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To compare regimens consisting of either efavirenz or nevirapine and two or more nucleoside reverse transcriptase inhibitors (NRTIs) among HIV-infected, antiretroviral-naive, and AIDS-free individuals with respect to clinical, immunologic, and virologic outcomes.
Prospective studies of HIV-infected individuals in Europe and the US included in the HIV-CAUSAL Collaboration.
Antiretroviral therapy-naive and AIDS-free individuals were followed from the time they started an NRTI, efavirenz or nevirapine, classified as following one or both types of regimens at baseline, and censored when they started an ineligible drug or at 6 months if their regimen was not yet complete. We estimated the ‘intention-to-treat’ effect for nevirapine versus efavirenz regimens on clinical, immunologic, and virologic outcomes. Our models included baseline covariates and adjusted for potential bias introduced by censoring via inverse probability weighting.
A total of 15 336 individuals initiated an efavirenz regimen (274 deaths, 774 AIDS-defining illnesses) and 8129 individuals initiated a nevirapine regimen (203 deaths, 441 AIDS-defining illnesses). The intention-to-treat hazard ratios [95% confidence interval (CI)] for nevirapine versus efavirenz regimens were 1.59 (1.27, 1.98) for death and 1.28 (1.09, 1.50) for AIDS-defining illness. Individuals on nevirapine regimens experienced a smaller 12-month increase in CD4 cell count by 11.49 cells/μl and were 52% more likely to have virologic failure at 12 months as those on efavirenz regimens.
Our intention-to-treat estimates are consistent with a lower mortality, a lower incidence of AIDS-defining illness, a larger 12-month increase in CD4 cell count, and a smaller risk of virologic failure at 12 months for efavirenz compared with nevirapine.
The choice of an initial antiretroviral regimen is an important component in the care of an HIV-positive patient. The best initial regimens are the ones that are well tolerated, effective and take into account characteristics of the patient and the medications in order to maximize future treatment options. Clinical guidelines generally include regimens consisting of one non-nucleoside reverse transcriptase inhibitor (NNRTI) with two nucleoside reverse transcriptase inhibitors (NRTIs) among their recommended first-line regimens for the treatment of HIV.
Two of the most commonly prescribed NNRTIs are efavirenz and nevirapine. The WHO recommends regimens consisting of a NRTI backbone with either efavirenz or nevirapine . The European AIDS Clinical Society (EACS) and British HIV Association (BHIVA) guidelines also recommend both efavirenz and nevirapine, but specify when each is preferred [2,3]. Specifically, efavirenz is not recommended for women who are pregnant or may become pregnant due to potential teratogenic effects during the first trimester or for patients with psychiatric illness due to a possible higher prevalence of the side-effect dysphoria in this group. Nevirapine is not recommended for women with CD4 cell counts above 250 cells/μl and men with CD4 cell counts above 400 cells/μl at the time of treatment initiation because of an increased risk of serious hepatic events or for patients with existing hepatic impairments. The Department of Health and Human Services guidelines consider efavirenz to be the preferred NNRTI and nevirapine an acceptable NNRTI for some patients . Finally, the International AIDS Society (IAS) USA Panel guidelines list efavirenz as the only recommended NNRTI .
A pooled analysis of randomized clinical trials comparing efavirenz and nevirapine suggested a higher survival for efavirenz , but the analyses were based on few events (about 74 deaths) and the 95% confidence intervals (CIs) were wide. However, they found that efavirenz and nevirapine were similar with respect to virologic success, change in mean CD4 cell count, and clinical progression to AIDS.
Efavirenz and nevirapine have been compared in a number of observational studies. The majority of these studies suggest benefits of efavirenz over nevirapine. Those taking an efavirenz regimen had better immunologic responses [7,8], better virologic outcomes [7–13], and were less likely to develop clinical outcomes [7,12,14] than those taking a nevirapine regimen. Many of the individuals in these observational studies were new users of efavirenz and nevirapine, but were not necessarily antiretroviral therapy-naive .
In addition, none of the randomized or observational studies restricted their analyses to patients who were AIDS-free at the time of treatment initiation. Given the increasing proportion of patients initiating antiretroviral therapy without AIDS, it is important to compare regimens among those who are AIDS-free.
Using data from a large collaboration of observational studies from the US and Europe, we compare immunologic, virologic, and clinical outcomes between antire-troviral therapy-naive and AIDS-free patients who start a first-line regimen consisting of two or more NRTIs and either efavirenz or nevirapine.
The HIV-CAUSAL Collaboration has been described elsewhere . Briefly, the collaboration includes several prospective cohort studies from six European countries and the US: UK CHIC (UK), ATHENA (Netherlands), FHDH-ANRS CO4 (France), SHCS (Switzerland), PISCIS (Spain), CoRIS/CoRIS-MD (Spain), VACS-VC (US veterans), AMACS (Greece), UK Register of HIV Seroconverters (UK), ANRS PRIMO (France), ANRS SEROCO (France), and GEMES (Spain).
All cohorts included in the HIV-CAUSAL Collaboration were assembled prospectively and are based on data collected for clinical purposes within national healthcare systems with universal access to care. Each cohort in the collaboration collects data prospectively including all CD4 cell counts, HIV RNAs, treatment initiations, AIDS-defining illnesses, and deaths.
For each individual, follow-up started at the initiation of an eligible antiretroviral medication (baseline). Our analysis was restricted to HIV-infected individuals who met the following eligibility criteria at baseline dates between 1998 and 2009: age 18 years or older, previously antiretroviral therapy-naive, no history of an AIDS-defining illness , no pregnancy (when information was available), and CD4 cell count and HIV RNA measurements within 6 months of each other. For the analysis of clinical outcomes (see below), follow-up ended at the occurrence of the outcome, censoring, loss to follow-up [12 months after the most recent laboratory measurement or pregnancy (if known)], or the cohort-specific administrative end of follow-up (ranging from December 2003 to September 2009), whichever occurred earliest. For the analysis of immunologic and virologic outcomes (see below), follow-up ended at 12 ± 2 months after baseline.
We considered clinical, immunologic, and virologic outcomes. The clinical outcomes of interest were death from any cause and clinical AIDS-defining illness  or death. The date of death was identified using a combination of national and local mortality registries and clinical records as described elsewhere , and AIDS-defining illnesses were ascertained by the treating physicians.
The immunologic outcome of interest was the 12-month change in CD4 cell count after baseline. If CD4 cell count was not measured exactly 12 months after baseline, we used the closest measurement within 2 months. Similarly, the virologic outcome of interest was virologic failure (HIV RNA >50 copies/ml) at 12 ± 2 months. In a sensitivity analysis, we defined virologic failure as HIV RNA above 400 copies/ml.
We compared antiretroviral therapy-naive individuals with respect to their first-line antiretroviral regimen. Individuals were not required to start all of the drugs in their regimen on the same day. Instead, we allowed a grace period for them to complete one of the regimens of interest. Although our unweighted estimates did not vary for grace periods between 0 and 6 months, we used 6 months for efficiency purposes. Individuals were followed from the time they started the first drug in their regimen (baseline) and were censored if and when they started an ineligible drug or at 6 months if their regimen was not complete by that time.
We considered two types of first-line regimens: efavirenz and nevirapine-based NNRTI regimens in combination with a backbone of two or more NRTIs. Individuals who started an ineligible drug (i.e. a protease inhibitor, an integrase inhibitor, a fusion inhibitor, or a NNRTI other than efavirenz and nevirapine) at baseline were classified as following neither type of regimen and were excluded. Those starting both efavirenz and nevirapine at baseline were also excluded.
Individuals who started either efavirenz or nevirapine (and possibly one or more NRTIs) at baseline were classified as following either efavirenz regimens or nevirapine regimens. Those who started one or more NRTIs, but neither NNRTI at baseline, were classified as following both types of regimens because these individuals still had 6 months to start either efavirenz or nevirapine and complete one of the types of regimens of interest. We created an expanded dataset in which we replicated individuals who followed both types of regimens at baseline. From this point forward, individuals refer to replicates in the expanded dataset. To prevent bias, one individual in the expanded dataset was classified as following efavirenz regimens and the other individual was classified as following nevirapine regimens .
As mentioned above, if individuals started an ineligible drug within 6 months of baseline and before their regimen was complete, they were artificially censored at the time the ineligible drug was initiated. For those initiating only NRTIs at baseline and, therefore, following both types of regimens at baseline, different drugs were considered ineligible for each individual in the expanded dataset. Specifically, in addition to the ineligible drugs listed above, efavirenz is an ineligible drug for the nevirapine regimens and vice versa. Individuals were censored at 6 months from baseline if their regimen was not yet complete.
