The effect of combined antiretroviral therapy on the overall mortality of HIV-infected individuals : AIDS

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Epidemiology and Social

The effect of combined antiretroviral therapy on the overall mortality of HIV-infected individuals

 The HIV-CAUSAL Collaboration

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doi: 10.1097/QAD.0b013e3283324283
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The introduction of combined antiretroviral therapy (cART) in 1996 ushered in a new era for HIV-infected individuals in countries where this therapy was available. cART increases CD4 cell count, decreases HIV RNA level, and extends AIDS-free survival, at least in the short-term [1–5]. However, surrogate markers like CD4 cell count and HIV RNA are not fully adequate to infer the effect of cART on clinical endpoints [6–10]. In the current cART era, AIDS-free survival is less relevant than mortality alone because HIV-infected individuals often survive with acceptable quality of life following their first AIDS diagnosis and death is often the result of non-AIDS-defining causes [11]. Therefore, it would be highly desirable to have a reliable estimate of the effect of cART on the overall survival for public health planning and to inform HIV modeling and cost/effectiveness calculations.

Unfortunately, after 12 years of cART use in developed countries, the magnitude of the effect of cART on all-cause mortality remains unclear. The available effect estimates have been inferred from comparisons of mortality rates between the pre-cART era and the late-cART era [12–18]. These ecological comparisons may result in treatment misclassification (not all patients in the late-cART era take cART, and some pre-cART patients took monotherapy or dual therapy), may be confounded by temporal trends in healthcare quality, and do not appropriately adjust for important confounders like CD4 cell count and HIV RNA. Although a prospective cohort design can be used to mitigate, or eliminate, these problems, few cohort studies include sufficient antiretroviral-naive HIV-infected individuals to provide precise effect estimates of cART on all-cause mortality. Even fewer cohort studies can explore potential effect modification by key covariates such as CD4 cell count, HIV RNA viral load, transmission group, and sex.

Here, we present estimates of the effect of cART on all-cause mortality among HIV-1-infected individuals included in a large multinational collaboration of cohort studies from Europe and the United States. We also present these effect estimates stratified by clinical and demographic characteristics. Because unbiased estimation of the effect of cART requires appropriate adjustment for time-dependent confounding by indication (e.g., due to CD4 cell count and HIV RNA), we used inverse probability weighting of marginal structural models [19,20].


Study population

The HIV-CAUSAL Collaboration comprises 12 prospective cohort studies from five European countries and the United States. All cohorts in the collaboration are based on data collected for clinical purposes within national healthcare systems with essentially no barriers to access. The individual cohort studies are UK CHIC (United Kingdom) [21], ATHENA (the Netherlands) [22], FHDH-ANRS CO4 (France) [23], SHCS (Switzerland) [24], PISCIS (Spain) [25], CoRIS/CoRIS-MD [26,27] (Spain), VACS-VC (United States veterans) [28], UK Register of HIV Seroconverters [29] (United Kingdom), ANRS PRIMO (France) [30], ANRS SEROCO (France) [31], and GEMES (Spain) [15,32]. The last four studies include individuals for whom it was possible to estimate the time of HIV seroconversion (known as seroconverters). Individuals participating in both FHDH-ANRS CO4 and ANRS PRIMO/SEROCO were removed from FHDH-ANRS CO4, those in both CoRIS and PISCIS were removed from CoRIS, and those in UK CHIC and the UK Register of HIV Seroconverters were removed from UK CHIC. See Appendix for a description of each individual cohort.

The date of start of follow-up was cohort-specific and ranged from January 1996 to January 1998. Our analyses were restricted to HIV-1-infected individuals that met the following criteria at the start of follow-up: age 18 years or older, antiretroviral therapy-naive, no history of AIDS (defined as the onset of any Category C AIDS-defining illness [33]), no pregnancy (when information was available), HIV-RNA more than 500 copies/ml (in cohorts in which it could not be confirmed that the patient was therapy-naive), and CD4 cell count and HIV-RNA measurements within 6 months of each other. For each patient, follow-up ended at death, 12 months after the most recent laboratory measurement, pregnancy (if known), or the cohort-specific administrative end of follow-up (ranging between December 2003 and September 2007), whichever occurred earlier.

cART initiation was defined as the date at which a patient initiated treatment with either three or more antiretroviral drugs, or two ritonavir-boosted protease inhibitors, or one nonnucleoside reverse transcriptase inhibitor plus one boosted protease inhibitor. The date of death was identified independently by the cohorts using a combination of national and local mortality registries and clinical records (see Appendix for details).

Statistical methods

We fit a pooled logistic model [34] to estimate the average mortality hazard ratio for cART initiation versus noninitiation. The model included a time-varying indicator for ever use of cART, month of follow-up (restricted cubic splines with five knots) and the following baseline covariates: CD4 cell count (<100, 100 to <200, 200 to <350, 350 to <500, ≥500 cells/μl), HIV RNA level (<10 000, 10 000–100 000, >100 000 copies/ml), sex, transmission group (heterosexual, homosexual/bisexual, injection drug use, other or unknown), calendar year (1996–1998, 1999–2000, 2001–2006), age (<35, 35–50, >50 years), geographic origin (western developed countries, other or unknown), race (white, black, other or unknown), years since HIV diagnosis (<1 year, 1 to <5 years, >5 years, or unknown), and cohort. We fit a separate model with the cART indicator replaced by the variable ‘years since cART initiation’ (<1, 1 to <2, 2 to <3, 3 to <4, 4 to <5, and >5 years).

