ten Kate, R. Soetekouw, Kennemer Gasthuis, Haarlem; D. van Houte, M. B. Polée, Medisch Centrum Leeuwarden; F. P. Kroon, P. J. van den Broek, J. T. van Dissel, E. F. Schippers, Leids Universitair Medisch Centrum, Leiden; G. Schreij, S. van der Geest, S. Lowe, A. Verbon, Academisch Ziekenhuis Maastricht; P. P. Koopmans, R. Van Crevel, R. de Groot, M. Keuter, F. Post, A. J. A. M. van der Ven, A. Warris, Universitair Medisch Centrum St. Radboud, Nijmegen; M. E. van der Ende, I. C. Gyssens, M. van der Feltz, J. L. Nouwen, B. J. A. Rijnders, T. E. M. S. de Vries, Erasmus Medisch Centrum, Rotterdam; G. Driessen, M. van der Flier, N. G. Hartwig, Erasmus Medisch Centrum, Sophia, Rotterdam; J. R. Juttman, M. E. E. van Kasteren, C. Van de Heul, St. Elisabeth Ziekenhuis, Tilburg; I. M. Hoepelman, M. M. E. Schneider, M. J. M. Bonten, J. C. C. Borleffs, P. M. Ellerbroek, C. A. J. J. Jaspers, T. Mudrikove, C. A. M. Schurink, E. H. Gisolf, Universitair Medisch Centrum Utrecht; S. P. M. Geelen, T. F. W. Wolfs, T. Faber, Wilhelmina Kinderziekenhuis-UMC, Utrecht; A. A. Tanis, Ziekenhuis Walcheren, Vlissingen; P. H. P. Groeneveld, Isala Klinieken, Zwolle; J. G. den Hollander, Medisch Centrum Rijnmond Zuid, locatie Clara, Rotterdam; A. J. Duits, K. Winkel, St. Elisabeth Hospitaal/Stichting Rode Kruis Bloedbank, Willemstad, Curaçao.

Virologists

N. K. T. Back, M. E. G. Bakker, B. Berkhout, S. Jurriaans, H. L. Zaaijer, Academisch Medisch Centrum, Amsterdam; T. Cuijpers, CLB Stichting Sanquin Bloedvoorziening, Amsterdam; P. J. G. M. Rietra, K. J. Roozendaal, Onze Lieve Vrouwe Gasthuis, Amsterdam; W. Pauw, A. P. van Zanten, P. H. M. Smits, Slotervaart Ziekenhuis, Amsterdam; B. M. E. von Blomberg, P. Savelkoul, A. Pettersson, VU Medisch Centrum, Amsterdam; C. M. A. Swanink, Ziekenhuis Rijnstate, Arnhem; P. F. H. Franck, A. S. Lampe, HAGA ziekenhuis, locatie Leyenburg, Den Haag; C. L. Jansen, Medisch Centrum Haaglanden, locatie Westeinde, Den Haag; R. Hendriks, Streeklaboratorium Twente, Enschede; C. A. Benne, J. Schirm Laboratorium voor Infectieziekten, Groningen; D. Veenendaal, Streeklaboratorium Volksgezondheid Kennemerland, Haarlem; H. Storm, J. Weel, J. H. van Zeijl, Laboratorium voor de Volksgezondheid in Friesland, Leeuwarden; A. C. M. Kroes, H. C. J. Claas, Leids Universitair Medisch Centrum, Leiden; C. A. M. V. A. Bruggeman, V. J. Goossens, Academisch Ziekenhuis Maastricht; J. M. D. Galama, W. J. G. Melchers, Y. A. G. Poort, Universitair Medisch Centrum St. Radboud, Nijmegen; G. J. J. Doornum, M. G. Niesters, A. D. M. E. Osterhaus, M. Schutten, Erasmus Medisch Centrum, Rotterdam; A. G. M. Buiting, C. A. M. Swaans, St. Elisabeth Ziekenhuis, Tilburg; C. A. B. Boucher, R. Schuurman, Universitair Medisch Centrum Utrecht; E. Boel, A. F. Jansz, Catharina Ziekenhuis, Veldhoven.

