Introduction
Sustained viral suppression and immune recovery during combined antiretroviral therapy (cART) leads to a reduction in HIV-1-related morbidity and mortality [1,2]. However, by comparison with the general uninfected population, overall mortality on cART continues to be higher among some specific HIV groups [3–5]. Despite experiencing more AIDS-defining events during the first year of cART [6], migrants from sub-Saharan Africa (SSA) seem to have lower mortality than nonmigrants, mainly owing to lower non-AIDS mortality [7,8], although it is noteworthy that injecting drug users were overrepresented among nonmigrants [6–8].
Apart from the hypothesis of a healthy migrant effect, cohort studies have given conflicting results for immunovirological outcomes on cART. For example, poorer virological responses [9–11] and immunological responses [9,12] have been observed among SSA migrants than among nonmigrants in several European countries. In France, a cross-sectional study showed a higher risk of both immunovirological and clinical cART failure among heterosexual migrants (mainly from SSA) than among MSM [13], whereas another cohort study showed no differences between these two groups [14]. When considering sex, results are also conflicting, with better immunovirological responses [12,15] and clinical responses [15,16] on cART reported in women compared with men in some studies, but worse clinical outcomes in women [17] or no differences in other studies [9,18,19].
In a cohort of HIV-infected individuals followed in France from 2006 to 2012, we compared virological, immunological, and clinical outcomes after first-line cART initiation between HIV-1-infected migrants originating from SSA or non-French West Indies (NFW) and French natives (FRA), according to sex and the HIV transmission group. Because morbidity and mortality are increasingly attributed to non-AIDS events [20–22], the studied negative clinical outcomes included new AIDS-defining events and AIDS-related death, and also serious non-AIDS-defining events and AIDS-unrelated death.
Methods
Individuals
Created in 1989, the French Hospital Database on HIV (FHDH) is a large prospective cohort study of HIV-infected individuals receiving care in one of the 70 French participating hospitals [23]. We considered for this study all ART-naïve HIV-1-infected individuals aged at least 16 years and originating from FRA, SSA or NFW, enrolled in the FHDH cohort and who started cART between 01 January 2006 and 31 December 2011. Individuals were excluded if their first cART regimen was prescribed for pregnancy. At treatment initiation, at least 1 year prior to the last database update, patients had to have at least one available CD4+ cell count and one plasma viral load (pVL) measurement obtained within the previous 6 months. Only individuals with at least one available CD4+ cell count and one pVL measurement following cART initiation were included in the study (Fig. 1).
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Fig. 1: Flow chart. *cART regimens defined as at least three drugs or two drugs from among ritonavir-boosted protease inhibitor, nonnucleoside reverse transcriptase inhibitor and integrase inhibitor, or ritonavir-boosted protease inhibitor monotherapy.cART, combination antiretroviral therapy; FRA, French natives; NFW, non-French West Indies; SSA, sub-Saharan Africa.
Statistical analysis
Migrant status was based on the United Nations definition: ‘anyone born and having lived outside France and now residing in France, whatever their nationality and the duration of stay in France’ [24]. Regions of geographic origin were subdivided in two groups as follows: FRA, including the French West Indies, and SSA/NFW pooled on the basis of their similar proportion of undocumented migrants. Individuals from other countries were excluded because of the small numbers in each region (North Africa n = 220, America n = 203, Asia/Middle East n = 108, and Europe n = 204).
The χ2 and Mann–Whitney U tests were used to compare demographic, immunovirological, and therapeutic characteristics at cART initiation, across the two regions of origin. To further explore differences related to geographic origin, sex, and HIV transmission group, a combined five-category variable was created: MSM originating from FRA (FRA MSM), nonhomosexual men originating from FRA, women originating from FRA, men originating from SSA/NFW, and women originating from SSA/NFW.
We studied the following endpoints after first-line cART initiation: time to undetectable pVL (date of the second of two consecutive values < 50 copies/ml); time to CD4+ cell recovery (date of the second of two consecutive values > 500/μl); time to a new AIDS-defining event or AIDS-related death [25]; time to a serious non-AIDS event (SNAE) or AIDS-unrelated death; and time to a new AIDS-defining event, SNAE, or death. As proposed by others [26,27], SNAE consisted of unscheduled overnight hospitalization or any of the following events: cardiovascular event (myocardial infarction, stroke, or coronary revascularization), peripheral arterial disease, deep vein thrombosis or pulmonary embolism, end-stage renal disease (dialysis or renal transplantation), decompensated liver disease, complicated diabetes mellitus, severe bacterial, fungal, viral or parasitic infection, and non-AIDS-defining cancer. Any death not attributable to AIDS was considered to be an AIDS-unrelated death after verification that the recent medical history of the patient in the database – high CD4+ cell count, no cART interruption, no AIDS event in the previous year – did not support the hypothesis of an AIDS death.