Because cART is more likely to be initiated in individuals with higher mortality risk (e.g., with low CD4 cell count and high HIV RNA levels), the estimates from the above regression model need to be adjusted for this time-dependent confounding by indication. To do so, one could add the time-varying confounders, CD4 cell count and HIV RNA, as covariates in the logistic regression model. However, this standard approach may introduce bias because the confounders are affected by prior cART use and are on the causal pathway between cART and mortality [35]. We, therefore, used inverse probability weighting to adjust for measured time-dependent confounders that are affected by prior cART use. Formally, under the assumption that all time-varying predictors of both cART and mortality were included in the analysis, our weighted model estimates the parameters of a marginal structural Cox model [19,36] and can be used to mimic a sequentially randomized trial in which patients were assigned to initiate cART at different times.

Each patient in the above logistic models received a time-varying weight inversely proportional to the estimated probability of having his/her own observed history of cART initiation, as described elsewhere [19,20]. To estimate each patient's probability of cART initiation in each month, we fit a pooled logistic model that included the covariates listed above for the mortality model plus the most recent measurement of the following time-varying covariates: CD4 cell count (restricted cubic splines with five knots), HIV RNA level (three categories), AIDS (yes, no), and time since last laboratory measure (five categories). To better adjust for cohort-specific factors, the weight models also included product terms between cohort and time of follow-up, time-varying CD4 cell count, and HIV RNA level. Inverse probability weights were also computed to adjust for potential selection bias due to censoring. Both the cART and censoring weights were stabilized as described elsewhere [19,20], and their product was used to fit the weighted regression model. To avoid undue influence of outliers on the variance of the estimates, we truncated the weights at a maximum value of 10. Truncation did not materially change the point estimates (nontruncated estimates not shown). The estimated weights used in the analysis had mean 1.05 (first percentile: 0.10; 99th percentile: 5.3). We computed 95% confidence intervals (CIs) by using variance estimators that take into account the procedure of weight estimation [36]. Subset analyses were performed according to the following baseline characteristics: sex, age, HIV RNA levels, CD4 cell count, transmission group, and baseline year.

Several sensitivity analyses were also performed: in addition to censoring individuals at 12 months without a laboratory measurement, we conducted separate analyses in which individuals were censored at 6, 18, and 24 months; the start of follow-up was delayed by 3 months; the weights were re-estimated by adding rate of CD4 cell count and HIV RNA change to the models; the weights were re-estimated by lagging the CD4 cell count and HIV RNA level 7 and 14 days to ensure that cART initiation was predicted using prior laboratory measurements; women starting cART with HIV RNA less than 500 were censored to reduce the probability that pregnant women were included in the analysis, individuals (mostly from the early-cART era) were censored if they did not start cART after having initiated some form of antiretroviral therapy; alternate definitions of cART were used; individuals were considered untreated during their first month on cART to allow for a lag period between cART initiation and its potential effect on mortality; and patients with AIDS at baseline were included in the analysis.

Because hazard ratios are not always simple to interpret and can be affected by selection bias, we also estimated absolute risks by cART status. To do so, we fit a weighted model that included linear and quadratic terms for the variable ‘years since cART initiation’. We then used the predicted values from this model to estimate the 5-year survival curves that would have been observed if all individuals had initiated cART at baseline and if no individuals had initiated cART during the follow-up period. All analyses were conducted with SAS 9.1.3 (SAS Institute Inc., Cary, North Carolina, USA).


Our study included 62 760 HIV-infected individuals who met the eligibility criteria. Of these, 26% initiated cART during the first 3 months and 55% during the entire follow-up. The average follow-up was 3.3 years. There were 2039 deaths during the follow-up, which yielded an overall mortality rate of 10 cases per 1000 person-years (Table 1). The mortality rate ranged from 6/1000 person-years in the seroconverters cohorts to 40/1000 person-years in the study of US veterans.

Table 1:
Characteristics of study participants and mortality hazard ratio for cART initiation versus non initiation, HIV-CAUSAL Collaboration.

The mortality hazard ratio for cART initiation versus no cART initiation ranged from 0.22 in the cohorts of seroconverters to 0.62 in the study of US veterans (P value for heterogeneity across cohorts was 0.21). The overall mortality hazard ratio (95% CI) was 0.48 (0.41–0.57) in the pooled dataset (Table 1), but this estimate varied by the individuals' baseline characteristics (Table 2). By CD4 cell count at baseline, the hazard ratio ranged from 0.29 (0.22–0.37) among those with less than 100 cells/μl to 0.77 (0.58–1.01) among those with 500 cells/μl or more. The mortality hazard ratio estimate also varied by time since cART initiation (Table 3). Compared with no cART initiation, the mortality hazard ratio ranged from 0.57 (0.49–0.67) for less than 1 year since cART initiation to 0.21 (0.14–0.31) for 5 or more years since cART initiation (P value for trend <0.001).

Table 2:
Mortality hazard ratio for cART initiation versus non initiation by baseline characteristics, HIV-CAUSAL Collaboration.
Table 3:
Mortality hazard ratio for cART initiation versus non initiation by time since initiation, HIV-CAUSAL Collaboration.