Pharmacologists

A. Veldkamp, Medisch Centrum Alkmaar; J. H. Beijnen, A. D. R. Huitema, Slotervaart Ziekenhuis, Amsterdam; D. M. Burger, P. W. H. Hugen, Universitair Medisch Centrum St. Radboud, Nijmegen; H. J. M. van Kan, Academisch Medisch Centrum (UvA), Amsterdam.

THE MULTICENTER STUDY GROUP ON EUROSIDA

Argentina

M. Losso (site coordinating physician), A. Duran, Hospital J. M. Ramos Mejia, Buenos Aires.

Austria

N. Vetter (site coordinating physician), Pulmologisches Zentrum der Stadt Wien, Vienna.

Belarus

I. Karpov (site coordinating physician), A. Vassilenko, Belarus State Medical University, Minsk, V. M. Mitsura, Gomel State Medical University, Gomel; O. Suetnov, Regional AIDS Centre, Svetlogorsk.

Belgium

N. Clumeck (site coordinating physician), 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 (site coordinating physician), H. Rozsypal, Faculty Hospital Bulovka, Prague; D. Sedlacek, Charles University Hospital, Plzen.

Denmark

J. Nielsen (site coordinating physician), 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 (site coordinating physician), West-Tallinn Central Hospital, Tallinn, Jelena Smidt, Nakkusosakond Sisekliinik, Kohtla-Järve.

Finland

M. Ristola (site coordinating physician), Helsinki University Central Hospital, Helsinki.

France

C. Katlama (site coordinating physician), 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 (site coordinating physician), 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 (site coordinating physician), P. Gargalianos, G. Xylomenos, J. Perdios, Athens General Hospital; G. Panos, A. Filandras, E. Karabatsaki, 1st IKA Hospital; H. Sambattakou, Ippokration Genereal Hospital, Athens.

Hungary

D. Banhegyi (site coordinating physician) Szent Lásló Hospital, Budapest.

Ireland

F. Mulcahy (site coordinating physician), St. James’s Hospital, Dublin.

Israel

I. Yust (site coordinating physician), 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 (site coordinating physician), 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 (site coordinating physician), P. Aldins, Infectology Centre of Latvia, Riga.

Lithuania

S. Chaplinskas (site coordinating physician), Lithuanian AIDS Centre, Vilnius.

Luxembourg

R. Hemmer (site coordinating physician), T. Staub, Centre Hospitalier, Luxembourg.

The Netherlands

P. Reiss (site coordinating physician), Academisch Medisch Centrum bij de Universiteit van Amsterdam, Amsterdam.

Norway

J. Bruun (site coordinating physician), A. Maeland, V. Ormaasen, Ullevål Hospital, Oslo.

Poland

B. Knysz (site coordinating physician), 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 Univesity, Szczecin; M. Beniowski, E. Mularska, Osrodek Diagnostyki i Terapii AIDS, Chorzow; H. Trocha, Medical University, Gdansk.

Portugal

F. Antunes (site coordinating physician), E. Valadas, Hospital Santa Maria, Lisbon; K. Mansinho, Hospital de Egas Moniz, Lisbon; F. Maltez, Hospital Curry Cabral, Lisbon.

Romania

D. Duiculescu (site coordinating physician), Spitalul de Boli Infectioase si Tropicale, Dr. Victor Babes, Bucarest.

Russia

A. Rakhmanova (site coordinating physician), Medical Academy Botkin Hospital, St. Petersburg; E. Vinogradova, St. Petersburg AIDS Centre, St. Peterburg; S. Buzunova, Novgorod Centre for AIDS, Novgorod.

Serbia

D. Jevtovic (site coordinating physician), The Institute for Infectious and Tropical Diseases, Belgrade.

Slovakia

M. Mokrás (site coordinating physician), D. Staneková, Dérer Hospital, Bratislava.

Spain

J. González-Lahoz (site coordinating physician), 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 (site coordinating physician), Karolinska University Hospital, Stockholm; P. O. Persson, Karolinska University Hospital, Huddinge; L. Flamholc, Malmö University Hospital, Malmö.

Switzerland

B. Ledergerber (site coordinating physician), 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 (site coordinating physician) N. Chentsova, Kiev Centre for AIDS, Kiev.

United Kingdom

S. Barton (site coordinating physician) 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, C. Holkmann Olsen, J. Kjær, L. Peters, J. Reekie.