Cox proportional hazard models were used to identify differences in biological outcomes according to geographic origin, sex, and HIV transmission group. Patients who started cART with a CD4+ cell count at least 500/μl were excluded from the immunological analysis, the endpoint being the recovery of more than 500 CD4+ cells/μl. Cumulative incidence curves and regression analyses taking into account loss to follow-up as a competing risk, providing subdistribution hazard ratios (SHRs) [28], were used to identify differences in clinical outcomes according to geographic origin, sex, and HIV transmission group. Loss to follow-up was defined as an interval of more than 18 months between the last follow-up visit and the last database update. Individuals not experiencing the event were censored at the end of follow-up, 31 December 2012, or death in all analyses, 2 years after cART initiation for biological analyses, or 5 years after cART initiation for clinical analyses, whichever occurred first. A 2-year follow-up period after first-line cART initiation was chosen for biological outcomes, because of the 96-week follow-up period required for new drug marketing approval in Europe and the United States. Total 5 years of follow-up after first-line cART initiation was chosen for the clinical outcomes, because non-AIDS clinical events secondary to prolonged immunodeficiency, a low CD4+ cell nadir or slow immune recovery on cART can occur late after virological success and immune recovery.
To evaluate the influence of geographic origin, sex, and HIV transmission group, multivariable models were adjusted for baseline variables: age, the calendar period of first-line cART initiation, the region of care, the CD4+ cell count (log2) and pVL (log10) at cART initiation as continuous variables, preexisting AIDS status, hepatitis B virus antigen and antihepatitis C virus antibody status, first-line cART initiation during the primary infection, time since HIV diagnosis, and the type of first-line cART for all analyses. Then, to assess if the observed differences between the demographic groups were explained by response to cART, we subsequently also adjusted for time-dependent pVL undetectability in immunological analyses, and time-dependent pVL undetectability and time-dependent CD4+ cell count increment of more than 50/μl after cART initiation in all clinical analyses. Regions of care were defined according to the epidemiology of HIV infection in France, and comprised the Paris area, southeast France (Provence-Alpes-Côte d’Azur), the French West Indies (Martinique, Guadeloupe, French Guyana), and other regions of metropolitan France plus Reunion Island [29]. The two periods of first-line cART initiation (2006–2007 and 2008–2011) were chosen according to the evolution of national and international cART guidelines [30–32]. Because it is better to impute missing data than to ignore them [33], we created five datasets in which missing data on variables relating to hepatitis B (n = 1949, 20%) and C (n = 1881, 19.3%) were imputed from the patient's other covariables. In these imputations, missing values were randomly sampled from their predicted distributions [34]. Analyses were run on each of the five datasets, including the imputed values, and the results were combined with Rubin's rules [34].
An intent-to-continue-treatment approach was used for all analyses, and we thus ignored subsequent treatment modifications, including treatment interruptions. We also did a sensitivity analysis using an alternative immunological outcome, namely recovery of at least 50 CD4+ cells/μl within 6 months after cART initiation and at least 100 CD4+ cells/μl within 1 year after cART initiation. We also used a different definition for loss to follow-up, consisting of all interruptions of follow-up lasting more than 18 months. All analyses were done with SAS v9.4 software (SAS Institute, Inc., Cary, North Carolina, USA). A P value less than 0.05 was considered to denote statistical significance.
Results
Population
A total of 9746 individuals were included in the study, of whom 7297 (74.9%) were FRA and 2449 (25.1%) were from SSA/NFW (Table 1). In the latter group, 2186 individuals (89.3%) originated from SSA and 263 (10.7%) from NFW (mainly Haiti: 82.1%). The SSA and NFW migrants were similar with respect to the HIV transmission groups, CD4+ cell counts and pVL values at cART initiation, first-line cART initiation during the primary infection, and the category of cART. By comparison with NFW migrants, SSA migrants comprised more women and fewer individuals with preexisting AIDS status, and tended to start cART during the more recent period (data not shown). MSM composed 38.8% of the study population and most originated from FRA (98.3%). Fewer individuals from FRA (n = 2004, 27.5%) than SSA/NFW migrants (n = 934, 38.1%) initiated cART with a CD4+ cell count below 200/μl.
Table 1: Characteristics of the population at first-line cART initiation, according to geographic origin (France, 2006–2011, n = 9746).
