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Comparative Biological and Clinical Outcomes after a Switch from a Virologically Unsuccessful First Protease Inhibitor–Containing Antiretroviral Combination to a 3-Drug Regimen Containing Efavirenz, Nevirapine, or Abacavir

  1. Sophie Abgrall1,3,
  2. Patrick G. Yeni2,
  3. Olivier Bouchaud3,
  4. Dominique Costagliola1, and
  5. Clinical Epidemiology Group of the French Hospital Database on HIV
  1. 1Institut National de la Santé et de la Recherche Médicale U720, Université Pierre et Marie Curie-Paris 6, Paris
  2. 2AP-HP, SMIT-A, Bichat-Claude Bernard Hospital, Paris
  3. 3Assistance Publique-Hôpital de Paris, Department of Infectious and Tropical Diseases, Avicenne Hospital, Bobigny, France
  1. Reprints or correspondence: Dr. S. Abgrall, INSERM U720, BP 335, 56 blvd. Vincent Auriol, 75625 Paris cedex 13, France (sophie.abgrall{at}ccde.chups.jussieu.fr).
 
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Abstract

Background. Incomplete adherence is the main cause of antiretroviral therapy failure during initial combination antiretroviral therapy (cART). A switch to a protease inhibitor—sparing cART may be useful when a patient does not tolerate a first protease inhibitor—containing cART regimen.

Methods. To compare the biological and clinical outcomes of patients in whom a first protease inhibitor—containing cART regimen failed to control viral replication and whose treatment was switched to cART containing efavirenz, nevirapine, or abacavir, we studied 1440 patients from the French Hospital Database on HIV whose treatment was changed from a first protease inhibitor—containing cART to a 3-drug regimen with either efavirenz, nevirapine, or abacavir while their plasma viral load was detectable.

Results. Kaplan-Meier 12-month probabilities of virological suppression were 73.6%, 53.9%, and 66.1% among patients whose treatment was switched to efavirenz-cART, nevirapine-cART, and abacavir-cART, respectively. Factors associated with a lower likelihood of virological suppression were antiretroviral exposure before the first cART, higher plasma viral load values at the treatment switch, a stavudine-lamivudine backbone after the switch (instead of a zidovudine-lamivudine backbone), and a switch to nevirapine (adjusted hazard ratio, 0.63 [95% CI, 0.54–0.74], compared with efavirenz) or abacavir (adjusted hazard ratio, 0.84 [95% CI, 0.68–1.04] compared with efavirenz). There was no difference among the 3 groups with regard to immunological gain (>50 CD4+ T cells/mm3) or clinical outcome.

Conclusion. When virological rebound occurs from receipt of protease inhibitor—containing cART, virological suppression can be obtained after a switch to a protease inhibitor—free cART—efavirenz-cART yielding the highest rate of virological suppression.

Combination antiretroviral therapy (cART) containing nonnucleoside reverse-transcriptase inhibitors (NNRTIs) or protease inhibitors (PIs) is currently recommended as initial treatment for immunodeficient, HIV-infected patients [1]. Incomplete adherence is the main cause of virological failure during initial cART [2]. Incomplete hadherence to treatment may be the result of poor tolerability or of a failure to grasp the importance of regular drug intake, and it can be corrected through treatment modification or counseling. In industrialized countries, second-line cART is chosen according to the individual patient's treatment history and resistance genotype and is aimed at driving plasma viral load (pVL) below the detection limit [1]. The use of a regimen containing at least 3 active drugs is currently recommended [1]. When genotyping is not available, 3 new antiretroviral drugs—at least 1 of which belongs to a new antiretroviral class—should be introduced, if possible [3]. Abacavir (ABC) is less susceptible than other nucleoside reverse-transcriptase inhibitors (NRTIs) to mutations that confer resistance to this drug class [4]; therefore, ABC preserves the effectiveness of other classes of antiretroviral drugs when it is associated with other NRTI backbones, and it maintains good blood lipid profiles [5]. A switch to PI-sparing cART containing NNRTIs or ABC can be useful when a patient does not tolerate PI-containing cART and has no history of NNRTI exposure or lengthy treatment with multiple NRTIs.

We studied the patients enrolled in the French Hospital Database on HIV whose therapy was switched from a first PI-containing cART to a 3-drug regimen containing efavirenz (EFV), nevirapine (NVP), or ABC at a time when their pVL was detectable, to identify factors associated with subsequent virological success. We also analyzed midterm immunological and clinical outcomes according to the switch regimen.