COLLABORATIONS IN HIV OUTCOMES RESEARCH US

Stephen Raffanti, Douglas Dieterch, Amy Justice, Stephen Becker, Anthony Scarsella, Gregory Fusco, Bernard Most, Rukmini Balu, Rashida Rana, Robin Beckerman, Theodore Ising, Jennifer Fusco, Renae Irek, Bernadette Johnson, Ashwin Hirani, Edwin DeJesus, Gerald Pierone, Philip Lackey, Chip Irek, Alison Johnson, John Burdick, Saul Leon, and Joseph Arch.

FRANKFURT HIV COHORT, GERMANY

Schlomo Staszewski, Eilke B. Helm, Amina Carlebach, Axel Müller, Annette Haberl, Gabi Nisius, Tessa Lennemann, Christoph Stephan, Markus Bickel, Manfred Mösch, Peter Gute, Leo Locher, Thomas Lutz, Stephan Klauke, Gabi Knecht, and Pavel Khaykin (Clinical Group); Hans W. Doerr and Martin Stürmer (Virology Group); Errol Babacan (Scientific Advisor and Data Management); Nils von Hentig (Pharmacology Group).

AQUITAINE COHORT, FRANCE

Scientific committee

J. Beylot, G. Chêne, F. Dabis, M. Dupon, M. Longy-Boursier, J. L. Pellegrin, J. M. Ragnaud, and R. Salamon.

Methodological coordination

F. Dabis, G. Chêne, R. Thiébaut, C. Lewden and S. Lawson-Ayayi.

Medical coordination

M. Dupon, P. Mercié, J. F. Moreau, P. Morlat, J. L. Pellegrin, J. M. Ragnaud, N. Bernard, D. Lacoste, D. Malvy, and D. Neau.

Data management and analysis

M. J. Blaizeau, M. Decoin, S. Delveaux, C. Hannapier, S. Labarrère, V. Lavignolle-Aurillac, B. Uwamaliya-Nziyumvira, G. Palmer, D. Touchard, E. Balestre, A. Alioum, H. Jacqmin-Gadda, and R. Thiébaut.

Participating physicians

Bordeaux University Hospital: J. Beylot, P. Morlat, N. Bernard, M. Bonarek, F. Bonnet, B. Coadou, P. Gellie, D. Lacoste, C. Nouts, M. Dupon, F. Bocquentin, H. Dutronc, S. Lafarie, M. Longy-Boursier, P. Mercié, A. Aslan, D. Malvy, T. Pistonne, P. Thibaut, R. Vatan, J. M. Ragnaud, D. Chambon, C. De La Taille, C. Cazorla, D. Neau, A. Ocho, J. L. Pellegrin, J. F. Viallard, O. Caubet, C. Cipriano E. Lazaro, P. Couzigou, L. Castera, H. Fleury, M. E. Lafon, B. Masquelier, I. Pellegrin, D. Breilh, J. F. Moreau, P. Blanco. Dax Hospital: P. Loste, L. Caunègre. Bayonne Hospital: F. Bonnal, S. Farbos, M. Ferrand. Libourne Hospital: J. Ceccaldi, S. Tchamgoué. Mont de Marsan Hospital: S. De Witte. Villeneuve sur Lot Hospital: E. Buy.

BCCFE-HIV

Chris Alexander, Rolando Barrios, Paula Braitstein, Zabrina Brumme, Keith Chan, Helen Cote, Nada Gataric, Josie Geller, Silvia Guillemi, P. Richard Harrigan, Marrianne Harris, Robert Hogg, Ruth Joy, Adrian Levy, Julio Montaner, Val Montessori, Anita Palepu, Elizabeth Phillips, Peter Phillips, Natasha Press, Mark Tyndall, Evan Wood, and Benita Yip.

ROYAL FREE HOSPITAL COHORT

Clinical

S. Bhagani, R. Breen, P. Byrne, A. Carroll, Z. Cuthbertson, A. Dunleavy, A. M. Geretti, B. Heelan, M. Johnson, S. Kinlochde Loes, M. Lipman, S. Madge, N. Marshall, D. Nair, G. Nebbia, B. Prinz, S. Shah, L. Swader, M. Tyrer, M. Youle.