We also estimated the 5-year survival curves under cART initiation at baseline and under no cART initiation during the follow-up period. Overall, the estimated probability of surviving 5 years if cART had been initiated at baseline was 96%, compared with 92% if cART had not been initiated (Fig. 1). These estimates, however, varied by CD4 cell count at baseline (Fig. 2) and transmission group (Fig. 3). The 5-year survival for cART vs. no cART was 89 vs. 43% for CD4 cell count less than 100 cells/μl, 94 vs. 76% for 100 to less than 200 cells/μl, 97 vs. 91% for 200 to less than 350 cells/μl, 97 vs. 94% for 350 to less than 500 cells/μl, and 97 vs. 96% for 500 cells/μl or more. The 5-year survival for cART vs. no cART was 97 vs. 92% for heterosexuals, 97 vs. 95% for homo/bisexuals, 92 vs. 83% for injection drug users, and 95 vs. 94% for others.

Fig. 1:
Estimated survival curves under the regimes ‘initiate cART at baseline’ and ‘never start cART’, HIV-CAUSAL Collaboration.
Fig. 2:
Estimated survival curves under the regimes ‘initiate cART at baseline’ and ‘never start cART’ by CD4 cell count at baseline, HIV-CAUSAL Collaboration.
Fig. 3:
Estimated survival curves under the regimes ‘initiate cART at baseline’ and ‘never start cART’ by transmission group, HIV-CAUSAL Collaboration.

The sensitivity analyses described in the previous section did not materially change or suggest a weaker effect of cART (data not shown). For comparison purposes, we also fit unweighted models that did not include any covariates except cART initiation, included only baseline covariates, and included baseline and time-varying covariates. As expected, conventional adjustment via unweighted models led to hazard ratios closer to the null value (Fig. 4). The mortality hazard ratio for cART initiation vs. no initiation was 0.79 when no adjustment for time-varying confounding was attempted and 0.83 when conventional adjustment was used, versus 0.48 when inverse probability weighting was used.

Fig. 4:
Comparison between weighted and unweighted estimates of the mortality hazard ratio, HIV-CAUSAL Collaboration.


We estimated that initiation of cART reduced the overall incidence of mortality of HIV-infected individuals by 50%. In absolute terms, this mortality reduction was translated into a 5% increase in 5-year survival for cART initiation compared with no initiation. However, the absolute benefit depended on the baseline CD4 cell count: the survival increase ranged from about 46% in individuals with less than 100 cells/μl to about 1% in those with more than 500 cells/μl. Similarly, the absolute benefit was greatest in injection drug users compared with other transmission groups.

Because our collaboration includes a wide range of HIV-infected individuals living in Europe and the United States – including representative clinical cohorts, seroconverters, and US veterans – we could confirm that cART initiation was followed by 40–60% mortality reduction in all of these groups, with perhaps an even greater relative reduction among seroconverters. The survival benefit was clear even among US veterans, who experienced a higher mortality rate (40 deaths per 1000 person-years) than the other cohorts (6–13 deaths per 1000 person-years). The high mortality rate among US veterans – partly explained by their older age, predominantly male sex, and different death ascertainment procedures – is in line with those reported in similar populations [16,37,38].

Previous studies reported mortality hazard ratios for cART vs. no cART in the range 0.1–0.5. However, most previous studies on cART and mortality have been based on ecological comparisons and/or did not appropriately adjust for time-dependent confounders [12–18], which makes the estimates hard to interpret. Lack of appropriate adjustment for time-varying CD4 cell count and HIV RNA levels may result in either underestimation or overestimation of the effect of cART. In contrast to previous studies, we used a prospective cohort design and inverse probability weighting to appropriately adjust for measured confounders. It has been previously shown that effect estimates obtained from observational HIV cohorts via inverse probability weighting, but not those obtained via conventional adjustment methods, can replicate the findings of randomized clinical trials on cART and time to AIDS [3,20]. In the current analysis, we found empirical proof of the bias of conventional methods in that further adjustment for the strong time-varying confounding by indication resulted in a weaker (from 0.79 to 0.83), rather than stronger, effect estimate.

The validity of our effect estimates, however, relies on the untestable assumption that the measured covariates were sufficient to adjust for confounding by indication. We believe this assumption may approximately hold here because the most important clinical information used by physicians as indications for cART initiation (i.e., CD4 cell count and HIV RNA) was collected and used in the analysis. An incomplete or imperfect measurement of confounders would result in attenuation of the effect because the bias due to confounding by indication is upward in this setting. As a further protection against unmeasured confounding, we estimated the effect of cART initiation rather than the effect of continued cART use. This strategy makes it unnecessary to adjust for joint determinants of treatment discontinuation and death, which are less well measured in most observational studies. The price to pay for this strategy is again an attenuation of the effect estimate toward the null (as it would happen in the intention-to-treat analysis of a placebo-controlled randomized clinical trial) if a substantial proportion of individuals stopped taking cART during the follow-up. Thus, our effect estimates could be viewed as conservative estimates of the effect of continuous cART. Note, however, that the effect of continuous cART use would not be clinically interesting if most subjects who discontinue cART do so for toxicity-related reasons.

Other studies have used surrogate biological markers, like HIV RNA and CD4 cell count, in hopes of rapidly inferring the effect of cART on death. Several randomized studies, however, suggest that surrogate markers may not be good proxies for clinical endpoints like death [6–9]. In the MRC Delta Trial, CD4 cell count and HIV RNA changes overestimated clinical benefit (defined as survival or no disease progression) [9]. HIV RNA may be an inadequate surrogate for death because death may be caused mainly by immune system damage or unintended harmful effects via other mechanisms [39]; CD4 cell count may be inadequate due to biological and assay-based variability, differences between peripheral blood and lymphatic levels, and the existence of other important markers of immune function that are affected by treatment, like CD8 cells [9]. Even if surrogate biological markers provide some indication of short-term clinical endpoints, it is debatable whether these surrogate effects translate into long-term clinical effects, which depend on the interplay among immune factors, drug resistance, and toxicities that may not be evident in the short-term. For example, a regime might be perceived to be favorable in the short-term because its potency allows patients to maintain higher CD4 cell count and lower viral load, but over the long-term, this same potency might cause toxicities that lead to death more quickly. It is best to directly evaluate the effect of cART on mortality in large follow-up studies as we did here. An alternative would be to evaluate the effects of cART on cause-specific morbidity and mortality, but this information is not available in all HIV cohorts.