Virological response
Overall, the 2-year Kaplan–Meier probability of pVL undetectability after cART initiation was 83.2% [95% confidence interval (CI), 82.9–83.4]. The lowest estimated probabilities were for FRA nonhomosexual men and SSA/NFW men (Fig. 2a). Compared with FRA MSM, the hazard ratios for pVL undetectability were 0.84 (95% CI, 0.78–0.89) in FRA nonhomosexual men, 0.93 (95% CI, 0.87–0.99) in FRA women and 0.87 (95% CI, 0.80–0.94) in SSA/NFW men, after adjustment. No significant difference was observed between FRA MSM and SSA/NFW women. Compared with FRA MSM, all women, whatever their geographic origin, had no significant difference in time to viral undetectability [adjusted hazard ratio (aHR), 0.99 (95% CI, 0.93–1.05)], whereas all nonhomosexual men whatever their geographic origin had a significant lower likelihood of undetectability [aHR, 0.85 (95% CI, 0.80–0.90), P < 0.0001]. Results were similar when NFW individuals were excluded from the analyses (data not shown).
Fig. 2: Crude and adjusted hazard ratios for undetectable pVL (n = 9746) (a) and CD4+ cell recovery (n = 8856) (b) after first-line cART initiation, according to geographic origin, sex and HIV transmission group (Cox models, France, 2006–2012).Virological analysis (a): HR adjusted for characteristics at cART initiation immunological analysis (b): model 1: HR adjusted for characteristics at cART initiation. model 2: model 1 + undetectable pVL as a time-dependent variable. cART, combination antiretroviral therapy; FRA, French natives; HR, hazard ratio; NFW, non-French West Indies; pVL, plasma viral load; SSA, sub-Saharan Africa.
Immunological response
The immunological response was assessed in 8856 individuals with CD4+ cell counts less than 500/μl at cART initiation. Overall, the 2-year Kaplan–Meier probability of CD4+ cell recovery more than 500/μl after cART initiation was 40.0% (95% CI, 39.5–40.5), ranging from 28.2% (95% CI, 26.9–29.5) in SSA/NFW men to 50.9% (95% CI, 49.4–52.4) in FRA MSM (Fig. 2b). Crude hazard ratios for CD4+ cell recovery were lower in all groups compared with FRA MSM. After adjustment for characteristics at cART initiation, the likelihood of CD4+ cell recovery was lower in all groups than in FRA MSM, and was lowest in migrants [aHR, 0.65 (95% CI, 0.56–0.75) for SSA/NFW men and 0.72 (95% CI, 0.64–0.81) for SSA/NFW women; and aHR, 0.90 (95% CI, 0.82–0.99) for FRA nonhomosexual men and 0.88 (95% CI, 0.79–0.98) for FRA women]. Similar results were obtained when time-dependent pVL undetectability was added to the model, although likelihood of CD4+ cell recovery was no longer significant in SSA/NFW men and women compared with FRA MSM. Although the differences were smaller, the immunological results were similar when the endpoint was a gain of 50 CD4+ cells within 6 months after cART initiation or a gain of 100 CD4+ cells within 1 year after cART initiation (data not shown). Results were similar when NFW individuals were excluded from the analyses (data not shown).
Clinical outcomes
During the 5 years after cART initiation, 460 individuals experienced a new AIDS-defining event (n = 445) or AIDS-related death (n = 15), within the first 6 months in 313 cases. The estimated cumulative incidences of a new AIDS-defining events or AIDS-related death were highest in SSA/NFW men and FRA nonhomosexual men, intermediate in SSA/NFW women, and lowest in FRA women and FRA MSM (Fig. 3a).
Fig. 3: Cumulative incidence of a new AIDS-defining event or AIDS-related death (a), a serious non-AIDS event or AIDS-unrelated death (b) and a new AIDS-defining event, serious non-AIDS event or death (c) after first-line cART initiation, according to origin, sex, and HIV transmission group (France, 2006–2012, n = 9746).cART, combination antiretroviral therapy; FRA, French natives; NFW, non-French West Indies; SSA, sub-Saharan Africa.
During the 5 years after cART initiation, 1430 individuals experienced a SNAE (n = 1392) or AIDS-unrelated death (n = 38), within the first 6 months in 666 cases. The estimated cumulative incidences of SNAE or AIDS-unrelated death were highest in SSA/NFW men and FRA nonhomosexual men, and lowest in SSA/NFW women, FRA women and FRA MSM (Fig. 3b).
