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Rates of Disease Progression according to Initial Highly Active Antiretroviral Therapy Regimen: A Collaborative Analysis of 12 Prospective Cohort Studies

  1. Antiretroviral Therapy Cohort Collaborationa
  1. Reprints or correspondence: Prof. Matthias Egger, Dept. of Social and Preventive Medicine, University of Bern, Finkenhubelweg 11, Berne CH-3012, Switzerland (egger{at}ispm.unibe.ch)
 
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Abstract

BackgroundNo large clinical end-point trials have been conducted comparing regimens among human immunodeficiency virus type 1–positive persons starting antiretroviral therapy. We examined clinical progression according to initial regimen in the Antiretroviral Therapy Cohort Collaboration, which is based on 12 European and North American cohort studies

MethodsWe analyzed progression to death from any cause and to AIDS or death (AIDS/death), comparing efavirenz (EFV), nevirapine (NVP), nelfinavir, idinavir, ritonavir (RTV), RTV-boosted protease inhibitors (PIs), saquinavir, and abacavir. We also compared nucleoside reverse-transcriptase inhibitor pairs: zidovudine/lamivudine (AZT/3TC), stavudine (D4T)/3TC, D4T/didanosine (DDI), and others

ResultsA total of 17,666 treatment-naive patients, 55,622 person-years at risk, 1617 new AIDS events, and 895 deaths were analyzed. Compared with EFV, the adjusted hazard ratio (HR) for AIDS/death was 1.28 (95% confidence interval [CI], 1.03–1.60) for NVP, 1.31 (95% CI, 1.01–1.71) for RTV, and 1.45 (95% CI, 1.15–1.81) for RTV-boosted PIs. For death, the adjusted HR for NVP was 1.65 (95% CI, 1.16–2.36). The adjusted HR for death for D4T/3TC was 1.35 (95% CI, 1.14–1.59), compared with AZT/3TC

ConclusionsOutcomes may vary across initial regimens. Results are observational and may have been affected by bias due to unmeasured or residual confounding. There is a need for large, randomized, clinical end-point trials

Several clinical trials have compared the effects that nonnucleoside reverse-transcriptase inhibitor (NNRTI)–based and protease inhibitor (PI)–based highly active antiretroviral therapy (HAART) has on biological end points [1–3]. Most recently, the 2NN trial compared efavirenz (EFV)–based and nevirapine (NVP)–based NNRTI regimens and demonstrated that both were valid options for first-line therapy [2]. Other studies have compared the effectiveness of EFV-based and nelfinavir (NFV)–based HAART regimens [4, 5], and the Atlantic and Combine Studies compared NVP-based with idinavir (IDV)- and NFV-based HAART regimens, respectively [3, 6, 7]. However, no trials have compared the clinical efficacy of the most commonly prescribed regimens [8]

In the absence of large-scale trials directly comparing HAART regimens, observational studies might be the only means of identifying potential differences in rates of clinical progression. Several studies have been undertaken [9–13], but none to date has been large enough to examine differences in rates of clinical progression or death. The objective of the present study was to examine whether rates of progression differed according to initial HAART regimen among patients initiating therapy with either a NNRTI- or PI-based regimen

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Methods

ART Cohort Collaboration (ART-CC)The ART-CC is a multinational prospective study of ART-naive HIV-positive patients initiating HAART. The study has been described in detail elsewhere [14–17]. It includes 12 cohort studies from Canada, Europe, and the United States: the French Hospital Database on HIV; the Italian Cohort of Antiretroviral-Naive Patients; the Swiss HIV Cohort Study; the AIDS Therapy Evaluation Project Netherlands; the Multicenter Study Group on EuroSIDA; Collaborations in HIV Outcomes Research–US; the Frankfurt HIV Cohort Study; the Aquitaine Cohort Study; the HAART Observational Medical Evaluation and Research Cohort Study, British Columbia Centre for Excellence in HIV/AIDS; the Royal Free Hospital Cohort Study; the South Alberta Clinic Cohort Study; and the Köln/Bonn Cohort Study. All cohort studies have been approved by institutional review boards, use standardized methods of data collection, and schedule follow-up visits at least once every 6 months. Patient selection and data extraction for the present study were performed at the cohorts’ data centers. Anonymized data on a predefined set of demographic, laboratory, and clinical variables were pooled and analyzed centrally

Statistical analysesAnalyses were restricted to patients who were HIV-1 positive, were ⩾16 years old, had an HIV-1 RNA level ⩾1000 copies/mL at treatment initiation, and first started HAART after 1 January 1996. The primary end points were death from any cause and the combined end point of a new AIDS-defining illness or death (AIDS/death). All centers used the 1993 US Centers for Disease Control and Prevention (CDC) criteria for the definitive or presumptive diagnosis of AIDS-defining opportunistic events [18]. A new AIDS diagnosis was defined as the first occurrence of each AIDS-defining condition; recurrences were not considered. Detectable HIV-1 RNA level (>500 copies/mL) and change in regimen at 6 months after initiation of HAART were secondary outcomes

We measured time from the date of initiation of therapy to the date the end points occurred. For patients free of events, follow-up was censored either on the date of the most recent follow-up visit (for the combined end point) or on the date the patient was last known to be alive (for mortality). Cox regression was used to model the effect that initial treatment regimen and other prognostic factors have on disease progression [19]. All models were stratified by cohort (12 strata) and by calendar year of starting HAART (from 1996 onward, with 2002 and 2003 grouped together; 7 strata). We estimated hazard ratios (HRs) with 95% confidence intervals (CIs), comparing 8 third drugs: EFV, abacavir (ABC), a boosted PI (amprenavir, lopinavir, saquinavir [SQV], or IDV), IDV, NFV, NVP, ritonavir (RTV), and SQV (soft or hard). These models also compared nucleoside reverse-transcriptase inhibitor (NRTI) pairs: zidovudine/lamivudine (AZT/3TC), stavudine (D4T)/3TC, D4T/didanosine (DDI), and others. Patients treated with 4 or more drugs (except when the fourth drug was low-dose RTV used as part of a boosted PI regimen) were excluded from the analyses. We used EFV as the comparator for the third drugs and AZT/3TC as the comparator for the NRTI pairs. Variables considered were age at initiation of HAART (16–29, 30–39, 40–49, and ⩾50 years), sex, transmission risk group (injection drug use [IDU] or non-IDU), CDC clinical stage (A/B or C), CD4 cell count (<25, 25–49, 50–99, 100–199, 200–349, and ⩾350 cells/μL), and plasma HIV-1 RNA level (1000–9999, 10,000–99,999, and ⩾100,000 copies/mL). Variables with Wald P>.2 were omitted from the final models. Analyses followed an “intent to continue initial regimen” principle, in that eligible patients were analyzed according to initial regimen, regardless of whether they later discontinued or modified their therapeutic regimen