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Methods

Patients. The French Hospital Database on HIV is a large prospective cohort study of HIV-infected patients aged ⩾15 years who are treated in 68 French university hospitals. The enrollment criteria for inclusion in the French Hospital Database on HIV is documented HIV-1 or HIV-2 infection and written informed consent. Trained research assistants used the French Ministry of Health's DMI2 software, to prospectively collect and record clinical and biological data at inclusion and at each visit, at each hospital admission for an HIV-related clinical event, or with each new treatment prescription—or at least every 6 months—on standardized forms.

We selected HIV-1—infected patients who were enrolled in the French Hospital Database on HIV and who started a first PI-containing cART (at least 3 antiretroviral drugs with at least 2 NRTIs and 1 PI) after 1 January 1997. We excluded patients who had a history of exposure to PIs, NNRTIs, or ABC, as well as patients who were previously enrolled in blinded trials of antiretroviral drugs. We further selected patients whose treatment had subsequently been switched to a regimen containing 2 NRTIs plus 1 NNRTI or ABC at a time when the patients had a detectable pVL (⩾500 copies/mL), with no change in their antiretroviral therapy before the switch in therapy. The date of enrollment in this study was the date of the switch. Patients were excluded if CD4+ T cell counts or pVL values were unavailable within the 3-month period before the first cART and before the therapy switch or at least once during the follow-up period. The cutoff date for this analysis was 31 December 2003. A total of 1440 patients met these criteria.

Statistical analysis. Three groups of patients were compared after having undergone a switch in therapy to 3-drug cART containing EFV (EFV-cART), NVP (NVP-cART), or ABC (ABC-cART). Follow-up data were censored at the date of a subsequent change in antiretroviral therapy.

Factors associated with virological suppression, defined as the first pVL value <500 copies/mL, were identified using univariate and Cox multivariable proportional hazard models. Each variable with a P value <.20 for the association with virological suppression in the univariate model was included in a multivariable model in which the impact of the new therapy regimen on the occurrence of virological suppression was studied (after adjustment for other risk factors). Factors associated with immunological reconstitution (e.g., a gain of 50 CD4+ T cells/mm3 relative to baseline) and factors associated with new AIDS-defining events were also identified with Cox models. All models were stratified by the calendar year of the switch in therapy (7 strata from 1997 to 2003) to correct potential bias caused by a period effect.

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Results

Among the 1440 selected patients, 557 (39%) switched to EFV-cART, 637 (44%) switched to NVP-cART, and 246 (17%) switched to ABC-cART. The most frequently prescribed switch regimens were NVP-zidovudine-lamivudine (in 258 cases [18%]), ABC-zidovudine-lamivudine (in 193 cases [13%]), EFV-zidovudine-lamivudine (in 186 cases [13%]), EFV-stavudine-didanosine (in 162 cases [11%]), NVP-stavudine-didanosine (in 156 cases [11%]), NVP-stavudine-lamivudine (in 155 cases [11%]), and EFV-stavudine-lamivudine (in 118 cases [8%]).

The first cART was the patient's first antiretroviral treatment in 789 cases (55%). The other patients had previously received a median of 2 different antiretroviral drugs, for a median of 22 months (interquartile range [IQR], 11–39 months). The patient's first cART included lamivudine in 1153 cases (80%), zidovudine in 740 cases (51%), stavudine in 695 cases (48%), nelfinavir in 585 cases (41%), and indinavir in 606 cases (42%). The PI was boosted with ritonavir in 124 cases (9%).

Patients switched to the new PI-free cART a median of 15 months (IQR, 6–25 months) after starting their first PI-containing cART. Of these, 62 patients (4%) switched during the first month while receiving the PI-cART. Undetectable pVL occurred at least once during the first cART in 755 patients (52%). At the date of switch, 1339 patients (93%) had previously had at least 2 detectable pVLs. Patient characteristics are shown in table 1. Median follow-up after the switch in therapy was 31 months (IQR, 16–47 months).

Table 1
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Table 1

Characteristics of patients with a detectable plasma viral load at the time of change in therapy, according to the new antiretroviral regimen.

Virological outcome. Virological suppression (pVL value <500 copies/mL) was achieved in 835 patients. The Kaplan-Meier 12-month probability of virological suppression was 63.9% overall (95% CI, 61.0%–66.7%), 73.6% (95% CI, 69.5%–77.7%) for patients receiving EFV-cART, 53.9% (95% CI, 49.4%–58.3%) for patients receiving NVP-cART, and 66.1% (95% CI, 59.4%–72.8%) for patients receiving ABC-cART (P < .01). The 12-month probability of virological suppression among the 651 patients who were antiretroviral-experienced before their first cART was 58.0% (95% CI, 53.6%–62.3%), compared with 68.7% among the other 789 patients (95% CI, 65.0%–72.4%). The probability of virological suppression was significantly different between antiretroviral-experienced and antiretroviral-naive patients (P < .01).