For the two clinical outcomes, we fit separate pooled logistic models to the expanded dataset to estimate the hazard ratio of the outcome for nevirapine versus efavirenz regimens. Both models included a regimen indicator (1: nevirapine, 0: efavirenz), cohort, month of follow-up (modeled as a restricted cubic spline with 4 knots at 1, 6, 24, and 60 months), and the following baseline covariates: sex, age (<35, 35–49, ≥50 years), race (white, black, other or unknown), geographic origin (Western countries, sub-Saharan Africa, other, or unknown), mode of transmission (heterosexual, homosexual/bisexual, injection drug use, other or unknown), CD4 cell count (<200, 200–299, 300–399, 400–499, ≥500), HIV-1 RNA (<10 000, 10 000–100 000, >100 000 copies/ml), calendar year (1998, 1999–2000, 2001–2003, ≥2004), years since HIV diagnosis (<1, 1–4, ≥5 years, unknown), and an indicator for starting only NRTIs at baseline. For the immunologic outcome, we fit a linear regression model with the same covariates to estimate the 12-month change in CD4 cell count for nevirapine versus efavirenz regimens among those with measurements at 12 ± 2 months. For the virologic outcome, we fit a Poisson regression model with the same covariates to estimate the risk ratio of virologic failure at 12 months for nevirapine versus efavirenz regimens among those with measurements at 12 ± 2 months.
To adjust for potential selection bias due to the artificial censoring, we used inverse probability weighting in all models above. We estimated the weights in the expanded dataset via pooled logistic models for artificial censoring that included the time-fixed covariates and time-varying CD4 cell count (restricted cubic spline with 5 knots at 10, 200, 350, 500, and 100 cells/μl), HIV-1 RNA (<10 000, 10 000–100 000, >100 000 copies/ml), AIDS-defining illness (when the outcome was death alone), and time since last laboratory measurement (0, 1–2, 3–4, 5–6, ≥7 months). We fitted the weight models separately by regimen type and by the type of artificial censoring (censoring due to starting an ineligible drug and censoring due to not completing a regimen by 6 months).
Under the assumption that we successfully adjusted for all confounders, the estimated coefficient for the regimen indicator in the weighted models can be interpreted as the ‘intention-to-treat’ effect that would have been estimated from a randomized trial with similar adherence and loss to follow-up. For efficiency, the weights were truncated at the 99th percentile . Appendix Table 1 shows estimates from unweighted models with and without the baseline covariates, and from models weighted with unstabilized and nontruncated weights.
For the two clinical outcomes, we also estimated absolute risks by fitting weighted models like the one described above that also included product (interaction) terms between the regimen indicator and month of follow-up with spline terms. The model’s predicted values were then used to estimate the 5-year survival and 5-year AIDS-free survival curves from baseline. A nonparametric bootstrap with 500 samples was used to compute 95% CIs for the survival estimates.
Several sensitivity analyses were also performed. For all four outcomes, we used continuous as opposed to categorical baseline covariates, restricted the analysis to those for which nevirapine is recommended (i.e. CD4 cell count <400 in men and <250 in women), and included chronic hepatitis C infection as a baseline covariate in cohorts with information on hepatitis C infection. For the immunologic and virologic outcomes, we also weighted by the inverse probability of remaining alive, remaining uncensored due to infrequent laboratory measurements, and having a measurement at 12 ± 2 months after baseline. None of these sensitivity analyses yielded appreciably different results (data not shown).
All analyses were conducted with SAS 9.3 (SAS Institute, Cary, North Carolina, USA).
Of the 19 863 therapy-naive HIV-infected patients who initiated an eligible regimen at baseline, 11 734 initiated efavirenz, 4527 initiated nevirapine, and 3602 initiated only NRTIs at baseline. The expanded dataset included 23 465 (11 734 + 4527 + 2 × 3602) individuals of which 15 336 (11 734 + 3602) followed an efavirenz regimen and 8129 (4527 + 3602) followed a nevirapine regimen. Figure 1 shows the path of individuals of each regimen type during the first 6 months of follow-up. Of the 23 465 individuals in the death analysis, 61.9% initiated a complete regimen at baseline, 5.8% were censored due to starting an ineligible drug, 27.6% were censored due to not completing a regimen by 6 months, 0.2% died without completing a regimen or being censored, 0.5% were lost to follow-up without completing a regimen or being censored, 1.7% reached their administrative end of follow-up without completing a regimen or being censored, and an additional 2.3% completed a regimen between 1 and 6 months from baseline. The proportions in the AIDS or death analysis were similar.
Table 1 shows the characteristics of the study population by regimen type at baseline. Men, those with the lowest baseline CD4 cell counts, those with the highest baseline HIV-1 RNAs, those starting treatment after 2003, and those with chronic hepatitis C infection were more likely to initiate efavirenz than nevirapine. The median [interquartile range (IQR)] follow-up time in the death analysis was 18 (6, 44) months for the efavirenz regimens and 11 (6, 49) months for the nevirapine regimens. The median (IQR) follow-up time in the AIDS or death analysis was 17 (6, 42) months for the efavirenz regimens and 10 (6, 46) months for the nevirapine regimens. Appendix Table 2 shows the number and percentage of individuals taking recommended (abacavir/lamivudine, tenofovir/emtricitabine, zidovudine/lamivudine, teno-fovir/lamivudine) [1–5] and other NRTI backbones by regimen type at baseline.
As shown in Table 2, 274 and 203 died and 774 and 441 developed an AIDS-defining illness or died among those initiating an efavirenz and a nevirapine regimen, respectively. The hazard ratios for progression to death, and AIDS or death are also given in Table 2. Compared with the efavirenz regimens, the mortality hazard ratio (95% CI) for the nevirapine regimens was 1.59 (1.27, 1.98). Compared with the efavirenz regimens, the AIDS or death hazard ratio (95% CI) for the nevirapine regimens was 1.28 (1.09, 1.50).
Table 2 also shows the 12-month adjusted mean change in CD4 cell count and the number with virologic failure at 12 ±2 months. Compared with the efavirenz regimens, the change in the CD4 cell count (95% CI) for the nevirapine regimens was −11.49 (−18.13, −4.86). The mean CD4 cell count would have increased from 285 to 455 cells/μl over 12 months had all individuals taken the efavirenz regimens, and from 285 to 443 cells/μl had all individuals taken the nevirapine regimens.
Among those initiating efavirenz and nevirapine regimens, 23 and 36% had virologic failure (HIV-1 RNA >50 copies/ml) at 12 months, respectively. Compared with the efavirenz regimens, the risk ratio of virologic failure for the nevirapine regimens was 1.52 (1.27, 1.81).
Figure 2a plots 5-year survival from baseline for the efavirenz and nevirapine regimens. The survival proportion was 97.2% (96.6%, 97.7%) for the efavirenz regimens and 94.8% (92.8%, 96.7%) for the nevirapine regimens. The 5-year survival difference was −2.40% (−4.08%, −0.72%).
Figure 2b plots 5-year AIDS-free survival from baseline for the efavirenz and nevirapine regimens. The AIDS-free survival proportion was 93.1% (92.4%, 93.8%) for the efavirenz regimens and 90.3% (88.0%, 92.5%) for the nevirapine regimens. The 5-year AIDS-free survival difference was −2.81% (−4.89%, −0.73%). Survival and AIDS-free survival are similar for both regimens for the first 2 years and then diverge.
In subset analyses, the mortality hazard ratio was 1.43 (1.06, 1.92) when we restricted to baseline calendar years 2001 and beyond, 1.64 (1.30, 2.07) when we restricted to men, 1.42 (1.30, 2.07) when we restricted to those with baseline CD4 cell count below 200 cells/μl, and 1.33 (0.95, 1.84) when we restricted to those with baseline viral load above 100 000 copies/ml. When we define virologic failure as HIV RNA above 400 copies/ml, the risk ratio increases to 1.78 (1.37, 2.30) comparing nevirapine with efavirenz (see Appendix Table 1).
We estimated the effects of nevirapine versus efavirenz on immunologic, virologic, and clinical outcomes. Those on nevirapine regimens had a 11 cell/μl smaller 12-month increase in CD4 cell count, were 52% more likely to not be virologically suppressed at 12 months, 28% more likely to develop an AIDS-defining illness or die, and 59% more likely to die than those on efavirenz regimens.