In summary, in the absence of data from long-term randomized clinical trials, appropriate adjustment for time-varying confounding in observational cohorts provide the best available evidence on the effects of cART on the overall mortality of HIV-infected individuals. We estimated that cART initiation halved the mortality rate of HIV-infected individuals in developed countries, and that the absolute reduction in mortality was stronger in those with worse prognosis at the start of follow-up. Thus, the 46% survival increase estimated for individuals who start cART at CD4 cell count less than 100 cells/μl demonstrates the benefits of being treated even at the most advanced stages of immunosupression. This finding, however, does not imply one should delay cART initiation until the CD4 cell count drops below 100 cells/μl because, besides the possibility of dying during the waiting period, the 5-year mortality risk of treated individuals with less than 100 cells/μl at baseline (11%) was almost four times greater than that of treated individuals with more than 500 cells/μl (3%).


Writing Committee: Maile Ray, Roger Logan, Jonathan A. C. Sterne, Sonia Hernández-Díaz, James M Robins (Coordinating Center), Caroline Sabin, Loveleen Bansi (UK CHIC), Ard van Sighem, Frank de Wolf (ATHENA), Dominique Costagliola, Emilie Lanoy (FHDH-ANRS CO4), Heiner C. Bucher, Viktor von Wyl (SHCS), Anna Esteve, Jordi Casabona (PISCIS), Julia del Amo, Santiago Moreno (CoRIS/CoRIS-MD), Amy Justice, Joseph Goulet (VACS), Sara Lodi, Andrew Phillips (UKRHS), Rémonie Seng, Laurence Meyer (PRIMO/SEROCO), Santiago Pérez-Hoyos, Patricia García de Olalla (GEMES), and Miguel A. Hernán (Coordinating Center).

This research was supported by NIH grants R01-AI073127 and T32-AI007358. Miguel Hernán, Principal Investigator of the HIV-CAUSAL Collaboration, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Jonathan Sterne has received travel grants from GlaxoSmithKline and honoraria from Gilead Sciences. Sonia Hernández-Díaz has received unrestricted training and research grants, or has consulted for Pfizer, Lilly, Wyeth, Novartis, and AstraZeneca. 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 Costagliola has received travel grants, consultancy fees, honoraria or study grants from various pharmaceutical companies including Abbott, Boehringer-Ingelheim, Bristol-Myers-Squibb, Gilead Sciences, GlaxoSmithKline, Janssen, Merck and Roche. Andrew Phillips has received reimbursement for either/or: attending a symposium; a fee for speaking; a fee for organising education; funds for research; funds for a member of staff; fees for consulting from various pharmaceutical companies including: Roche, BMS, GlaxoSmithKline, Abbott, Boehringer-Ingelheim, Gilead, Tibotec, Oxxon Therapeutics. Heiner C. Bucher has received travel grants, honoraria and unrestricted research grants from various pharmaceutical companies including, GlaxoSmithKline, Bristol-Myers-Squibb, Gilead, Roche, Abbott, Tibotec and Boehringer-Ingelheim. Laurence Meyer has received honoraria from GlaxoSmithKline.

Contributors to the HIV-CAUSAL Collaboration:

UK CHIC: Steering committee: AN Phillips, R Gilson, P Easterbrook, M Fisher, B Gazzard, M Johnson, J Walsh, C Leen, C Orkin, J Anderson, D Pillay, V Delpech, A Schwenk, D Dunn, M Gompels, T Hill, K Porter, A Babiker, C Sabin. Central co-ordination: Royal Free and University College, London (L Bansi, T Hill, A Phillips, C Sabin); Medical Research Council Clinical Trials Unit (MRC CTU), London (A Babiker, D Dunn, K Porter, S Sheehan).

Participating centres: King's College Hospital, London (P Easterbrook, A Waters, D Crates, S Mohamed-Saad); Brighton and Sussex University Hospitals NHS Trust (M Fisher, N Perry, A Pullin, D Churchill, W Harris); Chelsea and Westminster NHS Trust, London (B Gazzard, M Nelson, D Asboe, S Bulbeck, S Mandalia, J Clarke); Mortimer Market Centre, Royal Free and University College Medical School (RFUCMS), London (R Gilson, J Dodds, A Rider, I Williams); Health Protection Agency –Centre for Infections, London (V Delpech); Royal Free NHS Trust and RFUCMS, London (M Johnson, M Youle, F Lampe, C Smith, H Gumley, C Chaloner, D Ismajani Puradiredja); St. Mary's Hospital, London (J Walsh, J Weber, S Cashin, C Kemble, N Mackie, A Winston); Barts and The London NHS Trust, London (C Orkin, R Thomas, K Jones); Homerton Hospital, London (J Anderson, S Gann, K Jones); Edinburgh (C Leen, A Wilson); North Middlesex (A Schwenk, J Ainsworth); North Bristol NHS Trust (M Gompels).