We compared the effect that initial regimen had on HIV-1 RNA levels and regimen change at 6 months. Logistic regression models were used to estimate the crude and adjusted odds ratios (ORs) for detectable HIV-1 RNA level (i.e., >500 copies/mL), first for patients with available measurements at 6 months and second for all patients, using the combined-failure end point: detectable HIV-1 RNA level, death, or missing data on HIV-1 RNA level. Logistic models were also used to estimate the crude and adjusted ORs at 6 months for not receiving the initial regimen, first restricted to patients who had clinical follow-up measurements at 6 months (i.e., failure was considered to be either a change of drug regimen or cessation of HAART) and second for all patients (i.e., failure included regimen change, cessation of HAART, death, or missing data). Finally, we assessed whether there was evidence of between-cohort heterogeneity in the effects that initial regimen had on progression to AIDS/death by estimating the effect of initial regimen separately in each cohort and then combining these estimates by use of random-effects meta-analysis. The proportion of the total variance due to heterogeneity between cohorts was estimated using the I2 statistic [20]

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Results

A total of 17,666 patients (55,622 person-years at risk) were available for analyses. A total of 1617 new AIDS events, 895 deaths, and 2017 AIDS cases or deaths were observed over the study period. Table 1 shows prognostic factors by initial drug regimen. The most common third drugs in a combination were IDV (26%), NFV (22%), and EFV and NVP (13%, for both). The most widely used NRTI pair was AZT/3TC (62%), followed by D4T/3TC (20%) and D4T/DDI (10%). The percentage of patients with AIDS ranged from 12% to 34%, and the percentage of patients with a history of IDU ranged from 9% to 26%. At initiation of treatment, the median CD4 cell count was lower in patients receiving RTV-boosted PIs than in patients receiving other regimens (130 vs. 240 cells/μL). The number and percentage of patients receiving each drug by cohort and by calendar year is shown in tables 2 and 3

Table 1
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Table 1

Baseline prognostic factors for study patients, by third drug and nucleoside reverse-transcriptase inhibitor (NRTI) pair

Table 2
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Table 2

Receipt of each drug, by cohort

Table 3
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Table 3

Receipt of each drug, by year of starting highly active antiretroviral therapy

Table 4 shows crude and adjusted HRs for AIDS/death and for death, for both third drugs and for NRTI pairs. When AIDS/death was considered, the adjusted HRs were 1.28 (95% CI, 1.03–1.60) for NVP, 1.31 (95% CI, 1.01–1.71) for RTV, and 1.45 (95% CI, 1.15–1.81) for boosted regimens. There was little difference in the effect of the NRTI pairs. When mortality was considered, patients receiving EFV appeared to do best, but there was little evidence that the HR for death differed according to other third drugs, except for NVP: the adjusted HR relative to EFV was 1.65 (95% CI, 1.16–2.36). Compared with patients receiving AZT/3TC, the adjusted HR for death for patients receiving D4T/3TC was 1.35 (95% CI, 1.14–1.59). Again, there was little evidence of differences in rates according to other NRTI pairs. We found little evidence of between-cohort heterogeneity in the effect that the drugs had on clinical outcomes, except for RTV-boosted PIs (I2=47%) and D4T/3TC (I2=56%). The heterogeneity of the effect that RTV-boosted PIs had among cohorts might have been due to different PIs being prescribed

Table 4
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Table 4

Crude and adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for the end point of death from any cause and for the combined end point of AIDS or death (AIDS/death)

Table 5 shows crude and adjusted ORs for detectable HIV-1 RNA level at 6 months after initiation of HAART for each third drug and NRTI pair. Patients who started with EFV-containing regimens were more likely than patients who started with any other third drug to suppress HIV-1 RNA level by the 6-month time point: adjusted ORs for the comparison with EFV ranged from 1.67 (95% CI, 1.35–2.07) for boosted PIs to 5.33 (95% CI, 4.25–6.69) for SQV. These patterns were also seen when patients with missing data or who had died were considered to have experienced virological failure, although ORs were generally attenuated. Patients receiving other NRTI pairs were at greater risk of having a detectable HIV-1 RNA level at 6 months, compared with patients receiving AZT/3TC. Table 6 shows the crude and adjusted ORs for regimen change at 6 months after initiation of HAART for each third drug and NRTI pair. The drug most likely to result in regimen change was RTV (adjusted OR, 4.53 [95% CI, 3.69–5.57]). ORs were slightly attenuated when those patients with missing data or who had died were considered to have experienced treatment failure

Table 5
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Table 5

Crude and adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for detectable HIV-1 RNA level at 6 months after initiation of highly active antiretroviral therapy (HAART), for patients with a 6-month HIV-1 RNA measurement (end point considered as detectable HIV-1 RNA level at 6 months) and for all patients (end point considered as detectable HIV-1 RNA level at 6 months, missing, or dead)

Table 6
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Table 6

Crude and adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for regimen change at 6 months, for patients with 6 months of follow-up (end point considered as regimen change at 6 months) and for all patients (end point considered as regimen change at 6 months, missing, or dead)

In sensitivity analyses, we examined whether the NRTI pair modifies the effect of NFV (compared with that of EFV) by including an interaction term in the model. There was no evidence of interaction between EFV or NFV and the NRTI pairs for AIDS/death (P=.36) or for death (P=.78). However, there was evidence of interaction for the outcome of detectable HIV-1 RNA level at 6 months (P=.02) and of regimen change at 6 months (P=.04). For suppression of HIV-1 RNA level, EFV was more effective with AZT/3TC than with D4T/DDI, but there was no evidence of a difference in efficacy between the NRTI pairs when combined with NFV. In light of the results for regimen change, it appears that the combination of EFV with D4T/DDI was less likely to be maintained than was AZT/3TC, whereas NFV was most frequently maintained with D4T/DDI as the NRTI pair