We designed our observational analysis to emulate the intention-to-treat analysis of a randomized clinical trial in which antiretroviral-naive, AIDS-free adults are randomized to receive two NRTIs and either efavirenz or nevirapine. Several randomized clinical trials with a similar design, but which did not exclude individuals with AIDS at baseline, were included in a recently published meta-analysis . This pooled analysis, however, includes two trials of individuals with tuberculosis [19,20], and one trial which included patients who were also taking a protease inhibitor . We repeated the meta-analysis excluding this latter trial and pooling trials with both dosings of nevirapine (200 mg twice daily and 400 mg once daily). There were 9 and 27 deaths out of 560 and 763 patients in the efavirenz and nevirapine arms, respectively. The mortality relative risk (95% CI) for nevirapine compared with efavirenz regimens was 1.97 (0.95, 4.07).
Both the meta-analysis of randomized trials and our analysis of observational data found an increase in mortality among initiators of nevirapine, compared with efavirenz, regimens. However, our result was more precise and directly applicable to HIV-infected individuals who are identified before an AIDS-defining illness is diagnosed. One possible explanation for our findings is that nevirapine regimens may be more frequently interrupted due to toxicities. If these patients switch to a second-line regimen that is less effective and harder to tolerate, nevirapine regimens will appear less effective than efavirenz regimens in an intention-to-treat analysis, particularly in later years.
Our mortality hazard ratio (1.59) was attenuated in comparison with that in the meta-analysis of randomized trials (1.97). The apparent attenuation of the effect may be due to greater random variability in the randomized trials estimate, different switching patterns in the randomized and observational studies, or confounding in our observational study. Our estimates would be confounded if we had failed to adjust for prognostic factors that also predict the choice of NNRTI (nevirapine or efavirenz). For example, those initiating antiretroviral therapy in later calendar years were more likely to initiate efavirenz than nevirapine. If other (unmeasured) aspects of HIV care improved over time, the estimated differences might be partly attributable to factors other than the NNRTI. However, our analyses are adjusted for calendar year and our estimates did not appreciably change when we restricted the analyses to those initiating in 2001 or later.
The choice of NRTI backbone is another potential confounder. In both randomized clinical trials, efavirenz and nevirapine were compared to a constant backbone of two NRTIs. In our study, we compared efavirenz and nevirapine regimens with any backbone of two or more NRTIs. The backbones consisting of zidovudine/lamivudine and tenofovir/emtricitabine were more frequently used with efavirenz than nevirapine, whereas the backbones of abacavir/lamivudine and tenofovir/lamivudine were used equally with both NNRTIs among those initiating a complete regimen at baseline. We did not have enough data for a meaningful analysis of different backbones. The choice of NRTI backbone may affect our results if certain backbones are associated with the outcome and are more often paired with one NNRTI than the other.
In addition, during the course of this study, both drugs may have been used in a way that is no longer considered optimal. Specifically, efavirenz is contraindicated for patients with psychiatric illness and pregnant women, whereas nevirapine is not recommended for patients with high CD4 cell counts or those with hepatic impairments. Whereas our data did not allow us to investigate psychiatric illness, we excluded women known to be pregnant in all analyses and conducted sensitivity analyses restricted to those with baseline CD4 cell counts for which nevirapine is recommended and included chronic hepatitis C infection as a baseline covariate, and saw no appreciable differences in the results.
Previous observational analyses did not explicitly try to emulate the same randomized trial as we did and, therefore, our results are not directly comparable with theirs. Specifically, some studies included pretreated individuals [7,13], many included individuals with prior AIDS-defining illnesses [7–14], and none simultaneously considered the same clinical, virologic, and immunologic outcomes as we did. Further, more subtle differences in inclusion criteria, exposure definitions, and statistical analysis make direct comparisons difficult.
Yet our findings with respect to clinical outcomes were similar to those of previous observational studies which included patients with AIDS at baseline. The ART-CC  found that those on nevirapine were 65% more likely to die than those on efavirenz. Nachega et al.  reported a greater than two-fold increase in the risk of death for those on nevirapine compared with efavirenz. In both studies, the 95% CI was wide.
Most observational studies that considered virologic outcomes also found that efavirenz was superior to nevirapine. Compared with individuals taking efavirenz, individuals taking nevirapine were less likely to achieve an undetectable viral load [10,14] and more likely to experience virologic failure [9,12]. Individuals taking nevirapine also reached virologic failure faster [8,10,12] and an undetectable viral load slower [9,12] than those taking efavirenz. Regarding immunologic outcomes, previous observational studies found that those taking efavirenz and nevirapine had similar times to a 50 cell/μl or larger increase in CD4 cell count  and similar increases in CD4 cell count [12,13].
As a result of recent changes to the clinical guidelines, an increasing proportion of patients without an AIDS-defining illness are starting treatment. Previous studies have combined those initiating with and without AIDS in their analyses of first-line regimens. Our results have important clinical implications for patients initiating treatment without AIDS. In these patients, we find that regimens containing efavirenz perform better than regimens containing nevirapine with respect to immunologic, virologic, and clinical outcomes.
Writing Committee: Lauren E. Cain (Coordinating Center), Andrew Phillips, Sara Lodi (UKRHS), Caroline Sabin, Loveleen Bansi (UK CHIC), Amy Justice, Janet Tate (VACS), Roger Logan, James M. Robins, Jonathan A. C. Sterne (Coordinating Center), Ard van Sighem, Frank de Wolf (ATHENA), Heiner C. Bucher, Luigia Elzi (SHCS), Giota Touloumi, Georgia Vourli (AMACS), Anna Esteve, Jordi Casabona (PISCIS), Julia del Amo, Santiago Moreno (CoRIS/CoRIS-MD), Rémonie Seng, Laurence Meyer (ANRS PRIMO/SEROCO), Santiago Pérez-Hoyos, Roberto Muga (GEMES), Sophie Abgrall, Dominique Costagliola (FHDH-ANRS CO4), and Miguel A. Hernán (Coordinating Center).
UK CHIC: Steering committee: J. Ainsworth, J. Anderson, A. Babiker, L. Bansi, D. Chadwick, V. Delpech, D. Dunn, M. Fisher, B. Gazzard, R. Gilson, M. Gompels, T. Hill, M. Johnson, C. Leen, M. Nelson, C. Orkin, A. Palfreeman, A. Phillips, D. Pillay, F. Post, C. Sabin (PI), M. Sachikonye, A. Schwenk, J. Walsh. Central coordination: UCL, London (L. Bansi, T. Hill, S. Huntington, A. Phillips, C. Sabin); Medical Research Council Clinical Trials Unit (MRC CTU), London (D. Dunn, A. Glabay). Participating centres: Barts and The London NHS Trust, London (C. Orkin, N. Garrett, J. Lynch, J. Hand, C. de Souza); Brighton and Sussex University Hospitals NHS Trust (M. Fisher, N. Perry, S. Tilbury, D. Churchill); Chelsea and Westminster NHS Trust, London (B. Gazzard, M. Nelson, M. Waxman, D. Asboe, S. Mandalia); Health Protection Agency Centre for Infections, London (HPA) (V. Delpech); Homerton University Hospital NHS Trust, London (J. Anderson, S. Munshi); King’s College Hospital NHS Foundation Trust, London (F. Post, H. Korat, C. Taylor, Z. Gleisner, F. Ibrahim, L. Campbell Mortimer Market Centre, London (R. Gilson, N. Brima, I. Williams); North Middlesex University Hospital NHS Trust, London (A. Schwenk, J. Ainsworth, C. Wood, S. Miller); Royal Free NHS Trust and UCL Medical School, London (M. Johnson, M. Youle, F. Lampe, C. Smith, H. Grabowska, C. Chaloner, D. St. Mary’s Hospital, London (J. Walsh, J. Weber, F. Ramzan, N. Mackie, A. Winston); The Lothian University Hospitals NHS Trust, Edinburgh (C. Leen, A. Wilson); North Bristol NHS Trust (M. Gompels, S. Allan); University of Leicester NHS Trust (A. Palfreeman, A. Moore); South Tees Hospitals NHS Foundation Trust (D. Chadwick, K. Wakeman).