Regarding first events occurring during the 5 years after cART initiation, 360 patients had a new AIDS-defining event, 1376 patients had a SNAE, and 38 patients died (six AIDS-related and 32 AIDS-unrelated). The principal new AIDS-defining events and AIDS-related deaths involved tuberculosis in 66 cases (18.0%), Kaposi's sarcoma in 50 cases (13.7%), and non-Hodgkin's lymphoma in 41 cases (11.2%). The principal SNAE and AIDS-unrelated deaths were severe infections in 478 cases (33.9%; 304 bacterial and 143 viral), cardiovascular disease in 124 cases (8.8%), malignancy in 102 cases (7.2%), iatrogenic effects in 87 cases (6.3%), gastrointestinal disorders in 87 cases (6.2%), and psychiatric disorders in 78 cases (5.5%). The estimated cumulative incidences of a first event were highest in SSA/NFW men and FRA nonhomosexual men, and lowest in SSA/NFW women, FRA women and FRA MSM (Fig. 3c).
Figure 4 shows crude and adjusted SHRs (aSHRs) and 95% CIs for the different negative clinical outcomes according to geographic origin, sex, and HIV transmission group. In crude analyses, by comparison with FRA MSM, all the patient groups had a significantly higher risk of a new AIDS-defining event, SNAE, or death. After adjustment for characteristics at cART initiation (model 1), the risk of a new AIDS-defining event, SNAE, or death was higher in FRA nonhomosexual men [aSHR, 1.18 (95% CI, 1.03–1.34)] and SSA/NFW men [1.18 (95% CI, 1.01–1.39)] than in FRA MSM. Compared with FRA MSM, all women, whatever their geographic origin, had no significant difference in risk of a new AIDS-defining event, SNAE, or death [aSHR, 1.12 (95% CI, 0.86–1.46)], whereas all nonhomosexual men, whatever their geographic origin, had a higher risk [aSHR, 1.37 (95% CI, 1.07–1.75), P = 0.0301].
Fig. 4: Crude and adjusted subhazard ratios for clinical outcomes after first-line cART initiation, according to geographic origin, sex, and HIV transmission group, in univariable and multivariable competing-risk regression analyses (France, 2006–2012, n = 9746).AIDS: new AIDS-defining event or AIDS-related death. Non-AIDS: serious non-AIDS event or AIDS-unrelated death. All: new AIDS-defining event, serious non-AIDS event, or death. Model 1: HR adjusted for characteristics at cART initiation. Model 2: model 1 + undetectable pVL as a time-dependent variable. Model 3: model 2 + CD4+ cell recovery at least 50/μl as a time-dependent variable. cART, combination antiretroviral therapy; FRA, French natives; NFW, non-French West-Indies; SHR, subhazard ratio; SSA, sub-Saharan Africa.
Similar results were obtained when time-dependent pVL undetectability was added to the model, alone or together with time-dependent CD4+ cell recovery of more than 50 cells/μl. Sensitivity analyses taking into account loss to follow-up (defined as any >18-month interruption) gave similar results. Results were similar when NFW individuals were excluded from the analyses (data not shown).
To identify parameters influencing the most the SHR for a new AIDS-defining event, SNAE, or death, we constructed bivariable models, including the ‘geographic origin, sex, and HIV transmission group’ combined variable and each individual studied risk factor at cART initiation. The parameters which altered the crude SHR by at least 5% were then gradually included in a model, along with the combined variable, and the step was repeated until no significant modification of the SHR was noted. Preexisting AIDS status, older age, and a lower CD4+ cell count at cART initiation had the biggest impact on the change between the crude and aSHRs of overall negative clinical outcome, the model including only these variables giving nearly the same SHRs for a new AIDS-defining event, SNAE, or death as the complete models (data no shown).
Discussion
Our results suggest that not all HIV-infected risk groups in France reap the same long-term benefits from cART. After first-line cART initiation, the likelihood of pVL undetectability was significantly lower in nonhomosexual men, whatever their geographic origin, than FRA MSM, and slightly lower in FRA women. No difference was observed between SSA/NFW women and FRA MSM. In patients with CD4+ cell counts below 500/μl at cART initiation, the likelihood of CD4+ cell recovery was slightly lower in nonmigrants, and 25–36% lower in migrants from SSA/NFW than in FRA MSM. The likelihood of a new AIDS-defining event, SNAE, or death was significantly higher in nonhomosexual men, whatever their geographic origin, than in FRA MSM, after accounting for viral suppression and CD4+ cell recovery.