We examined whether the adjusted HR for NVP (compared with EFV) for all-cause mortality remained elevated if we restricted follow-up to 6 months, when patients were most likely to be still receiving their initial regimen. Compared with EFV, the adjusted HR for all-cause mortality for NVP was 2.28 (95% CI, 1.20–4.36) during the first 6 months, which decreased to 1.31 (95% CI, 0.81–2.18) after 6 months. We examined the hypothesis that, because of selective differences in toxicities, patients who initiated therapy at a high CD4 cell count would be at a greater risk of death if they were receiving NVP-based HAART than would those receiving other regimens. We believed that this difference would be especially pronounced in women and those who were positive for hepatitis C virus (HCV). Table 7 shows HRs for death, comparing NVP with all other third drugs in models including interaction terms for sex, high CD4 cell count (⩾350 cells/μL), and IDU, first for all patients and second restricted to patients with known HCV status. The data are consistent with the hypothesis that the risk of death is increased in women with high CD4 cell counts, especially those who are HCV positive. However, the power to detect interaction effects was low

Table 7
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Table 7

Adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for the end point of death from any cause, comparing nevirapine with other third drugs in models including interactions with sex, CD4 cell count, injection drug use (IDU), and hepatitis C virus (HCV) infection status

We evaluated patterns of survival after 6 months of therapy, accounting for the initial response to HAART. The adjusted model controlled for CDC clinical stage, CD4 cell count, and HIV-1 RNA level at 6 months as well as age, IDU status, and clinical stage at initiation of HAART. At 6 months, compared with EFV, elevated crude HRs for mortality were observed for RTV (1.73 [95% CI, 1.02–2.91]) and for RTV-boosted PI regimens (1.76 [95% CI, 1.02–3.01]). However, these HRs were attenuated in the multivariable analysis, to 1.09 (95% CI, 0.64–1.87) for RTV and to 1.00 (95% CI, 0.58–1.73) for boosted regimens, suggesting that the higher HRs resulted from poor immunological and virological response during the first 6 months. The corresponding crude HR for NVP was 1.57 (95% CI, 0.97–2.54), which was attenuated to 1.33 (95% CI, 0.81–2.18). Therefore, the excess deaths in those who started with NVP, compared with deaths in those who started with EFV, might not have been the result of poor initial response. Among those who subsequently died, the mean CD4 cell count measured at 6 months was 403 cells/μL for those who started with NVP, compared with 294 cells/μL for those who started with other drugs, showing that the deaths of those who started with NVP occurred in less immunologically suppressed individuals

We examined whether the effects of drug regimens differed according to whether patients’ presumed transmission was via IDU. Models including and excluding the interaction between each third drug and IDU status were compared using likelihood ratio tests. In analyses that used separate models for IDU and non-IDU, the HRs for the third drugs were generally attenuated for non-IDU and increased for IDU. There was evidence only of an interaction between the third drug and IDU for NVP (P=.05). Results from analyses restricted to patients with a history of IDU, patients without a history of IDU, patients with a baseline CD4 cell count >200 cells/μL, and patients who started HAART after 1 January 1998 and for all patients but with follow-up censored at 2 years after starting HAART are presented in table 8. Censoring at 2 years did not affect estimates substantially. The HR for NVP was increased to 1.43 (95% CI, 0.97–2.10) in patients with a CD4 cell count >200 cells/μL at initiation of HAART. When the analysis was restricted to those starting HAART after 1 January 1998, the HR for RTV was increased to 1.41 (95% CI, 0.96–2.08)

Table 8
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Table 8

Crude and adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for the end point of death from any cause and for the combined end point of AIDS or death (AIDS/death), from sensitivity analyses for all patients but with follow-up censored at 2 years after starting highly active antiretroviral therapy (HAART) and restricted to patients without a history of injection drug use (IDU), patients with a history of IDU, patients starting HAART after 1 January 1998, and patients with a CD4 cell count >200 cells/μL at initiation of HAART

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Discussion

Thanks to a collaborative effort involving 12 different studies, the prognosis of HIV infection in patients initiating HAART could be elucidated for several initial regimens. We found that the choice of drugs used in the initial regimen was associated with the probability of viral suppression and with the sustained use of this regimen 6 months after starting HAART. We observed few differences in the rates of mortality between regimens, and these rates were much lower than were those in the pre-HAART era [21]. EFV performed the best of the third drugs, but several other drugs had similar effectiveness. Compared with EFV, the highest mortality risk was for patients who initiated HAART by receiving NVP

In the absence of large trials, the present observational study provides important information on potential differences between regimens. Because all patients involved were treatment naive, our results were not confounded by previous ART and are relevant to many patients starting HAART. Data were combined across continents and countries, and our results should, therefore, be generalizable. Confounding is an important issue, because prognostic factors differed between groups of patients starting different regimens. Additional, unmeasured confounding factors could have distorted our results. Cox models were stratified both by cohort and by calendar year, and the results should not, therefore, be biased by between-cohort differences in treatment choices or by secular changes in the risk of the end points. AIDS diagnoses were not centrally reviewed or verified, which may have introduced bias due to misclassification. However, all cohorts used the same CDC criteria for the prospective diagnosis of AIDS-defining events, and study clinics are based in specialized centers with extensive expertise in HIV medicine. Some patients may have participated in clinical trials comparing different initial regimens, but it is likely that the proportion of such patients was small, and enrollment in the cohorts was independent of participation in trials

HRs changed after adjustments were made for prognostic factors in multivariable models. In all cases except for NVP-based regimens, effects were attenuated. For example, in the unadjusted analysis, PI regimens boosted with RTV were associated with a 2-fold higher rate of AIDS/death (HR, 2.07), but this effect was considerably smaller after adjustments were made for prognostic factors (HR, 1.45), because these combinations were more likely to be prescribed to patients with more-advanced disease. Prognostic factors will have been subject to measurement error, and, therefore, it is possible that, because of residual confounding, the adjusted HR continues to be an overestimate of the true risk associated with boosted PI regimens. The opposite was the case for NVP-based therapies: patients at lower risk of progression were more likely to have received these regimens, and adjustment for prognostic factors at baseline, therefore, increased the HR for progression to AIDS/death, from 1.04 to 1.28. It is, therefore, possible that, because of residual confounding, the adjusted HR underestimates the true increase in the risk of progression associated with NVP

Differences in outcome between EFV and NVP might have been the result of confounding by indication if patients with a poorer propensity to adhere tended to be prescribed NVP in preference to EFV. To distinguish this possibility from differences in discontinuation rates due to differences in efficacy or toxicity would require data both on reasons for choice of drug regimen and on reasons for discontinuation, which are difficult to collect. It is also important to consider whether observed differences could have been the result of differences in socioeconomic status [22, 23]. However, except for the United States, our patient populations came from countries where all individuals (with the possible exception of migrants of sub-Saharan African origin, who are not always legal migrants) had similar low-cost access to HAART and laboratory monitoring