Director: F. de Wolf, HIV Monitoring Foundation, Amsterdam. Data analysis group: D.O. Bezemer, L.A.J. Gras, A.M. Kesselring, A.I. van Sighem, C. Smit, S. Zhang. Data collection: S. Zaheri. Participating centres (*site coordinating physicians): Academic Medical Centre of the University of Amsterdam, Amsterdam (J.M. Prins*, K. Boer, J.C. Bos, S.E. Geerlings, M.H. Godfried, M.E. Haverkort, T.W. Kuijpers, J.M.A. Lange, J.T.M. van der Meer, F.J.B. Nellen, D. Pajkrt, T. van der Poll, P. Reiss, H.J. Scherpbier, M. van der Valk, S.M.E. Vrouenraets, M. van Vugt, F.W.M.N. Wit), Academic Hospital Maastricht, Maastricht (G. Schreij*, S. Lowe, A. Oude Lashof), Catharina Hospital, Eindhoven (B. Bravenboer*, M.J.H. Pronk), Erasmus Medical Centre, Rotterdam (M.E. van der Ende*, M. van der Feltz, L.B.S. Gelinck, J.L. Nouwen, B.J.A. Rijnders, E.D. de Ruiter, L. Slobbe, C.A.M. Schurink, A. Verbon, T.E.M.S. de Vries-Sluijs), Erasmus Medical Centre Sophia, Rotterdam (G. Driessen, N.G. Hartwig), Flevo Hospital, Almere (J. Branger), Haga Hospital, location Leyenburg, Den Haag (R.H. Kauffmann*, E.F. Schippers), Isala Clinics, Zwolle (P.H.P. Groeneveld*, M.A. Alleman, J.W. Bouwhuis), Kennemer Gasthuis, Haarlem (R.W. ten Kate*, R. Soetekouw), Leiden University Medical Centre, Leiden (F.P. Kroon*, S.M. Arend, M.G.J. de Boer, P.J. van den Broek, J.T. van Dissel, H. Jolink, C. van Nieuwkoop), Maasstadziekenhuis, location Clara, Rotterdam (J.G. den Hollander*, K. Pogany), Medical Centre Alkmaar, Alkmaar (W. Bronsveld*, W. Kortmann, G. van Twillert), Medical Centre Haaglanden, location Westeinde, Den Haag (R. Vriesendorp*, E.M.S. Leyten), Medical Centre Leeuwarden, Leeuwarden (D. van Houte*, M.B. Polée, M.G.A. van Vonderen), Medisch Spectrum Twente, Enschede (C.H.H. ten Napel*, G.J. Kootstra), Onze Lieve Vrouwe Gasthuis, Amsterdam (K. Brinkman*, G.E.L. van den Berk, W.L. Blok, P.H.J. Frissen, W.E.M. Schouten), Medical Centre Jan van Goyen, Amsterdam (A. van Eeden*, D.W.M. Verhagen), Slotervaart Hospital, Amsterdam (J.W. Mulder*, E.C.M. van Gorp, P.M. Smit, S. Weijer), St Elisabeth Hospital, Tilburg (J.R. Juttmann*, A.E. Brouwer, M.E.E. van Kasteren), St Lucas Andreas Hospital, Amsterdam (J. Veenstra*, K.D. Lettinga), Radboud University Nijmegen Medical Centre, Nijmegen (P.P. Koopmans*, A.M. Brouwer, A.S.M. Dofferhoff, M. van der Flier, R. de Groot, H.J.M. ter Hofstede, M. Keuter, A.J.A.M. van der Ven), University Medical Centre Groningen, Groningen (H.G. Sprenger*, S. van Assen, R. Doedens, E.H. Scholvinck, C.J. Stek), University Medical Centre Utrecht, Utrecht (A.I.M. Hoepelman*, J.E. Arends, P.M. Ellerbroek, J.C.H. van der Hilst, C.A.J.J. Jaspers, L.J. Maarschalk-Ellerbroek, J.J. Oosterheert, E.J.G. Peters, T. Mudrikova, M.M.E. Schneider, M.W.M. Wassenberg), Wilhelmina Children’s Hospital, Utrecht (S.P.M. Geelen, T.F.W. Wolfs), Free University Medical Centre, Amsterdam (S.A. Danner*, M.A. van Agtmael, W.F.W. Bierman, F.A.P. Claessen, E.V. de Jong, W. Kortmann, R.M. Perenboom, E.A. bij de Vaate), Hospital Rijnstate, Arnhem (C. Richter*, J. van der Berg, E.H. Gisolf), Hospital Walcheren, Vlissingen (M. van den Berge*, A. Stegeman), Sint Elisabeth Hospitaal, Willemstad, Curaçao (A.J. Duits, K. Winkel).
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, N. Viget. DMI2 coordinating center: French Ministry of Health (Valérie Salomon), Technical Hospitalization Information Agency, ATIH (N. Jacquemet). Statistical analysis center: U943 INSERM et UPMC (S. Abgrall, D. Costagliola, S. Grabar, M. Guiguet, E. Lanoy, L. Lièvre, M. Mary-Krause, H. Selinger-Leneman), INSERM Transfert (J.M. Lacombe, V. Potard). COREVIH: Paris area: Corevih Ile de France Centre (G.H. Pitié-Salpétrière: F. Bricaire, S. Herson, C. Katlama, A. Simon; Hôpital Saint-Antoine: N. Desplanque, P.M. Girard, J.L. Meynard, M.C. Meyohas, O. Picard; Hôpital Tenon: J. Cadranel, C. Mayaud, G. Pialoux), Corevih Ile de France Est (Hôpital Saint-Louis: J.P. Clauvel, J.M. Decazes, L. Gerard, J.M. Molina; G.H. Lariboisière-Fernand Widal: M. Diemer, P. Sellier; Hôpital Avicenne: M. Bentata, P. Honoré; Hôpital Jean Verdier: V. Jeantils, S. Tassi; Hôpital Delafontaine: D. Mechali, B. Taverne), Corevih Ile de France Nord (Hôpital Bichat-Claude Bernard: E. Bouvet, B. Crickx, J.L. Ecobichon, S. Matheron, C. Picard-Dahan, P. Yeni), Corevih Ile de France Ouest (Hôpital Ambroise Paré: H. Berthé, C. Dupont; Hôpital Louis Mourier: C. Chandemerle, E. Mortier; Hôpital Raymond Poincaré: P. de Truchis), Corevih Ile de France Sud (Hôpital Européen Georges Pompidou: D. Tisne-Dessus, L. Weiss; G.H. Tarnier-Cochin: D. Salmon; Hôpital Saint-Joseph: I. Auperin, J. Gilquin; Hôpital Necker adultes: L. Roudière, J.P. Viard; Hôpital Antoine Béclère: F. Boué, R. Fior; Hôpital de Bicêtre: J.F. Delfraissy, C. Goujard; Hôpital Henri Mondor: C. Jung, Ph Lesprit; Hôpital Paul Brousse: D. Vittecoq). Outside Paris area: Corevih Alsace (CHRU de Strasbourg: P. Fraisse, J.M. Lang, D. Rey; C.H. de Mulhouse: G. Beck-Wirth), Corevih de l’Arc Alpin (C.H.U. de Grenoble: J.P. Stahl, P. Lecercq), Corevih Auvergne-Loire (C.H.U. de Clermont-Ferrand: F. Gourdon, H. Laurichesse; C.H.R.U. de Saint-Etienne: A. Fresard, F. Lucht); Corevih Basse-Normandie (C.H.R.U. de Caen: C. Bazin, R. Verdon), Corevih Bourgogne (C.H.R.U. de Dijon: P. Chavanet), Corevih Bretagne (C.H.U. de Rennes: C. Arvieux, C. Michelet), Corevih Centre (C.H.R.U. de Tours: P. Choutet, A. Goudeau, M.F. Maître), Corevih Franche-Comté (C.H.R.U. de Besançon: B. Hoen; C.H. de Belfort: P. Eglinger, J.P. Faller); Corevih Haute-Normandie (C.H.R.U. de Rouen: F. Borsa-Lebas, F. Caron), Corevih Languedoc-Roussillon (C.H.U. de Montpellier: J. Reynes; C.H.G. de Nîmes: J.P. Daures), Corevih Lorraine (Nancy Hôpital de Brabois: T. May, C. Rabaud; C.H.R.U. de Reims: J.L. Berger, G. Rémy), Corevih de Midi-Pyrénés (Toulouse C.H.U. Purpan: E. Arlet-Suau, L. Cuzin, P. Massip, M.F. Thiercelin Legrand; Toulouse Hôpital la Grave: G. Pontonnier; Toulouse C.H.U. Rangueil), Corevih Nord-Pas de Calais (C.H. de Tourcoing: N. Viget, Y. Yasdanpanah), Corevih PACA Est (Nice Hôpital Archet 1: P. Dellamonica, C. Pradier, P. Pugliese; C.H.G. Antibes-Juan les Pins: K. Aleksandrowicz, D. Quinsat), Corevih PACA Ouest (Marseille Hôpital de la Conception: I. Ravaux, H. Tissot-Dupont; Marseille Hôpital
J.P. Delmont, J. Moreau; Marseille Institut Paoli Calmettes: J.A. Gastaut; Marseille Hôpital Sainte-Marguerite: I. Poizot-Martin, F. Retornaz, J. Soubeyrand; Marseille Centre pénitentiaire des Baumettes: A. Galinier, J.M. Ruiz; C.H.G. d’Aix-En-Provence: T. Allegre, P.A. Blanc; C.H. d’Arles: D. Bonnet-Montchardon; C.H. d’Avignon: G. Lepeu; C.H. de Digne Les Bains: P. Granet-Brunello; C.H. de Gap: J.P. Esterni, L. Pelissier; C.H. de Martigues: R. Cohen-Valensi, M. Nezri; C.H.I. de Toulon: S. Chadapaud, A. Laffeuillade), Corevih Pays de la Loire (C.H.R.U. de Nantes: E. Billaud, F. Raffi), Corevih de la Vallée du Rhône (Lyon Hôpital de la Croix-Rousse: A Boibieux, D. Peyramond; Lyon Hôpital Edouard Herriot: J.M. Livrozet, J.L. Touraine; Lyon Hôtel-Dieu: L. Cotte, C. Trepo). Overseas: Corevih Guadeloupe (C.H.R.U. de Pointe-à-Pitre: M. Strobel; C.H. Saint-Martin: F. Bissuel), Corevih Guyane (C.H.G. de Cayenne: R. Pradinaud, M. Sobesky), Corevih Martinique (C.H.R.U. de Fort-de-France: A. Cabié), Corevih de La Réunion (C.H.D. Félix Guyon: C. Gaud, M. Contant).