A number of limitations to this study must be considered. First, no data on treatment adherence are available in the FHDH database. Moreover, we used an intent-to-continue-treatment approach, and cART interruption was not therefore taken into account in the models. However, loss to follow-up before the last database update and all follow-up interruption for more than 18 months (during the follow-up or before the last database update), which are both generally associated with poorer adherence, concerned 11.1 and 14.1% of the patients, respectively, and did not affect the results when they were added or removed to the clinical outcome models as a competing risk (data not shown). Similarly, socioeconomic factors and lifestyle factors, which could explain some differences between migrants and nonmigrants, and between men and women, are not recorded in the FHDH database, except data about alcohol and smoking which are only partly collected in the database since 2005. However, individuals originating from SSA/Haiti have a lower prevalence of smoking and alcohol consumption than nonmigrant individuals [35,36] and, if obesity is highly prevalent in migrant women from SSA/Haiti, men from SSA/Haiti have same rates of obesity than FRA men [35,37]. These lifestyles factors cannot explain alone the outcome differences between the different groups. Despite the censoring date for the study was relatively old, that is, 31 December 2012, universal treatment is recommended since the end of 2013 in France and new ART such as integrase inhibitors have been used only recently in France in naïve individuals. It is thus unlikely that the short available follow-up for the study after these changes would change the results. The main strength of the study is its large size and lengthy follow-up, which allowed us to assess meaningful clinical outcomes, including SNAEs in different subgroups.
After cART initiation, the likelihood of pVL undetectability was significantly lower in nonhomosexual men, whatever their geographic origin, and slightly lower in FRA women, than in FRA MSM. Previous studies showing similar virological responses to cART in heterosexual men and women, and poorer responses in these two groups than MSM, did not distinguish between migrants and nonmigrants [38–41]. Other studies have suggested that single male and female migrants and nonmigrant heterosexual men have lower probabilities of pVL undetectability than MSM on cART [11]. Although both male and female SSA migrants resident in France have more adverse living conditions than FRA MSM [42], migrant women had similar virological responses to FRA MSM, suggesting that socioeconomic conditions are not the sole explanation. It is possible that the need to care for children and/or the desire of pregnancy in the future in migrant women give motivation to a better adherence to cART despite lower socioeconomic conditions.
We found that likelihood of CD4+ cell recovery was lower in SSA/NFW migrants than in FRA MSM, and also slower than in FRA nonhomosexual men and FRA women (data not shown). These differences may have been because of lower baseline CD4+ cell counts and more frequent preexisting AIDS status in migrants incompletely controlled by adjustment on baseline values [6,9,29]. One other hypothesis could be that the intestinal microbiota, a major cause of chronic activation and impaired immune recovery on cART, differs between migrants and nonmigrants [43,44].
About two-thirds of all AIDS-defining events and AIDS-related deaths but only 47% of SNAEs and AIDS-unrelated deaths occurred within the first 6 months after cART initiation. Few deaths occurred but severe morbidity was frequent, mainly driven by SNAEs (particularly infections), which were more frequent than AIDS-defining events throughout the study period, as also observed in a study in which 90% of patients were on treatment in the period 2000–2008 [22] or among patients included in the Strategic Timing of Antiretroviral Therapy (START) study with a median baseline CD4+ cell count of 651/μl [26]. Older age, a lower CD4+ cell count and preexisting AIDS status at cART initiation had the biggest impact between the crude and aSHRs for overall negative clinical outcome. This emphasizes the need for early HIV diagnosis and immediate treatment [26]. Although CD4+ cell recovery was influenced by migration status but not by sex, nonhomosexual men, whatever their geographic origin, had a higher risk of a new AIDS-defining event, SNAE, or death than FRA MSM, whereas there were no significant differences between FRA or SSA/NFW migrant women and FRA MSM. In Western European countries, HIV-infected women have a higher life expectancy than HIV-infected men with same AIDS-related mortality but lower non-AIDS mortality rates [22,45,46]. However, when considering morbidity, women seem to have same rates of AIDS and non-AIDS morbidity than men [22] although no article assessed differences according to HIV transmission group and geographic origin. The France Recherche Nord&Sud Sida-hiv Hépatites -VIH: Enquête sur les personnes atteintes (ANRS -VESPA), a national cross-sectional study conducted in 2011 on a random stratified sample of individuals living with HIV in France, highlighted different socioeconomic patterns within the different HIV key populations: MSM had the best socioeconomic status, whereas intravenous drug users and migrants had the worst status [42]. Among heterosexual migrants and nonmigrants, women had slightly worse socioeconomic conditions than men and were more likely to live alone with children [42,47]. Apart from socioeconomic determinants and the baseline CD4+ cell count, factors such as lifestyle are probably important in explaining differences in clinical outcome [48].
Migrants from SSA/NFW initiated cART at lower CD4+ cell counts and had the lowest likelihood of CD4+ cell recovery compared with FRA MSM, but only being a nonhomosexual man (not geographic origin) had a negative impact on pVL undetectability and clinical outcome compared with FRA MSM. Better knowledge of socioeconomic and lifestyle factors influencing access to care, and implementation of current guidelines recommending early screening for HIV and routine immediate treatment, should help to reduce the differences in treatment response between different groups of patients.