Our analyses did not account for adherence to treatment, because this information was not available. Formally, adherence to treatment cannot confound the effect of initial regimen, because it occurs subsequent to the choice of regimen. Rather, failure to adhere to treatment is likely to modify the effect of treatment, because poor adherence has been shown in previous studies to be associated with poor CD4 cell count and HIV-1 RNA response as well as mortality [24–27]. However, choice of initial regimen might be affected by physicians’ perception of the extent to which the patient is likely to adhere to treatment [25, 28, 29], because different HAART regimens have clear differences in pill burden [28, 30]. This is reflected, for example, in the fact that presumed mode of transmission is associated with initial regimen. Unmeasured patient characteristics that affect propensity to adhere and also predict choice of regimen could confound our results

Although our analyses were conducted on the basis of intent to continue initial regimen, 27% of patients were no longer receiving their initial regimen at 6 months after initiation. Those patients initially receiving RTV (46%) or RTV-boosted PIs (40%) were particularly likely to change regimens. To estimate the effect of initial regimen accounting for regimen change would be difficult, since regimen-specific factors (such as toxicities) will themselves be associated with regimen change

Large variations in therapeutic responses by initial regimen have been observed previously. A recent meta-analysis of clinical trials comparing HAART regimens among persons with extensive ART experience demonstrated that unboosted PI regimens were clearly superior to NNRTI regimens based on NVP or delavirdine [31]. In particular, CD4 cell count response and the suppression of viral replication was found to be less for NNRTI regimens than for PI regimens. In contrast, a systematic review of trials evaluating HAART regimens in treatment-naive HIV-infected adults demonstrated that boosted PI and NNRTI regimens provided superior virological suppression than did PI and triple nucleoside-containing regimens [32]. However, boosted PI regimens showed the greatest increase in CD4 cell counts, compared with the other 3 regimen types

Our results do not confirm the main findings from the 2NN trial [2], although a sensitivity analysis in the 2NN trial, which included only those participants who received at least 1 dose of drugs, did find a significant benefit of EFV [2, 33, 34]. In our analysis, EFV appears to be more efficacious than any other third drug in a HAART regimen. These differences could be attributed to the superiority of EFV or might reflect underlying unmeasured differences in the ways in which physicians prescribe and patients use EFV, compared with other third drugs [28, 35–37]. Other observational studies have also suggested that EFV may be more efficacious than NVP with regard to CD4 cell count gain and virological efficacy [38, 39]. Of note, in our study, differences in viral load response were not generally associated with differences in rates of mortality, and differences in rates of mortality between EFV and NVP were associated with deaths that occurred during the first 6 months. These deaths could have been the result of either drug-induced toxicities or other factors not related to toxicity or therapeutic response [40]. The 2NN trial lacked the power to demonstrate, or to exclude with certainty, smaller differences in rates of mortality

The present study arose from the need to characterize differences in response and survival by initial HAART regimen. No previous observational study has examined this issue with such a large patient population or large number of regimen types. Some of the third drugs analyzed here are no longer being prescribed in most settings, and there is a need for future work to examine regimens that have been prescribed in more recent years, once sufficient numbers of patients and follow-up time have accrued. The long-term impact of initial regimen choice may not be evident after 3 years of follow-up. It is not possible to simultaneously compare recently prescribed drug regimens and long-term effects—our approach represents a compromise between these 2 competing requirements

In conclusion, the choice of drugs used in the initial HAART regimen is associated with the probability of viral suppression and with the sustained use of this regimen 6 months after the start of HAART. However, poorer response and higher rate of regimen change do not necessarily indicate subsequent differences in mortality. We cannot rule out confounding, rather than differences in drug effectiveness, as an explanation for our findings. Large clinical trials that are powered to assess differences in clinical outcomes are required to produce a more-definitive answer, and we strongly urge funding bodies to support such large, long-term trials in the future

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ART-CC Analysis and Writing Committee Members

Robert Hogg (Division of Epidemiology and Population Health, British Columbia Centre for Excellence in HIV/AIDS, Vancouver, Canada), Margaret May (Department of Social Medicine, University of Bristol, Bristol, United Kingdom), Andrew N. Phillips (Department of Primary Care and Population Sciences, Royal Free and University College Medical School, London, United Kingdom), Dominique Costagliola (INSERM, UMR S 720; Université Pierre et Marie Curie–Paris 6, UMR S 720, Paris, France), Jonathan A. C. Sterne (Department of Social Medicine, University of Bristol, Bristol, United Kingdom), Caroline A. Sabin (Department of Primary Care and Population Sciences, Royal Free and University College Medical School, London, United Kingdom), Frank De Wolf (HIV Monitoring Foundation, Amsterdam, The Netherlands, and Department of Infectious Disease Epidemiology, Imperial College, Faculty of Medicine, London, United Kingdom), Bruno Ledergerber (Division of Infectious Diseases and Hospital Epidemiology, University of Zurich, Zurich, Switzerland), Antonella D’Arminio Monforte (Clinic of Infectious Diseases and Tropical Medicine, “San Paolo” Hospital, University of Milan, Italy), Amy Justice (Yale University School of Medicine, New Haven, and VA Connecticut Healthcare System, West Haven, Connecticut), John Gill (Division of Infectious Diseases, University of Calgary, Calgary, Canada), Gregory Fusco (Department of International Clinical Virology, GlaxoSmithKline, Research Triangle Park, North Carolina), Schlomo Staszewski (HIVCENTER, Hospital of the J. W. Goethe University, Frankfurt, Germany), Jürgen Rockstroh (Department of Medicine I, University of Bonn, Germany), Geneviève Chêne (INSERM, U593; Université Victor Segalen Bordeaux 2; CHU Bordeaux, France), and Matthias Egger (Department of Social and Preventive Medicine, University of Bern, Bern, Switzerland)

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Acknowledgments

We are grateful to all patients, doctors, and study nurses who were involved in the participating cohort studies

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Footnotes

  • ↵(See the editorial commentary by Hughes, on pages 542–4.)