C. Aebi, M. Battegay, E. Bernasconi, J. Böni, P. Brazzola, H.C. Bucher, Ph. Bürgisser, A. Calmy, S. Cattacin, M. Cavassini, J.-J. Cheseaux, G. Drack, R. Dubs, M. Egger, L. Elzi, M. Fischer, M. Flepp, A. Fontana, P. Francioli (President of the SHCS, Centre Hospitalier Universitaire Vaudois, CH-1011- Lausanne), H.J. Furrer, C. Fux, A. Gayet-Ageron, S. Gerber, M. Gorgievski, H. Günthard, Th. Gyr, H. Hirsch, B. Hirschel, I. Hösli, M. Hüsler, L. Kaiser, Ch. Kahlert, U. Karrer, C. Kind, Th. Klimkait, B. Ledergerber, G. Martinetti, B. Martinez, N. Müller, D. Nadal, F. Paccaud, G. Pantaleo, L. Raio, A. Rauch, S. Regenass, M. Rickenbach, C. Rudin (Chairman of the MoChiV Substudy, Basel UKBB, Römergasse 8, CH-4058 Basel), P. Schmid, D. Schultze, J. Schüpbach, R. Speck, P. Taffé, A. Telenti, A. Trkola, P. Vernazza, R. Weber, C.-A. Wyler, S. Yerly.
Coordinators: J. Casabona, Centre d’Estudis Epidemiològics les Infeccions de Transmissió Sexual i Sida de Catalunya (CEEISCAT), Jose M. Miró (Hospital Clínic de Barcelona-Idibaps, Universitat de Barcelona). Field coordinator: A. Gallois (CEEISCAT). Steering committee: J. Casabona, A. Gallois, A. Esteve (CEEISCAT), Jose M. Miró (Hospital Clínic de Barcelona-Idibaps, Universitat de Barcelona), D. Podzamczer (Hospital de Bellvitge de Barcelona), J. Murillas (Hospital Son Espases). Scientific committee: J.M. Gatell, C. Manzardo (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), M. Riera (Hospital Son Espases), F. Segura, G. Navarro (Corporación Sanitaria Universitaria Parc Taulí, Universitad Autónoma de Barcelona), L. Force (Hospital de Mataró), J. Vilaró (Hospital General de Vic), A. Masabeu (Hospital de Palamós), I. García (Hospital General d’Hospitalet), M. Guadarrama (Hospital Alt Penedès de Vilafranca), C. Cifuentes (Hospital Son Llàtzer), D. Dalmau, À *. Jaen (Hospital Universitari Mútua de Terrassa), C. Agustí (CEEISCAT). Data Management and statistical analysis: A. Esteve, A. Montoliu (CEEIS-CAT), I. Pérez (Hospital Clínic- Idibaps, Universitat de Barcelona). Technical support: I. Pérez (Hospital Clínic de Barcelona- Idibaps, Universitat de Barcelona), Freyra Gargoulas (Hospital Son Espases and Hospital Son Llàtzer). Clinicians involved: J.L. Blanco, F. Garcia-Alcaide, E. Martínez, 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. Saumoy, A. Imaz, J.M. Tiraboschi, O. Murillo, F. Bolao, C. Peña, C. Cabellos, M. Masó, A. Vila (Hospital Universitari de Bellvitge), M. Sala, M. Cervantes, Ma Jose Amengual, M. Navarro, E Penelo (Corporación Sanitaria Universitaria Parc Taulí, Universitad Autónoma de Barcelona), P. Barrufet, G. Bejarano (Hospital de Mataró, Barcelona), J. Molina, M. Guadarrama, M. Alvaro, J. Mercadal (Hospital Alt Penedès de Vilafranca). Civil society representatives: Juanse Fernández (Comitè 1er de Desembre), Jesús E. Ospina (RedVIH).
Steering committee: J. Berenguer, J. del Amo, F. García, F. Gutiérrez, P. Labarga, S. Moreno, M.A. Muñoz. Field work, data management, and statistical analyses: A.M. Caro-Murillo, P. Sobrino, I. Jarrín. Participating centres: Hospital Universitario de Canarias, Santa Cruz de Tenerife (J.L. Gómez Sirvent, P. Rodríguez, M.R. Alemán, M.M. Alonso, A.M. López, M.I. Hernández), Hospital Carlos III, Madrid (V. Soriano, P. Labarga, P. Barreiro, J. Medrano, P. Rivas, D. Herrero, F. Blanco, M.E. Vispo, L. Martín, G. Ramírez, M. de Diego), Hospital Doce de Octubre, Madrid (R. Rubio, F. Pulido, V. Moreno, C. Cepeda, Rl. Hervás), Hospital Donostia, San Sebastián (J.A. Iribarren, J. Arrizabalaga, M.J. Aramburu, X. Camino, F. Rodríguez-Arrondo, M.A. von Wichmann, L. Pascual, M.A. Goenaga), Hospital General Universitario de Elche (F. Gutiérrez, M. Masiá, J.M. Ramos, S. Padilla, V. Sánchez-Hellín, E. Bernal, C. Escolano, F. Montolio, Y. Peral), Hospital Gregorio Marañón, Madrid (J. Berenguer, J.C. López, P. Miralles, J. Cosín, M. Sánchez, I. Gutiérrez, M. Ramírez, B. Padilla), Hospital Universitari de Tarragona Joan XXIII (F. Vidal, M. Sanjuan, J. Peraire, S. Veloso, C. Viladés, M. López-Dupla, M. Olona, M. Vargas), Hospital La Fe, Valencia (J.L. Aldeguer, M. Blanes, J. Lacruz, M. Salavert, M. Montero, S. Cuéllar), Hospital de la Princesa, Madrid (I. de los Santos, J. Sanz), Hospital San Pedro, Logroño (J.A. Oteo, J.R. Blanco, V. Ibarra, L. Metola, M. Sanz, L. Pérez-Martínez), Hospital de Navarra, Pamplona (J. Sola, J. Uriz, J. Castiello, J. Reparaz, M.J. Arriaza, C. Irigoyen), Hospital Ramón y Cajal, Madrid (S. Moreno, A. Antela, J.L. Casado, F. Dronda, A. Moreno, M.J. Pérez, D. López, C. Gutiérrez, B. Hernández, M. Pumares, P. Martí, L. García, C. Page), Hospital San Cecilio, Granada (F. García, J. Hernández, A. Peña, L. Muñoz, J. Parra), Hospital Universitario Virgen del Rocío, Sevilla (P. Viciana, M. Leal, L.F. López-Cortés, M. Trastoy, R. Mata).