Acknowledgments
We thank all the participants and research assistants of the French Hospital Database on HIV (FHDH).
Conceived and designed the experiments: L.A.D.M., D.C., and S.A. Performed the experiments: L.A.D.M. Analyzed the data: L.A.D.M., D.C., and S.A. Contributed reagents/materials/analysis tools: L.A.D.M. Wrote the study: L.A.D.M., D.C., and S.A. Has full access to all the data and takes the responsibility for the integrity of the data and the accuracy of the data analysis: L.A.D.M. Statistical expertise: D.C. and S.A. Interpretation of the data: L.A.D.M., S.M., J.G., J.P., P.D.T., S.G., O.L., J.L.M., M.A.K.J., D.R., A.S., A.M., R.D.S., D.C., and S.A. Drafted the article: L.A.D.M. and S.A. Critical revision of the article for important intellectual content: L.A.D.M., D.C., and S.A. Final approval of the article: L.A.D.M., S.M., J.G., J.P., P.D.T., S.G., O.L., J.L.M., M.A.K.J., D.R., A.S., A.M., R.D.S., D.C., and S.A.
Financial support and sponsorship: The FHDH is supported by the ANRS (’France REchercheNord&SudSida-hivHépatites’), INSERM, and the French Ministry of Health. L.A.D.M. is supported by a doctoral contract from Sorbonne Universités UPMC Paris Univ 06.
The Migrants Working Group of the FHDH-ANRS CO4: L.A.D.M. – Sorbonne Universités, UPMC Univ Paris 06, INSERM, Institut Pierre Louis d’épidémiologie et de Santé Publique (IPLESP UMRS 1136), F75013 Paris, France; S.M. – Sorbonne Paris cité, Université Paris Diderot, UMR 1137, Paris, France, AP-HP, Hôpital Bichat-Claude Bernard, Service des Maladies Infectieuses et Tropicales, Paris, France; J.G. – AP-HP, Hôpital Hôtel-Dieu, Unité d’immunoinfectiologie, Paris, France; J.P. – AP-HP, Hôpital Européen Georges Pompidou, Service d’immunologie clinique, Paris, France; P.D.T. – AP-HP, Hôpitaux Universitaires Paris-Ile de France-Ouest, Hôpital Raymond-Poincaré, Département de Médecine Aigüe Spécialisée, F-92380, Garches, France; S.G. – Sorbonne Universités, UPMC Univ Paris 06, INSERM, Institut Pierre Louis d’épidémiologie et de Santé Publique (IPLESP UMRS 1136), F75013 Paris, France, Université Paris Descartes, Sorbonne Paris cité, Paris, France,AP-HP, Groupe Hospitalier Cochin Broca Hôtel-Dieu, Unité de Biostatistique et Epidémiologie, Paris, France; O.L. – Université Paris Descartes, Sorbonne Paris cité, Paris, France, AP-HP, Hôpital Cochin, Paris, France; J.L.M. – AP-HP, Hôpital Saint Antoine, Service des Maladies Infectieuses et Tropicales, Paris, France; M.A.K.J. – Centre Hospitalier Saint-Denis, Hôpital Delafontaine, Service des Maladies Infectieuses et Tropicales, Saint-Denis, France; D.R. – Hôpitaux Universitaire Strasbourg, Centre de Soins de l’Infection par le VIH, F-67091, Strasbourg, France; A.S. – AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Département de médecine interne, Paris, France; A.M. – Centre Hospitalier Andrée Rosemon, Service des Maladies Infectieuses et Tropicales, Cayenne, France; R.D.S. – Sorbonne Universités, UPMC Univ Paris 06, INSERM, Institut Pierre Louis d’épidémiologie et de Santé Publique (IPLESP UMRS 1136), F75013 Paris, France; D.C. – Sorbonne Universités, UPMC Univ Paris 06, INSERM, Institut Pierre Louis d’épidémiologie et de Santé Publique (IPLESP UMRS 1136), F75013 Paris, France; S.A. – Sorbonne Universités, UPMC Univ Paris 06, INSERM, Institut Pierre Louis d’épidémiologie et de Santé Publique (IPLESP UMRS 1136), F75013 Paris, France (Present affiliation: Université Paris-Saclay, Univ. Paris-Sud, UVSQ, CESP INSERM U1018, Le Kremlin-Bicêtre, France), AP-HP, Hôpital Antoine Béclère, Service de Médecine interne/Immunologie clinique, F-92140, Clamart, France;
Members of the FHDH-ANRS CO4 are listed at http://www.ccde.fr/main.php?main_file=fl-1171464013–677.html
Clinical Epidemiology Group of the FHDH-ANRS CO4.