After adjustment, the likelihood of virological suppression was 31% higher among antiretroviral-naive patients than among antiretroviral-experienced patients ( table 2). Higher pVL at the date of the change in therapy (but not at the date of the first cART) was associated with a lower likelihood of virological suppression (adjusted hazard ratio [aHR], 0.80 for pVL ⩾10,000 copies/mL vs. pVL <10,000 copies/mL). Compared with patients who had a zidovudine/lamivudine backbone after the change in therapy, the likelihood of virological suppression was 20% lower among patients with a stavudine/lamivudine backbone. Compared with patients whose treatment was switched to EFV-cART, patients whose treatment was switched to NVP-cART had a significantly lower likelihood of virological suppression (aHR, 0.63; 95% CI, 0.54–0.74), and patients whose treatment was switched to ABC-cART tended to have a lower likelihood of virological suppression (aHR, 0.84; 95% CI, 0.68–1.04). Similar results were found in both ARV-experienced and ARV-naive patients. Likewise, similar results were found when analysis was restricted to the 973 patients who received their first PI-containing cART for at least 6 months and who had at least 2 detectable pVLs before the change in therapy.

Table 2
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Table 2

Relative hazards of virological suppression and of new AIDS-defining events (ADEs) in patients who had a detectable plasma viral load at the time of change in therapy (1440 patients, 835 with virological suppression, and 123 new ADEs) and the results of multivariable Cox proportional hazards analysis (stratified by calendar year of the therapy switch).

Immunological outcome. Among patients who switched to EFV-cART, the median CD4+ T-cell counts at the change in therapy and 24 months later were 281 cells/mm3 (IQR, 157–450 cells/mm3) and 355 cells/mm3 (IQR, 190–474 cells/mm3), respectively. The respective values were 325 cells/mm3 (IQR, 207–492 cells/mm3) and 399 cells/mm3 (IQR, 220–565 cells/mm3) in patients who switched to NVP-cART, and 268 cells/mm3 (IQR, 150–407 cells/mm3) and 282 cells/mm3 (IQR, 78–433 cells/mm3) in patients who switched to ABC-cART.

During follow-up, 353 patients who switched to EFV-cART, 362 patients who switched to NVP-cART, and 137 patients who switched to ABC-cART gained at least 50 CD4+ T cells/mm3. Kaplan-Meier 24-month probabilities of this gain were 80.0% (95% CI, 75.3%–84.4%) with EFV-cART, 79.6% (95 % CI, 74.9%–84.3%) with NVP-cART, and 71.6% (95% CI, 64.0%–79.2%) with ABC-cART (P = .63). There were no differences in immunological outcome between the different regimen changes after adjustment for other variables (data not shown).

Clinical outcome. After the switch in therapy, a new AIDS-defining event occurred in 123 patients, of whom 50 were receiving EFV-cART, 55 were receiving NVP-cART, and 18 were receiving ABC-cART. Kaplan-Meier 24-month probabilities of a new AIDS-defining event were 8.7% (95% CI, 6.1%–11.2%), 5.8% (95% CI, 3.8%–7.7%) and 7.4% (95% CI, 3.4%–11.4%), respectively (P = .58).

After adjustment, patients with AIDS at the date of the switch in therapy, as well as patients with high pVL values (⩾10,000 copies/mL) when they started their first cART (aHR, 1.60 vs. pVLs <500 copies/mL) or when they switched treatments (aHR, 1.71 vs. pVLs <10,000 copies/mL), had a higher risk of a new AIDS-defining event, whereas patients with higher CD4+ T cell counts at the time of the switch in therapy (aHR, 0.30 for CD4+ T cell counts between 200 cells/mm3 and 350 cells/mm3 and 0.21 for CD4+ T cell counts >350 cells/mm3 vs. CD4+ T cell counts <50 cells/mm3) and patients with a stavudine/lamivudine backbone (aHR, 0.57 vs. patients with a zidovudine/lamivudine backbone) had a lower risk of a new AIDS-defining event ( table 2). Compared with patients who switched to EFV-cART, patients who switched to NVP-cART or ABC-cART had similar risk of a new AIDS-defining event (aHR, 1.03 [95% CI, 0.68–1.56] and 0.99 [95% CI, 0.55–1.78], respectively).