ATHENA. Director: F de Wolf, HIV Monitoring Foundation, Amsterdam. Data analysis group: DO Bezemer, LAJ 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 (JM Prins*, JC Bos, JKM Eeftinck-Schattenkerk, SE Geerlings, MH Godfried, JMA Lange, JTM van der Meer, FJB Nellen, DP Olszyna, T van der Poll, P Reiss, SUC Sankatsing, R Steingrover, M van der Valk, JN Vermeulen, SME Vrouenraets, M van Vugt, FWMN Wit), Academic Hospital Maastricht, Maastricht (G Schreij*, S van der Geest, A Oude Lashof, S Lowe, A Verbon), Catharina Hospital, Eindhoven (B Bravenboer*, MJH Pronk), Emma Children's Hospital, Amsterdam (TW Kuijpers, D Pajkrt, HJ Scherpbier), Erasmus Medical Centre, Rotterdam (ME van der Ende*, H Bax, M van der Feltz, LBS Gelinck, JL Nouwen, BJA Rijnders, ED de Ruiter, L Slobbe, CAM Schurink, TEMS de Vries), Erasmus Medical Centre Sophia, Rotterdam (G Driessen, M van der Flier, NG Hartwig), Flevo Hospital, Almere (J Branger), Haga Hospital, location Leyenburg, Den Haag (RH Kauffmann*, EF Schippers), Kennemer Gasthuis, Haarlem (PHP Groeneveld*, MA Alleman, Isala Clinics, Zwolle; RW ten Kate*, R Soetekouw), Leiden University Medical Centre, Leiden (FP Kroon*, SM Arend, MGJ de Boer, PJ van den Broek, JT van Dissel, C van Nieuwkoop), Maasstadziekenhuis, location Clara, Rotterdam (JG den Hollander*), Medical Centre Alkmaar, Alkmaar (W Bronsveld*), Medical Centre Haaglanden, location Westeinde, Den Haag (R Vriesendorp*, FJF Jeurissen, EMS Leyten), Medical Centre Leeuwarden, Leeuwarden (D van Houte*, MB Polée), Medisch Spectrum Twente, Enschede (CHH ten Napel*, GJ Kootstra), Onze Lieve Vrouwe Gasthuis, Amsterdam (K Brinkman*, GEL van den Berk, WL Blok, PHJ Frissen, WEM Schouten), Medical Centre Jan van Goyen, Amsterdam (A van Eeden*, DWM Verhagen), Slotervaart Hospital, Amsterdam (JW Mulder*, ECM van Gorp, ATA Mairuhu, R Steingrover, J Wagenaar), St Elisabeth Hospital, Tilburg (JR Juttmann*, MEE van Kasteren), St Lucas Andreas Hospital, Amsterdam (J Veenstra*, WLE Vasmel), Radboud University Nijmegen Medical Centre, Nijmegen (PP Koopmans*, AM Brouwer, ASM Dofferhoff, R de Groot, HJM ter Hofstede, M Keuter, AJAM van der Ven), University Medical Centre Groningen, Groningen (HG Sprenger*, S van Assen, JTM van Leeuwen, CJ Stek), University Medical Centre Beatrix kliniek, Groningen (R Doedens, EH Scholvinck), University Medical Centre Utrecht, Utrecht (IM Hoepelman*, MME Schneider, MJM Bonten, PM Ellerbroek, CAJJ Jaspers, LJ Maarschalk-Ellerbroek, JJ Oosterheert, EJG Peters, T Mudrikova, MWM Wassenberg, S Weijer), Wilhelmina Children's Hospital, Utrecht (SPM Geelen, TFW Wolfs), Free University Medical Centre, Amsterdam (SA Danner*, MA van Agtmael, WFW Bierman, FAP Claessen, ME Hillebrand, EV de Jong, W Kortmann, RM Perenboom, EA bij de Vaate), Hospital Rijnstate, Arnhem (C Richter*, J van der Berg, EH Gisolf), Hospital Walcheren, Vlissingen (AA Tanis*), Hospitaal/Stichting Rode Kruis Bloedbank, Willemstad, Curaçao (AJ Duits, K Winkel, St Elisabeth).