  • ↵Presented in part: 3rd IAS Conference on HIV Pathogenesis and Treatment, Rio de Janeiro, 24–27 July 2005 (abstract MoDe0301)

    Potential conflicts of interest: A.N.P. has received travel grants, grants, consultancy fees, and honoraria from various pharmaceutical companies, including Roche, DuPont, Bristol-Myers Squibb (BMS), Boehringer Ingelheim (BI), and GlaxoSmithKline (GSK). M.E. has received travel grants, grants, or honoraria from BMS, BI, and GSK. B.L. has received travel grants from Roche, Abbott, BMS, GSK, Merck Sharp and Dohme, and Aventis. C.A.S. has received honoraria, consultancy fees, and travel grants from a number of pharmaceutical companies, including Roche, BMS, BI, Gilead Sciences, and GSK. M.M. and J.A.C.S. have received travel grants from GSK. G.F. is an employee of GSK. D.C. has received travel grants, consultancy fees, and honoraria from various pharmaceutical companies, including Abbott, GSK, BMS, Gilead, Roche, and BI

    Financial support: UK Medical Research Council (grant RD1564 to the Antiretroviral Therapy Cohort Collaboration). 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; Stichting HIV Monitoring; the European Commission; the governments of British Columbia and Alberta; the Michael Smith Foundation for Health Research; the Canadian Institutes of Health Research; and GlaxoSmithKline, Roche, and Boehringer Ingelheim (unrestricted grants)

  • ↵Analysis and writing committee members are listed at the end of the text, and a complete list of study group members is given in the Appendix, which is not available in the print edition of the Journal

  • Received November 28, 2005.
  • Accepted February 27, 2006.
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Appendix The Antiretroviral Therapy Cohort Collaboration

Analysis and writing committeeRobert Hogg, Margaret May, Andrew N. Phillips, Dominique Costagliola, Jonathan A. C. Sterne, Caroline A. Sabin, Frank De Wolf, Bruno Ledergerber, Antonella D’Arminio Monforte, Amy Justice, John Gill, Gregory Fusco, Schlomo Staszewski, Jürgen Rockstroh, Geneviève Chêne, and Matthias Egger

Steering committeeDominique Costagliola, François Dabis, Antonella D’Arminio Monforte, Frank de Wolf, Matthias Egger, Gerd Fatkenheuer, John Gill, Robert Hogg, Amy Justice, Bruno Ledergerber, Jens Lundgren, Margaret May, Andrew N. Phillips, Peter Reiss, Caroline A. Sabin, Schlomo Staszewski, Jonathan A. C. Sterne, and Ian Weller

Data managersMargaret May, Brenda Beckthold, Benita Yip, Brenda Dauer, Jenifer Fusco, Sophie Grabar, Cornelia Junghans, Valerie Lavignolle, Ard van Sighem, Edwige Pereira, Patrizio Pezzotti, Andrew N. Phillips, Caroline A. Sabin, and Nobert Schmeisser

The members of the 12 study groups are as follows:

French Hospital Database on HIV (61 sites)Scientific committee: E. Billaud, F. Boué, D. Costagliola, X. Duval, C. Duvivier, P. Enel, S. Fournier, J. Gasnault, C. Gaud, J. Gilquin, S. Grabar, M. A. Khuong, J. M. Lang, M. Mary-Krause, S. Matheron, M. C. Meyohas, G. Pialoux, I. Poizot-Martin, C. Pradier, E. Rouveix, D. Salmon-Ceron, A. Sobel, P. Tattevin, H. Tissot-Dupont, and Y. Yasdanpanah. DMI2 coordinating center: French Ministry of Health (E. Aronica, V. Tirard-Fleury, and I. Tortay). Statistical analysis center: INSERM EMI 0214 (S. Abgrall, D. Costagliola, S. Grabar, M. Guiguet, E. Lanoy, H. Leneman, L. Lièvre, M. Mary-Krause, V. Potard, and S. Saidi). CISIH, Paris area: CISIH de Bichat–Claude Bernard (Hôpital Bichat–Claude Bernard: S. Matheron, J. L. Vildé, C. Leport, P. Yeni, E. Bouvet, C. Gaudebout, B. Crickx, and C. Picard-Dahan), CISIH de Paris–Centre Ouest (Hôpital Européen Georges Pompidou: L. Weiss and D. Tisne-Dessus; G. H. Tarnier-Cochin: D. Sicard and D. Salmon; Hôpital Saint-Joseph: J. Gilquin and I. Auperin; Hôpital Necker adultes: J. P. Viard and L. Roudière), CISIH de Paris–Sud (Hôpital Antoine Béclère: F. Boué and R. Fior; Hôpital de Bicêtre: J. F. Delfraissy and C. Goujard; Hôpital Henri Mondor: Ph. Lesprit and C. Jung; Hôpital Paul Brousse), CISIH de Paris–Est (Hôpital Saint-Antoine: M. C. Meyohas, J. L. Meynard, O. Picard, and N. Desplanque; Hôpital Tenon: J. Cadranel, C. Mayaud, G. Pialoux, and W. Rozenbaum), CISIH de Pitié-Salpétrière (GH Pitié–Salpétrière: F. Bricaire, C. Katlama, S. Herson, and A. Simon), CISIH de Saint-Louis (Hôpital Saint-Louis: J. M. Decazes, J. M. Molina, J. P. Clauvel, and L. Gerard; GH Lariboisière–Fernand Widal: P. Sellier and M. Diemer), CISIH 92 (Hôpital Ambroise Paré: C. Dupont, H. Berthé, and P. Saïag; Hôpital Louis Mourier: E. Mortier and C. Chandemerle; Hôpital Raymond Poincaré: P. de Truchis), CISIH 93 (Hôpital Avicenne: M. Bentata and P. Honoré; Hôpital Jean Verdier: S. Tassi and V. Jeantils; Hôpital Delafontaine: D. Mechali and B Taverne). CISIH, outside Paris area: CISIH Auvergne-Loire (CHU de Clermont-Ferrand: H. Laurichesse and F. Gourdon; CHRU de Saint-Etienne: F. Lucht and A. Fresard); CISIH de Bourgogne–Franche Comté (CHRU de Besançon; CHRU de Dijon; CH de Belfort: J. P. Faller and P. Eglinger; CHRU de Reims); CISIH de Caen (CHRU de Caen: C. Bazin and R. Verdon), CISIH de Grenoble (CHU de Grenoble), CISIH de Lyon (Hôpital de la Croix-Rousse: D. Peyramond and A. Boibieux; Hôpital Edouard Herriot: J. L. Touraine and J. M. Livrozet; Hôtel-Dieu: C. Trepo and L. Cotte), CISIH de Marseille (Hôpital de la Conception: I. Ravaux and H. Tissot-Dupont; Hôpital Houphouët-Boigny: J. P. Delmont and J. Moreau; Institut Paoli Calmettes: J. A. Gastaut; Hôpital Sainte-Marguerite: I. Poizot-Martin, J. Soubeyrand, and F. Retornaz; CHG d’Aix-En-Provence: P. A. Blanc and T. Allegre; Centre pénitentiaire des Baumettes: A. Galinier and J. M. Ruiz; CH d’Arles; CH d’Avignon: G. Lepeu; CH de Digne Les Bains: P. Granet-Brunello; CH de Gap: L. Pelissier and J. P. Esterni; CH de Martigues: M. Nezri and R. Cohen-Valensi; CHI de Toulon: A. Laffeuillade and S. Chadapaud), CISIH de Montpellier (CHU de Montpellier: J. Reynes; CHG de Nîmes), CISIH de Nancy (Hôpital de Brabois: T. May and C. Rabaud), CISIH de Nantes (CHRU de Nantes: F. Raffi and E. Billaud), CISIH de Nice (Hôpital Archet 1: C. Pradier and P. Pugliese; CHG Antibes Juan les Pins), CISIH de Rennes (CHU de Rennes: C. Michelet and C. Arvieux), CISIH de Rouen (CHRU de Rouen: F. Caron and F. Borsa-Lebas), CISIH de Strasbourg (CHRU de Strasbourg: J. M. Lang, D. Rey, and P. Fraisse; CH de Mulhouse), CISIH de Toulouse (CHU Purpan: P. Massip, L. Cuzin, E. Arlet-Suau, and 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). CISIH, overseas: CISIH de Guadeloupe (CHRU de Pointe-à-Pitre), CISIH de Guyane (CHG de Cayenne: M. Sobesky and R. Pradinaud), CISIH de Martinique (CHRU de Fort-de-France), CISIH de La Réunion (CHD Félix Guyon: C. Gaud and M. Contant)