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Discussion

Among 1440 patients with a detectable pVL while receiving a first PI-containing cART, 12-month probabilities of virological suppression after a change in therapy to a 3-drug regimen containing EFV, NVP, or ABC were relatively high but were significantly different among the 3 regimens (73.6%, 53.9%, and 66.1%, respectively). In multivariable analysis, the likelihood of virological suppression was lower with NVP-cART and ABC-cART than with EFV-cART. No differences in immunological reconstitution or clinical outcome were observed among the 3 switch regimens.

Most patients had had at least 2 detectable pVLs before the switch, and more than one-half had an undetectable pVL at least once while receiving their first treatment. Therefore, patients underwent a change in cART at the time of a primary (without previous virological success) or a secondary (after a previous virological success) true virological failure of their first cART, rather than of a single blip of viral replication during a suboptimal treatment with no subsequent virological consequence. Moreover, when multivariable analysis of the factors associated with virological suppression was restricted to patients with a least a follow-up of 6 months while receiving their first PI-containing cART and at least 2 detectable pVLs before the switch in therapy, NVP-cART and ABC-cART were still associated with a lower likelihood of virological suppression than EFV-cART.

One-year Kaplan-Meier probabilities of the success rates of different cARTs were relatively high (∼64%), regardless of the switch regimen [6, 7]. It has been shown that the number of active drugs in a new regimen influences the likelihood of virological suppression [1, 8]. We did not have access to resistance genotyping data, but the practice of genotyping before a change in therapy became widespread in France after 1999 [9]; this may have contributed to the relatively high frequency of virological success in our cohort.

The first-line, PI-containing cART regimens mainly included nelfinavir or nonboosted indinavir (only 9% of patients received ritonavir-boosted PI therapy), both of which are no longer commonly used because of their lack of potency and their adverse effects. Although adherence data and data about the occurrence of adverse effects are not available in the French Hospital Database on HIV, virological failure, at least in ARV-naive patients, was possibly caused by a lack of drug potency leading to inadequate plasma concentrations or by poor adherence, rather than by resistance mutations [2]. The switch to a more potent and better-tolerated regimen was probably sufficient for some patients who did not have multiple resistance mutations.

The lamivudine/zidovudine/EFV combination is more effective than the lamivudine/zidovudine/ABC combination in antiretroviral-naive patients [10–12]. Our results confirm that, although a triple-NRTI combination with ABC may be an option for patients who are receiving an effective first PI-containing cART regimen [13], it should not be prescribed to patients who are experiencing virological failure or to patients who had received prior suboptimal NRTI therapy if other options are available [14]. Because ABC resistance develops slowly in vitro, and because multiple mutations are required to lower susceptibility to this drug [4], ABC can be used as a part of a more potent regimen that also includes an NNRTI or a new PI [15] or as a part of a 4-NRTI regimen [16].

Randomized trials have failed to show differences in virological outcome between EFV- and NVP-containing regimens in antiretroviral-naive patients [17]. Regarding PI-experienced patients, our results are consistent with those of studies showing a better response to EFV-containing cART than to NVP-containing cART [6, 18, 19]. One cohort study showed that patients switching to simpler therapy (in which the PI was replaced by EFV) had a lower virological failure rate than patients continuing to receive the PI [20]. Adherence was improved by reducing the pill burden and/or PI toxicity.

As in other studies, we found that previously untreated patients had a higher likelihood of virological suppression after the switch. In contrast, we failed to confirm the relation between a larger number of previously prescribed drugs and virological failure [8], but a regimen including a new class of antiretroviral drug or at least 3 new drugs is likely to have the best antiviral efficacy [15].

Immunological and clinical outcome (e.g., new AIDS-defining events) were similar, regardless of the switch regimen. Similar results were obtained in the EuroSIDA cohort, which involved more patients and longer follow-up times [21]. In the latter study, the latest pVL and CD4+ T cell count values explained the rates of AIDS and death in multivariable analysis, whereas the type of cART regimen had no independent impact. Because short- to midterm clinical outcome is best predicted by changes in the CD4+ T cell count, our study may have been too short to detect immunological or clinical differences between the 3 switch regimens.