Scientific committee: S Abgrall, F Barin, E Billaud, F Boué, L Boyer, A Cabié, F Caby, A Canestri, D Costagliola, L Cotte, P De Truchis, X Duval, C Duvivier, P Enel, H Fischer, J Gasnault, C Gaud, J Gilquin, S Grabar, MA Khuong, O Launay, A Mahamat, M Mary-Krause, S Matheron, G Melica-Gregoire, H Melliez, JL Meynard, J Pavie, L Piroth, I Poizot-Martin, C Pradier, J Reynes, E Rouveix, A Simon, P Tattevin, H Tissot-Dupont, JP Viard.
COREVIH coordinating center: French Ministry of Health (G Astier, D Martin, I Prade), Technical Hospitalization Information Agency, ATIH (N Jacquemet).
Statistical analysis center: UMRS 1136 INSERM et UPMC (D Costagliola, Principal investigator, S Abgrall, S Grabar, M Guiguet, S Lang, 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: O Benveniste, A Simon, G Breton, C Lupin, E Bourzam; Hôpital Saint-Antoine: PM Girard, L Fonquernie, N Valin, B Lefebvre, M Sebire; Hôpital Tenon: G Pialoux, MG Lebrette, P Thibaut, A Adda, M Hamidi, J Cadranel, A Lavolé, A Parrot), Corevih Ile de France Est (Hôpital Saint-Louis: E Oksenhendler, L Gerard, JM Molina, W Rozenbaum, B Denis, N De Castro, C Lascoux; GH Lariboisière-Fernand Widal: JF Bergmann, V Delcey, A Lopes, P Sellier, M Parrinello; Hôpital Avicenne: O Bouchaud, N Vignier, F Méchaï, S Makhloufi, P Honoré; Hôpital Jean Verdier), Corevih Ile de France Nord (Hôpital Bichat-Claude Bernard: Y Yazdanpanah, S Matheron, S Lariven, V Joly, C Rioux; Hôpital Delafontaine: MA Khuong-Josses, M Poupard, B Taverne), Corevih Ile de France Ouest (Hôpital AmbroiseParé: E Roveix, S Greffe, C Dupont, A Freire Maresca, E Reimann; Hôpital Louis Mourier: M Bloch, F Meier, E Mortier, F Zeng, B Montoya; Hôpital Raymond Poincaré: C Perronne P de Truchis, D Mathez, D Marigot-Outtandy, H Berthé; CH André Mignot - Le Chesnay: A GrederBelan, A Therby, C Godin Collet, S Marque Juillet, M Ruquet, S Roussin-Bretagne, P Colardelle; Hôpital Foch – Suresnes: JE Kahn, D Zucman, C Majerholc, E Fourn, D Bornarel; Hôpital Victor Dupouy – Argenteuil: L Sutton, V Masse, P Genet, B Wifaq, J Gerbe; Hôpital Max Fourestier – Nanterre: V Daneluzzi, J Gerbe; CHI de Meulan les Mureaux: T Akpan, M Marcou; CH F Quesnay - Mantes La Jolie: F Granier, JJ Laurichesse, V Perronne; CHI de Poissy: C Veyssier-Belot, H Masson; CHI de St-Germain-en-Laye: Y Welker, P Brazille), Corevih Ile de France Sud (Hôpital Européen Georges Pompidou: L Weiss, J Pavie, Ml Lucas, C Jung, M Ptak; GH Tarnier-Cochin: D Salmon, C Le Jeunne, O Launay, P Guet, MP Pietri, E Pannier Metzger, V Marcou, P Loulergue, N Dupin, JP Morini, J Deleuze, P Gerhardt, J Chanal; HôtelDieu: JP Viard, J Ghosn, P Gazalet, A Cros, A Maignan; Hôpital Antoine Béclère: F Boué, S Abgrall, V Chambrin, I Kansau, M Raho-Moussa; Hôpital de Bicêtre: D Vittecoq, O Derradji, C Bolliot, C Goujard, E Teicher, J Gasnault, M Mole, K Bourdic; Hôpital Henri Mondor: JD Lelievre, G Melica, M Saidani, C Chesnel, C Dumont; Hôpital Necker: C Duvivier, O Lortholary, C Rouzaud, F Touam, K Benhadj; CMIP Pasteur: PH Consigny, P Bossi, A Gergely, G Cessot, F Durand).