Consortium PI: A.C. Justice; Scientific Officer (NIAAA): K. Bryant; Affiliated PIs: S. Braithwaite, K. Crothers, D.A. Fiellin, M. Freiberg, V. LoRe; Participating VA Medical Centers: Atlanta (D. Rimland, J Guest), Baltimore (K.A. Oursler, R. Titanji), Bronx (S. Brown, S. Garrison), Houston (M. Rodriguez-Barradas, N. Masozera), Los Angeles (M. Goetz, D. Leaf), Manhattan-Brooklyn (M. Simberkoff, D. Blumenthal, H. Leaf, J. Leung), Pittsburgh (A. Butt, E. Hoffman), and Washington DC (C. Gibert, R. Peck); Core and Workgroup Chairs: C. Brandt, R. Dubrow, N. Gandhi, J. Lim, K. McGinnis, C. Parikh, J. Tate, E. Wang, J. Womack.
Steering Committee: A. Phillips (Chair), University College London (UCL), London; A. Babiker, MRC CTU, London; R. Brettle, The Lothian University Hospitals NHS Trust, Edinburgh; J. Darbyshire, MRC CTU, London; V. Delpech, Health Protection Agency, London; P. Easterbrook, King’s College Hospital, London; S. Fidler, St Mary’s Hospital, London; M. Fisher, Brighton & Sussex University Hospitals NHS Trust, Brighton; R. Gilson, West London Centre for Sexual Health, London; D. Goldberg, Health Protection Scotland, Glasgow; D. Hawkins, Chelsea & Westminster NHS Trust, London; H. Jaffe, University of Oxford, Oxford; A. Johnson, UCL, London; M. Johnson, UCL and Royal Free NHS Trust, London; K. McLean, West London Centre for Sexual Health, London; D. Pillay, UCL, London. Central co-ordination: Kholoud Porter (PI), Adam Cursley, Fiona Ewings, Keith Fairbrother, Louisa Gnatiuc, Sara Lodi, Brendan Murphy. Clinical centres and collaborators: G. Douglas, Aberdeen City Hospital, Aberdeen; N. Kennedy, Monklands Hospital, Airdrie; J. Pritchard, Ashford Hospital, Ashford; U. Andrady, Ysbyty Gwynedd, Bangor; N. Rajda, North Hampshire Hospital, Basingstoke; R. Maw, S. McKernan, Royal Victoria Hospital, Belfast; S. Drake, G. Gilleran, D. White, Birmingham Heartlands Hospital, Birmingham; J. Ross, Whittall Street Clinic, Birmingham; S. Toomer, Blackpool Victoria Hospital, Blackpool; R. Hewart, Royal Bolton Hospital, Bolton; H. Wilding, R. Woodward, Royal Bournemouth Hospital, Bourne-mouth; G. Dean, L. Heald, Royal Sussex County Hospital, Brighton; P. Horner, Bristol Royal Infirmary, Bristol; S. Glover, Southmead Hospital, Bristol; D. Bansaal, Queens Hospital, Burton-upon-Trent; S. Eduards, West Suffolk Hospital, Bury St Edmunds; C. Carne, Addenbrooke’s Hospital, Cambridge; M. Browing, R. Das, Cardiff Royal Infirmary, Cardiff; B. Stanley, North Cumbria Acute Hospitals NHS Trust, Carlisle; S. Estreich, A. Magdy, St Helier Hospital, Carshalton; C. O’Mahony, Countess of Chester Hospital, Chester; P. Fraser, Chesterfield & North Derbyshire Royal Hospital, Chesterfield; B. Hayman, St Richard’s Hospital, Chichester; S.P.R. Jebakumar, Essex County Hospital, Colchester; U. Joshi, Castle Hill Hospital, Cottingham; S. Ralph, Bishop Auckland General Hospital, County Durham; A. Wade, Coventry & Warwickshire Hospital, Coventry; R. Mette, Mayday University Hospital, Croydon; J. Lalik, Doncaster Royal Infirmary, Doncaster; H. Summerfield, Weymouth Community Hospital, Dorset; A. El-Dalil, Guest Hospital, Dudley; A.J. France, Dundee Royal Infirmary, Dundee; C. White, University Hospital of North Durham, Durham; R. Robertson, Muirhouse Medical Group, Edinburgh; S. Gordon, S. McMillan, S. Morris, Royal Infirmary of Edinburgh, Edinburgh; C. Lean, S. Morris, Western General Hospital, Edinburgh; K. Vithayathil, Leatherhead Hospital, Epsom; L. McLean, A. Winter, Gartnavel General Hospital & Glasgow Royal Infirmary, Glasgow; D. Gale, S. Jacobs, Gloucestershire Royal Hospital, Gloucester; Salford Hope Hospital, Greater Manchester; Farnham Road Hospital, Guildford; S. Tayal, Hartlepool University Hospital, Hartlepool; L. Short, Huddersfield Royal Infirmary, Huddersfield; Ayrshire Central Hospital, Irvine; M. Roberts, S. Green, Kidderminster General Hospital, Kidderminster; G. Williams, Crosshouse Hospital, Kilmarnock; K. Sivakumar, The Queen Elizabeth Hospital, King’s Lynn; D.N. Bhattacharyya, Victoria Hospital, Kirkaldy; E. Monteiro, Leeds General Infirmary, Leeds; J. Minton, St James Hospital, Leeds; J. Dhar, Leicester Royal Infirmary, Leicester; F. Nye, Royal Liverpool University Hospital, Liverpool; C.B. DeSouza, A. Isaksen, Barts & The London NHS Trust, London; L. McDonald, Central Middlesex Hospital, London; K. McLean, Charing Cross Hospital, London; A. Franca, D. Hawkins, Chelsea & Westminster Hospital, London; L. William, Ealing Hospital, London; I. Jendrulek, B. Peters, Guy’s & St Thomas NHS Trust, London; S. Shaunak, Hammersmith Hospital, London; S. El-Gadi, Homerton Hospital, London; P.J. Easterbrook, King’s College Hospital, London; C. Mazhude, Lewisham University Hospital, London; R. Gilson, R. Johnstone, Mortimer Market Centre, London; A. Fakoya, Newham General Hospital, London; J. Mchale, A. Waters, North Middlesex Hospital, London; S. Kegg, S. Mitchell, Queen Elizabeth Hospital Woolwich, London; P. Byrne, M. Johnson, Royal Free Hospital, London; P Rice, St George’s Hospital, London; S. Fidler, S.A. Mullaney, St Mary’s Hospital, London; S. McCormack, Victoria Sexual Health Clinic, London; D. David, West Middlesex University Hospital, London; R. Melville, Whipps Cross Hospital, London; K. Phillip, Whittington Hospital, London; T Balachandran, Luton & Dunstable Hospital, Luton; S Mabey-Puttock, A. Sukthankar, Manchester Royal Infirmary, Manchester; C. Murphy, E. Wilkins, North Manchester General Hospital, Manchester; S. Ahmad, Withington Hospital, Manchester; S. Tayal, James Cook Hospital, Middlesbrough; J. Haynes, Milton Keynes General Hospital, Milton Keynes; E. Evans, E. Ong, Newcastle General Hospital, Newcastle; R. Das, Royal Gwent Hospital, Newport; R. Grey, J. Meaden, Norfolk & Norwich University Hospital, Norwich; C. Bignell, City Hospital, Nottingham; D. Loay, K. Peacock, George Eliot Hospital, Nunneaton; M.R. Girgis, Royal Oldham Hospital, Oldham; B. Morgan, Radcliffe Infirmary, Oxford; A. Palfreeman, Peterborough District Hospital, Peterborough; J. Wilcox, Freedom Fields Hospital, Plymouth; J. Tobin, L. Tucker, St Mary’s Hospital, Portsmouth; A.M. Saeed, Royal Preston Hospital, Preston; F. Chen, Royal Berkshire Hospital, Reading; A. Deheragada, East Surrey Hospital, Redhill; O. Williams, Glan Clwyd District General, Rhyl; H. Lacey, Baillie Street Health Centre, Rochdale; S. Herman, D. Kinghorn, Royal Hallamshire Hospital, Sheffield; S. V. Devendra, J. Wither, Royal Shrewsbury Hospital, Shrewsbury; S. Dawson, Upton Hospital, Slough; D. Rowen, Royal South Hampshire Hospital, Southampton; J. Harvey, Stirling Royal Infirmary, Stirling; E. Wilkins, Stepping Hill Hospital, Stockport; A. Bridgwood, G. Singh, North Staffordshire Hospital, Stoke-on-Trent; M. Chauhan, Sunderland Royal Hospital, Sunderland; D. Kellock, S. Young, King’s Mill Centre, Sutton-in-Ashfield; S. Dannino, Y. Kathir, Singleton Hospital, Swansea; G. Rooney, The Great Western Hospital, Swindon; J. Currie, M. Fitzgerald, Taunton & Somerset Hospital, Taunton; S. Devendra, Princess Royal Hospital, Telford; F. Keane, Royal Cornwall Hospital, Truro; G. Booth, T. Green, Clayton Hospital, Wakefield; J. Arumainayyagam, S. Chandramani, Manor Hospital, Walsall; S. Rajamanoharan, T. Robinson, Watford General Hospital, Watford; E. Curless, Royal Albert Edward Infirmary, Wigan; R. Gokhale, Arrowe Park Hospital, Wirral; A. Tariq, New Cross Hospital, Wolverhampton; M. Roberts, Worcester Royal Infirmary, Worcester; O. Williams, Maelor Hospital, Wrexham; G. Luzzi, Wycombe General Hospital, Wycombe; M. FitzGerald, Yeovil District Hospital, Yeovil; I. Fairley, F. Wallis, Monkgate Health Centre, York Hospital NHS Trust, York. Laboratories: E. Smit, H.P.A. Birmingham; F. Ward, St Bartholomew’s and the Royal London NHS Trust.