FHDH-ANRS CO4: 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, MA Khuong, JM Lang, AS Lascaux, O Launay, A Mahamat, M Mary-Krause, S Matheron, JL Meynard, J Pavie, G Pialoux, F Pilorgé, I Poizot-Martin, C Pradier, J Reynes, E Rouveix, A Simon, P Tattevin, H Tissot-Dupont, JP 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 (JM Lacombe, V Potard). COREVIH: Paris area: Corevih Ile de France Centre (GH Pitié-Salpétrière: F Bricaire, S Herson, C Katlama, A Simon; Hôpital Saint-Antoine: N Desplanque, PM Girard, JL Meynard, MC Meyohas, O Picard; Hôpital Tenon: J Cadranel, C Mayaud, G Pialoux), Corevih Ile de France Est (Hôpital Saint-Louis: JP Clauvel, JM Decazes, L Gerard, JM Molina; GH 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, JL 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; GH Tarnier-Cochin: D Salmon; Hôpital Saint-Joseph: I Auperin, J Gilquin; Hôpital Necker adultes: L Roudière, JP Viard; Hôpital Antoine Béclère: F Boué, R Fior; Hôpital de Bicêtre: JF 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, JM Lang, D Rey; CH de Mulhouse: G Beck-Wirth), Corevih de l'Arc Alpin (CHU de Grenoble: JP Stahl, P Lecercq), Corevih Auvergne-Loire (CHU de Clermont-Ferrand: F Gourdon, H Laurichesse; CHRU de Saint-Etienne: A Fresard, F Lucht); Corevih Basse-Normandie (CHRU de Caen: C Bazin, R Verdon), Corevih Bourgogne (CHRU de Dijon: P Chavanet), Corevih Bretagne (CHU de Rennes: C Arvieux, C Michelet), Corevih Centre (CHRU de Tours: P Choutet, A Goudeau, MF Maître), Corevih Franche-Comté (CHRU de Besançon: B Hoen; CH de Belfort: P Eglinger, JP Faller); Corevih Haute-Normandie (CHRU de Rouen: F Borsa-Lebas, F Caron), Corevih Languedoc-Roussillon (CHU de Montpellier: J Reynes; CHG de Nîmes: JP Daures), Corevih Lorraine (Nancy Hôpital de Brabois: T May, C Rabaud; CHRU de Reims: JL Berger, G Rémy), Corevih de Midi-Pyrénées (Toulouse CHU Purpan: E Arlet-Suau, L Cuzin, P Massip, MF Thiercelin Legrand; Toulouse Hôpital la Grave: G Pontonnier; Toulouse CHU Rangueil), Corevih Nord-Pas de Calais (CH de Tourcoing: N Viget, Y Yasdanpanah), Corevih PACA Est (Nice Hôpital Archet 1: P Dellamonica, C Pradier, P Pugliese; CHG Antibes-Juan les Pins: K Aleksandrowicz, D Quinsat), Corevih PACA Ouest (Marseille Hôpital de la Conception: I Ravaux, H Tissot-Dupont; Marseille Hôpital Nord: JP Delmont, J Moreau; Marseille Institut Paoli Calmettes: JA Gastaut; Marseille Hôpital Sainte-Marguerite: I Poizot-Martin, F Retornaz, J Soubeyrand; Marseille Centre pénitentiaire des Baumettes: A Galinier, JM Ruiz; CHG d'Aix-En-Provence: T Allegre, PA Blanc; CH d'Arles: D Bonnet-Montchardon; CH d'Avignon: G Lepeu; CH de Digne Les Bains: P Granet-Brunello; CH de Gap: JP Esterni, L Pelissier; CH de Martigues: R Cohen-Valensi, M Nezri; CHI de Toulon: S Chadapaud, A Laffeuillade), Corevih Pays de la Loire (CHRU 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: JM Livrozet, JL Touraine; Lyon Hôtel-Dieu: L Cotte, C Trepo). Overseas: Corevih Guadeloupe (CHRU de Pointe-à-Pitre: M Strobel; CH Saint-Martin: F Bissuel), Corevih Guyane (CHG de Cayenne: R Pradinaud, M Sobesky), Corevih Martinique (CHRU de Fort-de-France: A Cabié), Corevih de La Réunion (CHD Félix Guyon: C Gaud, M Contant).

Swiss HIV Cohort Study (SHCS): C Aebi, M Battegay, E Bernasconi, J Böni, P Brazzola, HC 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), HJ 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.

PISCIS: Coordinators: J Casabona (Centre d'Estudis Epidemiològics les Infeccions de Transmissió Sexual i Sida de Catalunya: CEEISCAT), JM Miró (Hospital Clínic-Idibaps, Universitat de Barcelona). Field coordinator: A Alquézar, V Isern (CEEISCAT). Steering committee: J Casabona, A Esteve, A Alquézar (CEEISCAT), JM Miró (Hospital Clínic-Idibaps, Universitat de Barcelona), D Podzamczer (Hospital de Bellvitge de Barcelona), J Murillas (Hospital Son Dureta de Mallorca). Scientific committee: JM Gatell, F Agüero (Hospital Clínic-Idibaps, Universitat de Barcelona), C Tural, B Clotet (Hospital Universitari Germans Trias i Pujol, Universitat Autónoma de Barcelona), E Ferrer (Hospital de Bellvitge de Barcelona), M Riera (Hospital Son Dureta de Mallorca) F Segura G Navarro (Corporació Parc Taulí de Sabadell), L Force (Hospital de Mataró), J Vilaró (Hospital de Vic), A Masabeu (Hospital de Palamós), I García (Hospital General d'Hospitalet), M Guadarrama (Hospital Alt Penedès de Vilafranca), A Romero, C Agustí (CEEISCAT). Data Management and statistical analysis: A Esteve, A Montoliu, N Ortega (CEEISCAT), E Lazzari (Hospital Clínic- Idibaps, Universitat de Barcelona). Technical support: E Puchol (CEEISCAT), M Sanchez (Hospital Clínic- Idibaps, Universitat de Barcelona). Participating centres: Hospital Clínic-Idibaps, Barcelona (JL Blanco, F Garcia-Alcaide, E Martínez, J Mallolas M López-Dieguez, JF García-Goez), Hospital Universitari Germans Trias i Pujol, Barcelona (G Sirera, J Romeu, A Jou, E Negredo, C Miranda, MC Capitan), Hospital Universitari de Bellvitge, L'Hospitalet (M Olmo, P Barragan, M Saumoy, F Bolao, C Cabellos, C Peña), Corporació Sanitària Parc Taulí (M Sala, M Cervantes, MJ Amengual, M Navarro, E Penelo), Hospital de Mataró (P Barrufet), Hospital Alt Penedès de Vilafranca (M Guadarrama).