The fact that the treatments were not randomly allocated in our study may have introduced a bias, although the treatment groups were fairly well balanced at baseline with regard to known predictors of virological outcome. More patients who were receiving EFV-cART than were receiving the other 2 regimens had low CD4+ T cell counts and/or had already had experienced an AIDS-defining event. Potential confounding factors were taken into account by multivariable analysis. The fact that difference in virological suppression between EFV-cART and NVP-cART was largely below 1.00 and was highly statistically significant despite the increased level of immunosuppression in patients in the EFV-cART group (leading to a probable disadvantage in global outcome), allows us to believe that there exists a real difference between these 2 drugs. Unmeasured confounding factors could have lead to an underestimation or an overestimation of the likelihood of virological suppression in the different switch regimens. However, Cox models were stratified by calendar year of switch to correct for potential bias associated with changes over time in antiretroviral prescriptions. Our study assessed midterm outcomes during a median follow-up of 31 months, and our results cannot be extrapolated to a longer follow-up. In the absence of equally large randomized trials, observational studies are the only means of identifying potential differences in rates of disease progression between antiretroviral regimens.

When virological rebound occurs during receipt of a PI-containing cART regimen, virological suppression can be obtained through the use of a PI-free cART regimen. After adjustment for other confounding factors, EFV-cART yielded a higher rate of virological suppression in our study than did NVP-cART. We did not attempt to determine whether the differences in virological outcome were caused by differences in adherence, toxicity, or intrinsic efficacy. Although ABC has a good resistance profile and is useful for salvage therapy, it cannot be recommended as part of a triple-NRTI regimen without the inclusion of a PI, an NNRTI, or a fourth potent NRTI.

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Clinical Epidemiology Group of The French Hospital Database On Hiv

Scientific committee. Dr. E. Billaud, Pr. F. Boué, D. Costagliola, Dr. X. Duval, Dr. C. Duvivier, Dr. P. Enel, Dr. S. Fournier, Dr. J. Gasnault, Dr. C. Gaud, Dr. J. Gilquin, Dr. S. Grabar, Dr. M.A. Khuong, Pr. J.M. Lang, M. Mary-Krause, Pr. S. Matheron, Pr. M.C. Meyohas, Pr. G. Pialoux, Dr. I. Poizot-Martin, Dr. C. Pradier, Pr. E. Rouveix, Pr. D. Salmon-Ceron, Pr. A. Sobel, Dr. P. Tattevin, Dr. H. Tissot-Dupont, and Dr. Y. Yasdanpanah.

Dossier médico-économique et épidémiologique de l'immunodéficience humaine 2 (DMI2) coordinating center. French Ministry of Health (Dr. E. Aronica, Dr. V. Tirard-Fleury, and I. Tortay).

Statistical analysis center. Institut National de la Santé et de la Recherche Médicale (INSERM) U720 (Dr. S. Abgrall, D. Costagliola, Dr. S. Grabar, M. Guiguet, E. Lanoy, H. Selinger-Leneman, L. Lièvre, M. Mary-Krause, V. Potard, and Dr. S. Saidi).

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

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

Overseas: CISIH de Guadeloupe (CHRU de Pointe-à-Pitre), CISIH de Guyane (CHG de Cayenne : Dr. M. Sobesky and Dr. R. Pradinaud), CISIH de Martinique (CHRU de Fort-de-France), CISIH de La Réunion (Centre Hospitalier Départemental [CHD] Félix Guyon: Dr. C. Gaud and Dr. M. Contant).

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Acknowledgements

We thank all participants of the French Hospital Database on HIV, and especially the research assistants, without whom this work would not have been possible.

Financial support. The French Hospital Database on HIV is supported by Institut National de la Santé et de la Recherche Médicale (INSERM), Agence Nationale de la Recherche sur le SIDA (ANRS), Fondation pour la Recherche Médicale (SIDACTION), and the French Ministry of Health.

Potential conflicts of interest. S.A. has received travel support from Bristol-Myers Squibb, GlaxoSmithKline, and Janssen-Cilag. P.G.Y. has received travel grants, consultancy fees, and honoraria from various pharmaceutical companies, including Abbott, GlaxoSmithKline, Bristol-Myers-Squibb, Gilead, Tibotec/Virco, Merck Sharp, and Dohme, Roche, and Boehringer-Ingelheim. D.C. has received travel grants, consultancy fees, and honoraria from various pharmaceutical companies, including Abbott, GlaxoSmithKline, Bristol-Myers-Squibb, Gilead, Roche, and Boehringer-Ingelheim. O.B.: no conflicts.

  • Received June 6, 2006.
  • Accepted August 21, 2006.
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  1. Clin Infect Dis. (2007) 44 (1): 120-127. doi: 10.1086/509578
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