Italian Cohort of Antiretroviral-Naive Patients (47 sites)Ancona: M. Montroni, G. Scalise, M. C. Braschi, and A. Riva. Aviano (PN): U. Tirelli and R. Cinelli. Bari: G. Pastore, N. Ladisa, and G. Minafra. Bergamo: F. Suter and C. Arici. Bologna: F. Chiodo, V. Colangeli, C. Fiorini, and O. Coronado. Brescia: G. Carosi, G. P. Cadeo, C. Torti, C. Minardi, and D. Bertelli. Busto Arsizio: G. Rizzardini and S. Melzi. Cagliari: P. E. Manconi and P. Piano. Catanzaro: L. Cosco and A. Scerbo. Chieti: J. Vecchiet and M. D’Alessandro. Como: D. Santoro and L. Pusterla. Cremona: G. Carnevale and P. Citterio. Cuggiono: P. Viganò and M. Mena. Ferrara: F. Ghinelli and L. Sighinolfi. Firenze: F. Leoncini, F. Mazzotta, M. Pozzi, and S. Lo Caputo. Foggia: G. Angarano, B. Grisorio, A. Saracino, and S. Ferrara. Galatina (LE): P. Grima and P. Tundo. Genova: G. Pagano, G. Cassola, A. Alessandrini, and R. Piscopo. Grosseto: M. Toti and S. Chigiotti. Latina: F. Soscia and L. Tacconi. Lecco: A. Orani and P. Perini. Lucca: A. Scasso and A. Vincenti. Macerata: F. Chiodera and P. Castelli. Mantova: A. Scalzini and L. Palvarini. Milano: M. Moroni, A. Lazzarin, A. Cargnel, G. M. Vigevani, L. Caggese, A. d’Arminio Monforte, D. Repetto, A. Galli, S. Merli, C. Pastecchia, and M. C. Moioli. Modena: R. Esposito and C. Mussini. Napoli: N. Abrescia, A. Chirianni, C. M. Izzo, M. Piazza, M. De Marco, R. Viglietti, E. Manzillo, and S. Nappa. Palermo: A. Colomba, V. Abbadessa, T. Prestileo, and S. Mancuso. Parma: C. Ferrari and P. Pizzaferri. Pavia: G. Filice, L. Minoli, R. Bruno, and S. Novati. Perugia: F. Baldelli and M. Tinca. Pesaro: E. Petrelli and A. Cioppi. Piacenza: F. Alberici and A. Ruggieri. Pisa: F. Menichetti and C. Martinelli. Potenza: C. De Stefano and A. La Gala. Ravenna: G. Ballardini and E. Rizzo. Reggio Emilia: G. Magnani and M. A. Ursitti. Rimini: M. Arlotti and P. Ortolani. Roma: R. Cauda, F. Dianzani, G. Ippolito, A. Antinori, G. Antonucci, S. D’Elia, P. Narciso, N. Petrosillo, V. Vullo, A. De Luca, A. Bacarelli, M. Zaccarelli, R. Acinapura, P. De Longis, A. Brandi, M. P. Trotta, P. Noto, M. Lichtner, M. R. Capobianchi, F. Carletti, E. Girardi, P. Pezzotti, and G. Rezza. Sassari: M. S. Mura and M. Mannazzu. Torino: P. Caramello, G. Di Perri, M. L. Soranzo, G. C. Orofino, I. Arnaudo, and M. Bonasso. Varese: P. A. Grossi and C. Basilico. Verbania: A. Poggio and G. Bottari. Venezia: E. Raise and F. Ebo. Vicenza: F. De Lalla and G. Tositti. Taranto: F. Resta and K. Loso. London, UK: A. Cozzi Lepri

Swiss HIV Cohort Study (7 sites)M. Battegay, E. Bernasconi, J. Böni, H. Bucher, Ph. Bürgisser, S. Cattacin, M. Cavassini, R. Dubs, M. Egger, L. Elzi, P. Erb, K. Fantelli, M. Fischer, M. Flepp, A. Fontana, P. Francioli (president of the Swiss HIV Cohort Study, Centre Hospitalier Universitaire Vaudois), H. Furrer (chairman of the clinical and laboratory committee), M. Gorgievski, H. Günthard, B. Hirschel, L. Kaiser, C. Kind, Th. Klimkait, U. Lauper, B. Ledergerber, M. Opravil, F. Paccaud, G. Pantaleo, L. Perrin, J.-C. Piffaretti, M. Rickenbach (head of the data center), C. Rudin (chairman of the Mother and Child Substudy), P. Schmid, J. Schüpbach, R. Speck, A. Telenti, A. Trkola, P. Vernazza (chairman of the scientific board), R. Weber, and S. Yerly