CORIS/CORIS-MD: Steering committee: J Berenguer, J del Amo, F García, F Gutiérrez, P Labarga, S Moreno, MA Muñoz. Field work, data management, and statistical analyses: AM Caro-Murillo, P Sobrino, I Jarrín. Participating centres: Hospital Universitario de Canarias, Santa Cruz de Tenerife (JL Gómez Sirvent, P Rodríguez, MR Alemán, MM Alonso, AM López, MI Hernández), Hospital Carlos III, Madrid (V Soriano, P Labarga, P Barreiro, J Medrano, P Rivas, D Herrero, F Blanco, ME 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 (JA Iribarren, J Arrizabalaga, MJ Aramburu, X Camino, F Rodríguez-Arrondo, MA von Wichmann, L Pascual, MA Goenaga), Hospital General Universitario de Elche (F Gutiérrez, M Masiá, JM Ramos, S Padilla, V Sánchez-Hellín, E Bernal, C Escolano, F Montolio, Y Peral), Hospital Gregorio Marañón, Madrid (J Berenguer, JC 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 (JL 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 (JA Oteo, JR Blanco, V Ibarra, L Metola, M Sanz, L Pérez-Martínez), Hospital de Navarra, Pamplona (J Sola, J Uriz, J Castiello, J Reparaz, MJ Arriaza, C Irigoyen), Hospital Ramón y Cajal, Madrid (S Moreno, A Antela, JL Casado, F Dronda, A Moreno, MJ 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, LF López-Cortés, M Trastoy, R Mata).

Veterans Aging Cohort Study-Virtual Cohort: Principal investigator and co-principal investigator: AC Justice, DA Fiellin. Participating VA centers: Atlanta, GA (D. Rimland, C Jones-Taylor), Baltimore, MD (KA Oursler, R Titanji), Bronx, NY (S Brown, S Garrison), Houston, TX (M Rodriguez-Barradas, N Masozera), Los Angeles, CA (M Goetz, D Leaf), Manhattan-Brooklyn, NY (M Simberkoff, D Blumenthal, J Leung), Pittsburgh, PA (A Butt, E Hoffman), and Washington, DC (C Gibert, R Peck). Core Faculty: K Mattocks (Deputy Director), S Braithwaite, C Brandt, K Bryant, R Cook, J Conigliaro, K Crothers, J Chang, S Crystal, N Day, J Erdos, M Freiberg, M Kozal, N Gandhi, M Gaziano, M Gerschenson, B Good, A Gordon, JL Goulet, MA Hernán, K Kraemer, J Lim, S Maisto, P Miller, L Mole, P O'Connor, R Papas, JM Robins, C Rinaldo, M Roberts, J Samet, B Tierney, J Whittle.

UK Register of HIV Seroconverters: 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, Bournemouth; 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; SPR 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; CB 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; PJ 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, SA 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; MR 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; AM 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, HPA Birmingham; F Ward, St Bartholomew's and the Royal London NHS Trust.

PRIMO: JM 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), JF Delfraissy, C Goujard, J Ghosn, MT Rannou (Bicêtre – Le Kremlin Bicêtre), JF Bergmann, E Badsi, A Rami, M Diemer, MParrinello (Lariboisière - Paris), PM Girard, D Samanon-Bollens, P Campa, M Tourneur, N Desplanques (St Antoine - Paris), JM Livrozet, F Jeanblanc, P Chiarello, D Makhloufi (E Herriot - Lyon), AP 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, JP Viard, A Maignan (Necker - Paris), JM 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, JD Lelièvre, AS 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, MC 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, JM 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, AM Simonpoli, A Zeng (L Mourier - Colombes), L Fournier (M Jacquet - Melun), JG 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), JA Gastaut, MP 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, JL Saraux, A Leprêtre (S Veil - Eaubonne), B Fampin, A Uludag, AS Morin (Beaujon – Clichy), O Bletry, D Zucman (Foch - Suresnes), A Regnier (CH - Vichy), JJ Girard (CH - Loches), DT 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).

SEROCO: Hopital Antoine Beclere, Clamart (P Galanaud, F Boue, V Chambrin, C Pignon, GA Estocq, A Levy), Hopital de Bicetre, Le Kremlin Bicetre (JF Delfraissy, C Goujard, M Duracinsky, P Le Bras, MS 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, JL Vilde), Hopital Saint Antoine, Paris (PM Girard, D Bollens, D Binet, B Diallo, MC Meyohas, L Fonquernie, JL Lagneau), Hopital Cochin, Paris (D Salmon, LGuillevin, T Tahi, O Launay, MP Pietrie, D Sicard, N Stieltjes, J Michot), Hopital Henri Mondor, Creteil (A Sobel, Y Levy, F Bourdillon, AS Lascaux, JD Lelievre, C Dumont), Hopital Necker, Paris (B Dupont, G Obenga, JP 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 (JA Gastaut, MP Drogoul, G Fabre), Hopital de L'Archet, Nice (P Dellamonica, J Durant, V Mondain, I Perbost, JP Cassuto, JM Karsenti, H Venti, JG Fuzibet, E Rosenthal, C Ceppi, M Quaranta), Hopital Avicenne, Bobigny (JA 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).

GEMES: Principal Investigator: S Pérez Hoyos. Data analysis center: I Ferreros, I Hurtado. Centro Nacional de Epidemiología: J del Amo, I Jarrín, C González, AM Caro. Participating centres: Cohorte del Hospital Germans Trias I Pujol, Badalona (R Muga, A Sanvicens, 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.


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Description of cohort studies participating in the HIV-CAUSAL Collaboration.