J.M. Molina, B. Loze (St Louis – Paris), P. Morlat, M. Bonarek, F. Bonnet, C. Nouts, I. Louis (St André – Bordeaux), F. Raffi, V. Reliquet, F. Sauser, C. Biron, O. Mounoury, H. Hue, D. Brosseau (Hotel Dieu –Nantes), J.F. Delfraissy, C. Goujard, J. Ghosn, M.T. Rannou (Bicêtre – Le Kremlin Bicêtre), J.F. Bergmann, E. Badsi, A. Rami, M. Diemer, M. Parrinello (Lariboisière – Paris), P.M. Girard, D. Samanon-Bollens, P. Campa, M. Tourneur, N. Desplanques (St Antoine –Paris), J.M. Livrozet, F. Jeanblanc, P. Chiarello, D. Makhloufi (E. Herriot – Lyon), A.P. Blanc, T. Allègre (CHG – Aix en Provence), J. Reynes, V. Baillat, V. Lemoing, C. Merle de Boever, C. Tramoni (Gui de Chauliac – Montpellier), A. Cabié, G. Sobesky, S. Abel, V. Beaujolais (CHU – Fort de France), G. Pialoux, L. Slama, C. Chakvetadze, V. Berrebi (Tenon – Paris), P. Yeni, E. Bouvet, I. Fournier, J. Gerbe (Bichat – Paris), C. Trepo, K. Koffi, C. Augustin-Normand, P. Miailhes, V. Thoirain, C. Brochier (Hotel Dieu – Lyon), R. Thomas, F. Souala, M. Ratajczak (Pontchaillou – Rennes), J. Beytoux, C. Jacomet, F. Gourdon (G. Montpied –Clermont-Ferrand), E. Rouveix, S. Morelon, C. Dupont, C. Olivier (A. Paré – Boulogne), O. Lortholary, B. Dupont, J.P. Viard, A. Maignan (Necker – Paris), J.M. Ragnaud, I. Raymond (Pellegrin – Bordeaux), C. Leport, C. Jadand, C. Jestin, P. Longuet, S. Boucherit (Bichat – Paris), D. Sereni, C. Lascoux, F. Prevoteau (St Louis – Paris), A. Sobel, Y. Levy, J.D. Lelièvre, A.S. Lascaux, S. Dominguez, C. Dumont (H Mondor –Créteil), H. Aumaître, B. Delmas, M. Saada, M. Medus (St Jean – Perpignan), L. Guillevin, D. Salmon, T. Tahi (Cochin – Paris), Y. Yazdanpanah, S. Pavel, M.C. Marien (CH Dron – Tourcoing), B. Drenou, G. Beck-Wirth, C. Beck, M. Benomar (E Muller – Mulhouse), C. Katlama, R. Tubiana, H. Ait Mohand, A. Chermak, S. Ben Abdallah (Pitié-Salpétrière – Paris), M. Bentata, F. Touam, (Avicenne – Bobigny), B. Hoen, C. Drobacheff, A. Folzer (St Jacques – Besançon), P. Massip, M. Obadia, L. Prudhomme, E. Bonnet, F. Balzarin (Purpan –Toulouse), E. Pichard, J.M. Chennebault, P. Fialaire, J. Loison (CHR – Angers), P, Galanaud, F, Boué, D, Bornarel (Béclère – Clamart), R. Verdon, C. Bazin, M. Six, P. Ferret (CHR Côte de Nacre – Caen), L. Weiss, D. Batisse, G. Gonzales-Canali, D. Tisne-Dessus (HEGP –Paris), A. Devidas, P. Chevojon, I. Turpault (Corbeil Essonnes), A. Lafeuillade, A. Cheret, G. Philip (Chalucet – Toulon), P. Morel, J. Timsit (St Louis –Paris), S. Herson, N. Amirat, A. Simon, C. Brancion (Pitié-Salpétrière – Paris), J. Cabane, O. Picard, J. Tredup, N. Desplanques (St Antoine – Paris), A. Stein, I. Ravault (La Conception – Marseille), C. Chavanet, M. Buisson, S. Treuvetot (Bocage – Dijon), P. Choutet, P. Nau, F. Bastides (Bretonneau – Tours), T. May, L. Boyer, S. Wassoumbou (CHU – Nancy), E. Oksenhendeler, L. Gérard (St Louis – Paris), L. Bernard, P. De Truchis, H. Berthé (R Poincaré – Garches), Y. Domart, D. Merrien (CH – Compiègne), A. Greder Belan, (A Mignot – Le Chesnay), M. Gayraud, L. Bodard, A. Meudec (IMM Jourdan – Paris), C. Beuscart, C. Daniel, E. Pape (La Beauchée – St Brieuc), P. Vinceneux, A.M. Simonpoli, A. Zeng (L Mourier – Colombes), L. Fournier (M Jacquet – Melun), J.G. Fuzibet, C. Sohn, E. Rosenthal, M. Quaranta (L’Archet – Nice), P. Dellamonica, S. Chaillou, M. Sabah (L’Archet – Nice), B. Audhuy, A. Schieber (L Pasteur – Colmar), P. Moreau, M. Niault, O. Vaillant (Bretagne Sud – Lorient), G. Huchon, A. Compagnucci (Hotel-Dieu – Paris), I. De Lacroix Szmania, L. Richier (Intercommunal – Créteil), I. Lamaury (Abymes – Pointe à Pitre), F. Saint-Dizier, D. Garipuy (Ducuing – Toulouse), J.A. Gastaut, M.P. Drogoul, I. Poizot Martin, G. Fabre (St Marguerite –Marseille), G. Lambert de Cursay, B. Abraham, C. Perino (CH – Brives), P. Lagarde, F. David (CH – Lagny), J. Roche-Sicot, J.L. Saraux, A. Leprêtre (S Veil – Eaubonne), B. Fampin, A. Uludag, A.S. Morin (Beaujon – Clichy), O. Bletry, D. Zucman (Foch – Suresnes), A, Regnier (CH –Vichy), J.J. Girard (CH – Loches), D.T. Quinsat, L. Heripret (CH – Antibes), F. Grihon (Haute Vallée de l’Oise – Noyon), D, Houlbert (CH – Alençon), M. Ruel, K. Chemlal (CH – Nanterre), F. Caron, Y. Debab (C Nicolle – Rouen), F. Tremollieres, V. Perronne (F Quesnay – Mantes La Jolie), G, Lepeu, B, Slama (H Duffaut – Avignon), P. Perré (Les Oudairies – La Roche sur Yon), C. Miodovski (Paris), G. Guermonprez, A. Dulioust (CMC Bligny – Briis s/Forges), P. Boudon, D. Malbec (R Ballanger – Aulnay s/bois), O. Patey, C. Semaille (CH – Villeneuve St Georges), J. Deville, G. Remy, I. Béguinot (CH – Reims).