AIDS Therapy Evaluation Project Netherlands (25 sites)Treating physicians (asterisks indicate site coordinating physicians): W. Bronsveld* and M. E. Hillebrand-Haverkort (Alkmaar); J. M. Prins,* J. C. Bos, J. K. M. Eeftinck Schattenkerk, S. E. Geerlings, M. H. Godfried, J. M. A. Lange, F. C. van Leth, S. H. Lowe, J. T. M. van der Meer, F. J. B. Nellen, K. Pogány, T. van der Poll, P. Reiss, Th. A. Ruys, S. Sankatsing, R. Steingrover, G. van Twillert, M. van der Valk, M. G. A. van Vonderen, S. M. E. Vrouenraets, M. van Vugt, and F. W. M. N. Wit (Amsterdam); T. W. Kuijpers, D. Pajkrt, and H. J. Scherpbier, Emmakinderziekenhuis (Amsterdam); A. van Eeden,* Onze Lieve Vrouwe Gasthuis (Amsterdam); J. H. ten Veen,* P. S. van Dam, and J. C. Roos, Onze Lieve Vrouwe Gasthuis (Amsterdam); K. Brinkman,* P. H. J. Frissen, and H. M. Weigel, Onze Lieve Vrouwe Gasthuis (Amsterdam); J. W. Mulder,* E. C. M. van Gorp, P. L. Meenhorst, and A. T. A. Mairuhu, Slotervaart Ziekenhuis (Amsterdam); J. Veenstra* (Amsterdam); S. A. Danner,* M. A. Van Agtmael, F. A. P. Claessen, R. M. Perenboom, A. Rijkeboer, and M. van Vonderen (Amsterdam); C. Richter,* J. van der Berg, and R. van Leusen (Arnhem); R. Vriesendorp* and F. J. F. Jeurissen (Westeinde-Den Haag); R. H. Kauffmann* and E. L. W. Koger (Leyenburg-Den Haag); B. Bravenboer* and Catharina Ziekenhuis-Eindhoven; C. H. H. ten Napel* and G. J. Kootstra, Medisch Spectrum Twente-Enschede; H. G. Sprenger,* W. M. A. J. Miesen, R. Doedens, and E. H. Scholvinck (Groningen); R. W. ten Kate,* Kennemer Gasthuis-Haarlem; D. P. F. van Houte* and M. Polee (Zuid); F. P. Kroon,* P. J. van den Broek, J. T. van Dissel, and E. F. Schippers (Leiden); G. Schreij,* S. van de Geest, and A. Verbon (Maastricht); P. P. Koopmans,* M. Keuter, F. Post, and A. J. A. M. van der Ven (Nijmegen); M. E. van der Ende,* I. C. Gyssens, M. van der Feltz, J. G. den Hollander, S. de Marie, J. L. Nouwen, B. J. A. Rijnders, and T. E. M. S. de Vries (Rotterdam); G. Driessen, R. de Groot, and N. Hartwig (Rotterdam); J. R. Juttmann,* C. van de Heul, and M. E. E. van Kasteren, St. Elisabeth (Tilburg); M. M. E. Schneider* (until October 2004), M. J. M. Bonten, J. C. C. Borleffs, P. M. Ellerbroek, I. M. Hoepelman,* C. A. J. J. Jaspers, I. Schouten, and C. A. M. Schurink (Utrecht); S. P. M. Geelen and T. F. W. Wolfs (Utrecht); W. L. Blok* and A. A. Tanis (Vlissingen); P. H. P. Groeneveld* and Isala Klinieken-Zwolle. Virologists: N. K. T. Back, M. E. G. Bakker, B. Berkhout, and S. Jurriaans (Amsterdam); Th. Cuijpers (Amsterdam); P. J. G. M. Rietra and K. J. Roozendaal (Amsterdam); W. Pauw, A. P. van Zanten, and P. H. M. Smits (Amsterdam); B. M. E. von Blomberg and P. Savelkoul (Amsterdam); C. M. A. Swanink (Arnhem); P. F. H. Franck and A. S. Lampe, HAGA (Leyenburg-Den Haag); C. L. Jansen (Westeinde-Den Haag); R. Hendriks, Streeklaboratorium Twente–Enschede; J. Schirm and C. A. Benne (Groningen); D. Veenendaal (Haarlem); H. Storm, J. Weel, and J. H. van Zeijl (Leeuwarden); A. C. M. Kroes and H. C. J. Claas (Leiden); C. A. M. V. A. Bruggeman and V. J. Goossens (Maastricht); J. M. D. Galama, W. J. G. Melchers, and Y. A. G. Poort (Nijmegen); G. J. J. Doornum, M. G. Niesters, A. D. M. E. Osterhaus, and M. Schutten (Rotterdam); A. G. M. Buiting and C. A. M. Swaans (Tilburg); C. A. B. Boucher and R. Schuurman (Utrecht); E. Boel and A. F. Jansz (Veldhoven)