Data management

C. Chaloner, H. Grabowska, J. Holloway, J. Puradiredja, D. Ransom, R. Tsintas.

Biostatistics/epidemiology

W. Bannister, L. Bansi, A. Cozzi-Lepri, Z. Fox, E. Harris, T. Hill, F. Lampe, R. Lodwick, A. Mocroft, A. Phillips, J. Reekie, C. Sabin, C. Smith.

Laboratory

E. Amoah, C. Booth, G. Clewley, A. Garcia Diaz, B. Gregory, G. Janossy, W. Labbett, M. Thomas.

SOUTHERN ALBERTA CLINIC

John Gill, Ron Read, Hartmut Krentz, and Brenda Beckthold.

KÖLN/BONN COHORT

Gerd Faetkenheuer and Norbert Schmeisser.

PISCIS

Coordinators

J. Casabona (CEEISCAT) y JM. Miró (Hospital Clínic-Idibaps, Universitat de Barcelona).

Field coordinator

A. Alquézar (Centre d’Estudis Epidemiològics les infeccions de transmissió sexual i sobre la SIDA de Catalunya [CEEISCAT]).

Steering committee

J. Casabona, A. Esteve, A. Alquézar (CEEISCAT); J. M. Miró (Hospital Clínic-Idibaps, Universitat de Barcelona); D. Podzamczer (Hospital de Bellvitge de Barcelona); J. Murillas (Hospital Son Dureta de Mallorca).

Scientific committee

A. Romero y C. Agustí (CEEISCAT); JM Gatell, F. Agüero (Hospital Clínic-Idibaps, Universitat de Barcelona); C. Tural, B. Clotet (Hospital Universitari Germans Trias i Pujol, Universitat Autónoma de Barcelona); E. Ferrer (Hospital de Bellvitge de Barcelona); M. Riera (Hospital Son Dureta de Mallorca); F. Segura and G. Navarro (Corporació Parc Taulí de Sabadell); L. Force (Hospital de Mataró); J. Vilaró (Hospital de Vic); A. Masabeu (Hospital de Palamós); I. García (Hospital General d’ Hospitalet); M. Guadarrama (Hospital Alt Penedès de Vilafranca).

Data management and statistical analysis

A. Esteve, A. Montoliu y N. Ortega (CEEISCAT), E. Lazzari (Hospital Clínic-Idibaps, Universitat de Barcelona).

Technical support

E. Puchol (CEEISCAT); M. Sanchez (Hospital Clínic-Idibaps, Universitat de Barcelona).

Clinicians involved

J. L. Blanco, F. Garcia-Alcaide, E. Martinez, J. Mallolas, M. López-Dieguez, J. F. García-Goez, (Hospital Clínic-Idibaps, Universitat de Barcelona); G. Sirera, J. Romeu, A. Jou, E. Negredo, C. Miranda, M. C. Capitan (Hospital Universitari Germans Trias i Pujol, Universitat Autónoma de Barcelona); M. Olmo, P. Barragan, M. Saumoy, F. Bolao, C. Cabellos, C. Peña (Hospital Universitari de Bellvitge, L’Hospitalet, Barcelona); M. Sala, M. Cervantes, M. Jose Amengual, M. Navarro, and E. Penelo (Corporació Sanitària Parc Taulí); P. Barrufet (Hospital de Mataró); M. Guadarrama (Hospital Alt Penedès de Vilafranca).

UNIVERSITY OF ALABAMA AT BIRMINGHAM 1917 CLINIC COHORT

Michael S. Saag, principal investigator; James L. Raper, director, administration; Michael J. Mugavero, project director; James H. Willig, informatics; Joseph Schumacher, patient-based metrics; Pei-Wen Chang, database manager; Andrew O. Westfall, Gretchen Cloud, Hui-Yi Lin, statistical analysis; Edward P. Acosta, clinical pharmacologist; Mirjam Colette-Kempf, epidemiology; Jeroan J. Allison, research methodology; Maria Pisu, economics and cost analysis.

UNIVERSITY OF WASHINGTON HIV COHORT

Mari Kitahata.

Footnotes

Presented in part: 14th Conference on Retroviruses and Opportunistic Infections, Los Angeles, California, 25–28 February 2007 (abstract 80).

Potential conflicts of interest. All authors: no conflicts.

Manuscript preparation. The funding sources had no involvement in the design of the study; the collection, analysis, and interpretation of data; the writing of the report; or the decision to submit the article for publication.

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