Outside Paris area: Corevih Alsace (CHU de Strasbourg: D Rey, M Partisani, C Cheneau, ML Batard, P Fischer; CH de Mulhouse: G Beck-Wirth, C Michel, M Benomar), Corevih de l’Arc Alpin (CHU de Grenoble: P Leclercq, M Blanc, P Morand, O Epaulard, A Signori-Schmuck), Corevih Auvergne-Loire (CHU de Clermont-Ferrand: H Laurichesse, C Jacomet, M Vidal, D Coban, S Casanova; CHU de Saint-Etienne: A Fresard, C Guglielminotti, E Botelho-Nevers, A Brunon-Gagneux, V Ronat); Corevih Basse-Normandie (CHU de Caen: R Verdon, S Dargère, E Haustraete, P Féret, P Goubin), Corevih Bourgogne (CHU de Dijon: P Chavanet, A Fillion, L Piroth, D Croisier, S Gohier), Corevih Bretagne (CHU de Rennes: C Arvieux, F Souala, JM Chapplain, M Ratajczak, J Rohan), Corevih Centre et Poitou Charentes (CHRU de Tours), Corevih Franche-Comté (CHRU de Besançon: C Chirouze, L Hustache-Mathieu, JF Faucher, A Proust, N Magy-Bertrand, H Gil, N Méaux-Ruault; CH de Belfort: JP Faller, O Ruyer, V Gendrin, L Toko); Corevih Haute-Normandie (CHU de Rouen), Corevih Languedoc-Roussillon (CHU de Montpellier; CHU de Nîmes: A Sotto, I Rouanet, JM Mauboussin, R Doncesco, G Jacques), Corevih Lorraine Campagne-Ardennes (Nancy Hôpital de Brabois: T May, C Rabaud, M Andre, M Delestan, MP Bouillon; CHU de Reims: F Bani-Sadr, C Rouger, JL Berger, Y Nguyen), Corevih de Midi-Pyrénées Limousin (Toulouse CHU Purpan: B Marchou, P Delobel, G Martin Blondel, L Cuzin, N Biezunski, L Alric, D Bonnet, M Guivarch, A Palacin, V Payssan), Corevih Nord-Pas de Calais (CH de Tourcoing: H Melliez, F Ajana, A Meybeck, N Viget), Corevih PACA Est (Nice Hôpital Archet 1: C Pradier, P Pugliese, PM Roger, E Rosenthal, J Durant, E Cua, A Naqvi, I Perbost, K Risso; CH Antibes-Juan les Pins: D Quinsat; CHI de Fréjus/St Raphaël: P Del Giudice; CH de Grasse: PY Dides), Corevih PACA Ouest (Marseille Hôpital de la Conception: P Enel, R Sambuc, MS Antolini-Bouvenot, P Druart, L Meddeb, I Ravaux, A Menard, C Tomei, C Dhiver, H Tissot-Dupont; Marseille Hôpital Nord: J Moreau, S Mokhtari, MJ Soavi, V Thomas; Marseille Hôpital Sainte-Marguerite: I Poizot-Martin, S Bregigeon, O Faucher, V Obry-Roguet, AS Ritleng, N Petit; Marseille Centre pénitentiaire des Baumettes: C Bartoli, JM Ruiz, D Blanc; CH d’Aix-En-Provence: T Allegre, M Sordage, JM Riou, C Faudon; CH d’Avignon: B Slama, H Zerazhi, O Boulat, S Chebrek, M Beyrne; CH de Digne Les Bains: P Granet Brunello; CH de Gap: L Pellissier, D Bonnabel; CH de Martigues: R Cohen Valensi, B Mouchet, G Mboungou; CHI de Toulon: A Lafeuillade, E Hope-Rapp, G Hittinger, G Philip, V Lambry), Corevih Pays de la Loire (CHU de Nantes: F Raffi, C Allavena, E Billaud, N Hall, V Reliquet), Corevih de la Vallée du Rhône (Lyon Hôpital de la Croix-Rousse: C Chidiac, L Cotte, T Ferry, T Perpoint, P Miailhes; Lyon Hôpital Edouard Herriot: A Boibieux, JM Livrozet, D Makhloufi, F Brunel, P Chiarello).
Overseas: Corevih Guadeloupe (CHU de Pointe-à-Pitre: B Hoen, I Lamaury, I Fabre, K Samar, E Duvallon; CH Saint-Martin: C Clavel, S Stegmann, V Walter), Corevih Guyane (CH de Cayenne: M Nacher, L Adriouch, F Huber, V Vanticlke, P Couppié), Corevih Martinique (CHU de Fort-de-France: A Cabié, S Abel, S Pierre-François), Corevih de La Réunion (CHU Félix Guyon: C Gaud, C Ricaud, R Rodet, G Wartel,C Sautron; GH Sud Réunion: P Poubeau, G Borgherini, G Camuset).
Conflicts of interest
All authors declare no conflict of interest, although several members of the group have, at some stage in the past, received funding from a variety of pharmaceutical companies for research, travel grants, speaking engagements, or consultancy fees.