The UK Collaborative HIV Cohort Study (UK CHIC) [21] includes HIV-infected individuals from 10 large outpatient HIV clinical centers in the UK. Clinical records data were entered into electronic databases by each center with data prospectively from 1996; these databases were pooled in 2001 and at yearly intervals subsequently. Quality control is conducted through multiple data checks and resolution of discrepancies via queries. Individuals are followed-up at the time of their clinic appointments. Death is ascertained with outpatient medical records and anonymous linkage to UK death registries.

The ATHENA Cohort Study (AIDS Therapy Evaluation National AIDS Therapy Evaluation Centre) [22] includes HIV-infected individuals presenting at any of 24 hospitals and four pediatric HIV treatment centers in the Netherlands since 1998. Clinical records data are collected by trained staff in each participating hospital, and quality control is performed by source data verification. Individuals are followed-up at the time of their clinic appointments. Mortality is reported by a hospital physician and an HIV Monitoring Foundation data monitor.

The French Hospital Database on HIV (FHDH ANRS CO4) [23] includes HIV-positive individuals seen at 68 French teaching hospitals belonging to 29 HIV Treatment and Information Centres (COREVIH) in mainland France and French overseas territories. Data have been collected since 1992 through medical records and structured questionnaires with trained research assistants. Quality control is performed via monitored on-site source documentation (AUDIT on randomized individuals). Individuals are followed-up at the time of their clinic appointments, usually every 3 to 4 months, and the study attempts to collect information at least every 6 months. Death is ascertained through medical records review.

The Swiss HIV Cohort Study (SHCS) [24] includes individuals presenting at any of seven outpatient clinics in Switzerland. Data have been prospectively collected via clinical records with standardized criteria since 1988. Individuals are followed-up at the time of their clinic appointments, usually every 3 to 4 months, and the study attempts to collect information at least every 6 months. Death is ascertained by physician report, and survival status is verified with physicians biannually for patients with no new data in the preceding14 months.

The PISCIS Cohort Study [25] includes HIV-positive, therapy-naive patients who present at any of 10 participating hospitals in Catalonia and the Balearic Islands, Spain, since 1998. Data are collected via computerized clinical records. Data quality is tested with quality control reports and site visits. The cohort strives for follow-up every 3 to 6 months. Death is ascertained through clinic records, active follow-up, and linkage to vital statistics agencies.

CoRIS [26] includes HIV-infected, therapy-naive adults from 19 hospitals from nine of the 17 Autonomous Communities of Spain linked to a Biobank. Recruitment started January 1, 2004 and is on-going. Quality control is conducted via internal and external quality controls, with 10% of cohort members submitted to an external audit. Patients are followed-up at the time of their clinic appointments, usually every 3 to 4 months. Mortality records are cross-checked with the National Death Index to validate causes of death. CoRIS-MD [27] is an open cohort study of HIV-infected subjects with at least 6 months of follow-up in any of 10 hospitals from seven of the 17 Autonomous Communities of the country between 1997 and 2003. The cohort was assembled in 2004. Patients were followed-up at the time of their routine clinical appointments, usually every 3 to 4 months, until December 2003. All patients were crossed-checked with the National Death Index to ascertain mortality and to validate causes of death.

The Veterans Aging Cohort Study Virtual Cohort (VACS-VC) [28] includes HIV-infected subjects identified through the U.S. Veterans Administration electronic medical records since 1997. To be eligible, patients need at least two outpatient codes or one inpatient code according to an algorithm to identify HIV-infected subjects from clinical records. Patients in VACS-VC are seen according to usual care guidelines, on average once every 4 months. Deaths are ascertained quarterly via searches in the Beneficiary Identification Records Locator Subsystem (BIRLS) and inpatient files in the electronic medical records system. This ascertainment method was found comparable to that obtained from the National Death Index.

Seroconverter Cohorts: The UK Register of Seroconverters [29] includes HIV-infected individuals presenting at any of 121 clinical centers in the UK whose time of seroconversion is known with reasonable precision. Data have been collected prospectively since 1994 (retrospectively to 1984) through annual clinical report forms. Death is ascertained through clinical records and biannual linkage to national death registries (the Office of National Statistics and the General Register Officer).

The ANRS PRIMO Cohort Study [30] includes individuals presenting with primary HIV infection in any of 80 French hospitals since 1996. The participants' time of seroconversion is confirmed through laboratory testing with reasonable precision. Data are collected through medical records, laboratory measurement, autoquestionnaires, and frozen serum, plasma, and cells. The cohort attempts to follow up with individuals every 6 months. Death is identified through medical records and cross-checked with city hall records.

The ANRS SEROCO Cohort Study [31] includes individuals presenting with recent HIV diagnosis (<1 year) or a known date of infection in any of 18 participating clinical sites in France. The cohort was established in 1988, and data are collected from medical records and frozen laboratory samples. The scheduled interval of follow-up is every 6 months. Death is ascertained via medical records and biennial cross-check with the National Register of Deaths.

The Spanish Multicenter Study Group of Seroconverters (GEMES) [32] includes individuals from 10 seroconverter cohorts in Spain. These cohorts are drawn from hospitals, STI clinics, and counseling and testing centers. For members of all participating cohorts, the time of seroconversion is confirmed via laboratory testing. The study was assembled in 1998 but includes people who seroconverted from 1982 retrospectively. Data from participants are updated yearly from clinical records and cross-checked with AIDS and mortality registries.


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antiretroviral therapy; HIV infection; inverse probability weighting; marginal structural models; mortality

© 2010 Lippincott Williams & Wilkins, Inc.