Multicenter Study Group on EuroSIDA (73 sites)Argentina (asterisks indicate national coordinators): M. Losso* and A. Duran (Buenos Aires). Austria: N. Vetter* (Vienna). Belarus: I. Karpov* and A. Vassilenko (Minsk). Belgium: N. Clumeck,* S. De Wit, and B. Poll (Brussels); R. Colebunders (Antwerp). Czech Republic: L. Machala and *H. Rozsypal (Prague); D. Sedlacek (Plzen). Denmark: J. Nielsen,* J. Lundgren, T. Benfield, and O. Kirk (Copenhagen); J. Gerstoft, T. Katzenstein, A.-B. E. Hansen, and P. Skinhøj (Copenhagen); C. Pedersen (Odense). Estonia: K. Zilmer* (Tallinn). France: C. Katlama,* J.-P. Viard, and P.-M. Girard (Paris); T. Saint-Marc and P. Vanhems (Lyon); C. Pradier (Nice); F. Dabis (Bordeaux). Germany: M. Dietrich and C. Manegold (Hamburg); J. van Lunzen and H.-J. Stellbrink (Hamburg); S. Staszewski and M. Bickel (Frankfurt); F.-D. Goebel (Munich); G. Fätkenheuer (Cologne); J. Rockstroh (Bonn); R. Schmidt (Hannover). Greece: J. Kosmidis,* P. Gargalianos, H. Sambatakou, J. Perdios, G. Panos, A. Filandras, and E. Karabatsaki (Athens). Hungary: D. Banhegyi* (Budapest). Ireland: F. Mulcahy* (Dublin). Israel: I. Yust,* D. Turner, and M. Burke (Tel Aviv); S. Pollack and G. Hassoun (Haifa); Z. Sthoeger (Rehovot); S. Maayan (Jerusalem). Italy: A. Chiesi* (Rome); R. Esposito and R. Borghi (Modena); C. Arici (Bergamo); R. Pristera (Bolzano); F. Mazzotta and A. Gabbuti (Firenze); V. Vullo and M. Lichtner (Rome); A. Chirianni and E. Montesarchio (Napoli); G. Antonucci, F. Iacomi, P. Narciso, and M. Zaccarelli (Rome); A. Lazzarin, R. Finazzi, and A. D’Arminio Monforte (Milan). Latvia: L. Viksna* (Riga). Lithuania: S. Chaplinskas* (Vilnius). Luxembourg: R. Hemmer* and T. Staub (Luxembourg). Netherlands: P. Reiss* (Amsterdam). Norway: J. Bruun,* A. Maeland, and V. Ormaasen (Oslo). Poland: B. Knysz* and J. Gasiorowski (Wroclaw); A. Horban (Warsaw); D. Prokopowicz and A. Wiercinska-Drapalo (Bialystok); A. Boron-Kaczmarska and M. Pynka (Szczecin); M. Beniowski and E. Mularska (Chorzow); H. Trocha (Gdansk). Portugal: F. Antunes* and E. Valadas (Lisbon); K. Mansinho (Lisbon); F. Matez (Lisbon). Romania: D. Duiculescu* and Victor Babes (Bucarest); A. Streinu-Cercel (Bucarest). Russia: E. Vinogradova and A. Rakhmanova (St. Petersburg). Serbia and Montenegro: D. Jevtovic* (Belgrade). Slovakia: M. Mokrás* and D. Staneková (Bratislava). Spain: J. González-Lahoz,* M. Sánchez-Conde, T. García-Benayas, L. Martin-Carbonero, and V. Soriano (Madrid); B. Clotet, A. Jou, J. Conejero, and C. Tural (Badalona); J. M. Gatell and J. M. Miró (Barcelona). Sweden: A. Blaxhult* (Solna); A. Karlsson (Stockholm); P. Pehrson (Huddinge). Switzerland: B. Ledergerber* and R. Weber (Zürich); P. Francioli and A. Telenti (Lausanne); B. Hirschel and V. Soravia-Dunand (Geneve); H. Furrer (Bern). Ukraine: E. Kravchenko* and N. Chentsova (Kyiv). United Kingdom: S. Barton* (London); A. M. Johnson and D. Mercey (London); A. Phillips, M.A. Johnson, and A. Mocroft (London); M. Murphy (London); J. Weber and G. Scullard (London); M. Fisher (Brighton); R. Brettle (Edinburgh). Virology group: C. Loveday and B. Clotet (central coordinators), plus ad-hoc virologists from participating sites in the EuroSIDA Study. Steering committee: Francisco Antunes, Anders Blaxhult, Nathan Clumeck, Jose Gatell, Andrzej Horban, Anne Johnson, Christine Katlama, Bruno Ledergerber (chair), Clive Loveday, Andrew Phillips, Peter Reiss, and Stefano Vella. Coordinating center staff: J. Lundgren (project leader), I. Gjørup, O. Kirk, N. Friis-Moeller, A. Mocroft, A. Cozzi-Lepri, W. Bannister, D. Mollerup, D. Podlevkareva, C. Holkmann Olsen, and J. Kjær

Collaborations in HIV Outcomes Research–US (4 sites)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 Study (1 site)Schlomo Staszewski, Eilke B. Helm, Amina Carlebach, Axel Müller, Annette Haberl, Gabi Nisius, Tessa Lennemann, Carsten Rottmann, Timo Wolf, Christoph Stephan, Markus Bickel, Manfred Mösch, Peter Gute, Leo Locher, Thomas Lutz, Stephan Klauke, and Gabi Knecht (clinical group); Hans W. Doerr and Martin Stürmer (virology group); Brenda Dauer (scientific advisor); Nils von Hentig (pharmacology group); Beverly Jennings (data management)

Aquitaine Cohort Study (6 sites)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: 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, and P. Blanco (Bordeaux University Hospital); P. Loste and L. Caunègre (Dax Hospital); F. Bonnal, S. Farbos, and M. Ferrand (Bayonne Hospital); J. Ceccaldi and S. Tchamgoué (Libourne Hospital); S. De Witte (Mont de Marsan Hospital); E. Buy (Villeneuve sur Lot Hospital)

HAART Observational Medical Evaluation and Research Cohort Study, British Columbia Centre for Excellence in HIV/AIDS (96 sites)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 Study (1 site)Jayne Ballinger, Sanjay Bhagani, Ronan Breen, Pat Byrne, Anne Carroll, Ian Cropley, Zoë Cuthbertson, Tony Drinkwater, Tom Fernandez, Anna Maria Geretti, Gabrielle Murphy, Dan Ivens, Margaret Johnson, Sabine Kinloch-de Loes, Marc Lipman, Sara Madge, Beth Prinz, Diane Robertson Bell, Sapna Shah, Leonie Swaden, Mervyn Tyrer, and Mike Youle (clinical group); Clinton Chaloner, Helen Gumley, Jackie Holloway, Dewi Puradiredja, Joyce Sweeney, and Robert Tsintas (data management); Wendy Bannister, Loveleen Bansi, Alessandro Cozzi-Lepri, Zoë Fox, Fiona Lampe, Amanda Mocroft, Andrew Phillips, Caroline Sabin, and Colette Smith (epidemiology/biostatistics group); Eric Amoah, Gillian Clewley, Louise Dann, Brendon Gregory, Ilesh Jani, George Janossy, Mel Kahan, Clive Loveday, and Mike Thomas (laboratory group)

South Alberta Clinic Cohort Study (1 site)John Gill and Ron Read

Köln/Bonn Cohort Study (2 sites)G. Fatkenheuer, J. Rockstroh, V. Schmeisser, K. Voigt, J. C. Wasmuth, and A. Wohrmann

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  1. J Infect Dis. (2006) 194 (5): 612-622. doi: 10.1086/506362
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