Hopital Antoine Beclere, Clamart (P. Galanaud, F. Boue, V. Chambrin, C. Pignon, G.A. Estocq, A. Levy), Hopital de Bicetre, Le Kremlin Bicetre (J.F. Delfraissy, C. Goujard, M. Duracinsky, P. Le Bras, M.S. Ngussan, D. Peretti, N. Medintzeff, T. Lambert, O. Segeral, P. Lezeau, Y. Laurian), Hopital Europeen Georges Pompidou, Paris (L. Weiss, M. Buisson, C. Piketty, M. Karmochkine, D. Batisse, M. Eliaszewitch, D. Jayle, D. Tisne- Dessus, M. Kazatchkine), Hopital Bichat Claude Bernard, Paris (C. Leport, U. Colasante, C. Jadand, C. Jestin, X. Duval, W. Nouaouia, S. Boucherit, J.L. Vilde), Hopital Saint Antoine, Paris (P.M. Girard, D. Bollens, D. Binet, B. Diallo, M.C. Meyohas, L. Fonquernie, J.L. Lagneau), Hopital Cochin, Paris (D. Salmon, L. Guillevin, T. Tahi, O. Launay, M.P. Pietrie, D. Sicard, N. Stieltjes, J. Michot), Hopital Henri Mondor, Creteil (A. Sobel, Y. Levy, F. Bourdillon, A.S. Lascaux, J.D. Lelievre, C. Dumont), Hopital Necker, Paris (B. Dupont, G. Obenga, J.P. Viard, A. Maignan), Hopital Paul Brousse, Villjuif (D. Vittecoq, L. Escaut, C. Bolliot), Hopital Pitie Salpetriere, Paris (F. Bricaire, C. Katlama, L. Schneider, S. Herson, A. Simon, M. Iguertsira), Hopital de la Conception, Marseille (A. Stein, C. Tomei, I. Ravaux, C. Dhiver, H. Tissot Dupont, A. Vallon, J. Gallais, H. Gallais), Hopital Sainte Marguerite, Marseille (J.A. Gastaut, M.P. Drogoul, G. Fabre), Hopital de L’Archet, Nice (P. Dellamonica, J. Durant, V. Mondain, I. Perbost, J.P. Cassuto, J.M. Karsenti, H. Venti, J.G. Fuzibet, E. Rosenthal, C. Ceppi, M. Quaranta), Hopital Avicenne, Bobigny (J.A. Krivitsky, M. Bentata, O. Bouchaud, P. Honore), Hopital Saint Louis, Paris (D. Sereni, C. Lascoux, J. Delgado), ACCTES/Hopital Necker, Paris (C. Rouzioux, M. Burgard, L. Boufassa), Hopital Mignot, Le Chesnay (J. Peynet).
Principal Investigator: Santiago Pérez Hoyos. Data analysis center: I Ferreros, I. Hurtado. Centro Nacional de Epidemiología: J. del Amo, I. Jarrín, C. González, A.M. Caro. Participating centres: Cohorte del Hospital Universitari Germans Trias I Pujol, Badalona (R. Muga, A. Sanviens, B. Clotet, J. Tor), Cohorte de Madrid-Sandoval (J. del Romero, P. Raposo, C. Rodríguez, S. García), Cohorte de los Centros de Atención y Prevención del SIDA, Barcelona (P. Garcia de Olalla, J. Cayla), Cohorte de los CIPS de la Comunidad Valenciana (I. Alastrue, J. Belda, P. Trullen, E. Fernández, C. Santos, T. Tasa, T. Zafra), Cohorte de las Prisiones de Cataluña (R. Guerrero, A. Marco), Cohorte de hemofílicos del Hospital La Paz, Madrid (M. Quintana), Cohortes de hemofílicos del Hospital Vall d?Hebron, Barcelona (I. Ruiz), Cohortes de hemofílicos del Hospital Virgen del Rocío, Sevilla (R. Nuñez, R Pérez), Cohorte de Navarra (J. Castilla, M. Guevara). Laboratory: C. de Mendoza, N. Zahonero.
Steering Committee: Antoniadou A., Chrysos G., Daikos G., Gargalianos-Kakolyris P., Gogos H.A., Katsarou O., Kordossis T., Lazanas M., Nikolaidis P., Panos G., Paparizos V., Paraskevis D., Sambatakou H., Skoutelis A., Touloumi G. (Chair). Coordinating Center: Department of Hygiene, Epidemiology and Medical Statistics, Athens University Medical School, Greece (Touloumi G., Pantazis N., Bakoyannis G., Gioukari V.) Participating Centers: 4th Dept of Internal Medicine, Athens Medical School, Attikon University Hospital (Antoniadou A., Papadopoulos A., Petrikkos G); Infectious Disease Unit, ’Tzaneio’ General Hospital of Pireaus (Chrysos G., Paraskeva D., Hatziastros P.); 1st Dept of Propedeutic Medicine, Athens University, Medical School ‘Laikon’ General Hopsital (Daikos G., Psichogiou M.); 1st Dept of Medicine, Infectious Diseases Unit, ‘G. Gennimatas’ Athens General Hospital (Gargalianos-Kakolyris P., Xylomenos G.); 1st Dept of Internal Medicine, Infectious Diseases Section, Patras University Hospital (Gogos HA, Maragos MN, Panos G); Haemophilia Centre, 2nd Blood Transfusion Centre, ‘Laikon’ Athens General Hospital (Katsarou O., Kouramba A., Ioannidou P.); AIDS Unit, Dept of Pathophysiology, ‘Laikon’ Athens General Hospital and Athens University, Medical School (Kordossis T., Kontos A.); Infectious Diseases Unit, Red Cross General Hospital of Athens (Lazanas M., Chini M., Tsogas N.); 1st Dept of Internal Medicine, Infectious Diseases Devision, AHEPA University Hospital, Aristotle University HIV Unit (Nikolaidis P., Kolaras P., Metallidis S.); 2nd Internal Medicine Clinic, 1st IKA (Panos G., Haratsis G.); AIDS Unit, Clinic of Venereologic & Dermatologic Diseases, Athens University, Medical School, Syngros Hospital (Paparizos V., Leuow K., Kourkounti S.); HIV Unit, 2nd Department of Internal Medicine, Athens University, Medical School, Hippokration General Hospital (Sambatakou H., Mariolis I.); Infectious Diseases & HIV Division, Dept of Internal Medicine, Evaggelismos Athens General Hospital (Skoutelis A., Papastamopoulos V., Baraboutis I.).
Conflicts of interest
The research was partly supported by NIH grants R01-AI073127, U10-AA013566, and MRC grant G0700820. VACS was supported by AHRQ grant R01-HS018372 and NIH grants U10-AA13566, U24-AA020794, U01-AA020790), R01-HL095136, R01-HL090342, RCI-HL100347, U01-A1069918 and P30-MH062294, and by the Veterans Health Administration Office of Research and Development (VA REA 08-266, VA IRR Merit Award) and Office of Academic Affiliations (Medical Informatics Fellowship). Jonathan Sterne has received travel grants from GlaxoSmithKline and honoraria from Gilead Sciences. Caroline Sabin has received travel grants, fees for speaking and honoraria from various pharmaceutical companies including Bristol Myers Squibb, Gilead Sciences, Boehringer-Ingelheim, Janssen Pharmaceutica, and Tibotec. Dominique Cost-agliola has received travel grants, consultancy fees, honoraria or study grants from various pharmaceutical companies including Abbott, Boehringer-Ingelheim, Bristol-Myers-Squibb, Gilead Sciences, GlaxoSmith-Kline, Janssen, Merck and Roche. Heiner C. Bucher has received travel grants, honoraria and unrestricted research grants from GlaxoSmithKline, Bristol-Myers-Squibb, Gilead, Roche, Abbott, Tibotec, Janssen, Boehringer-Ingelheim and ViiV Healthcare. Laurence Meyer has received honoraria from GlaxoSmithKline. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Sophie Abgrall has received travel grants, consultancy fees, fees for speaking from various pharmaceutical companies including Abbott, Boehringer-Ingelheim, Bristol-Myers-Squibb, Gilead Sciences, GlaxoSmithKline and Janssen.