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1. ABX464 (obefazimod) for patients with COVID-19 at risk for severe disease: miR-AGE, a randomized, double-blind placebo-controlled trial

Author

Pedro Giavina-Bianchi, MD, PhD, Eric Cua, MD, Karine Risso, MD, Véronique Mondain, MD, Anaïs Vissian, MSc, Cécile Joie, MSc, Philippe Pouletty, MD, Paul Gineste, PharmD, Hartmut J. Ehrlich, MD, PhD, and Jorge Kalil, MD, PhD

Subjects
ABX464, obefazimod, miR-124, COVID-19, Immunologic diseases. Allergy, RC581-607
Abstract

Background: ABX464 (obefazimod) is a small molecule that upregulates a single microRNA (miR-124) in immune cells and reduces the production of various inflammatory cytokines and chemokines. Objective: We assessed the efficacy and safety of the standard of care (SoC) plus oral obefazimod (SoC plus ABX464), 50 mg once daily, versus the SoC plus placebo for prevention of severe acute respiratory syndrome in patients with coronavirus disease 2019 (COVID-19) who are at risk for severe disease. Methods: Eligible patients for this phase 2/3 double-blind, placebo-controlled miR-AGE study were randomized (2:1) into 2 groups: SoC-ABX464 (n = 339) and SoC-placebo (n = 170). The primary end point was the percentage of patients who did not require use of high-flow oxygen or invasive or noninvasive mechanical ventilation within 28 days. The safety analyses included patients who had been randomly assigned and had received at least 1 dose of the study treatment. Results: At the time of the interim analysis, obefazimod showed no benefit over placebo when added to the SoC; the study enrollment was stopped for futility. The evaluation of the safety of obefazimod in 505 patients showed significantly more treatment-emergent adverse events in the SoC-ABX464 group than in the SoC-placebo group (P = .007). Frequently reported AEs in the SoC-ABX464 group included headache (14.6%), abdominal pain (9.6%), diarrhea (9.0%), back pain (6.9%), and nausea (6.0%). No treatment-related changes in laboratory parameters were reported. Conclusion: For patients who have severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and are at risk for severe COVID-19, obefazimod, 50 mg, provided no benefit over placebo when added to the SoC, although it did have a good safety profile (comparable to that reported in many therapeutic areas).

Published
2023
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2. Raltegravir 1200 mg once daily as maintenance therapy in virologically suppressed HIV-1 infected adults: QDISS open-label trial

Author

Nolwenn Hall, Clotilde Allavena, Christine Katlama, Alexandra Jobert, Jean-Michel Molina, Eric Cua, Firouzé Bani-Sadr, Laurent Hocqueloux, Claudine Duvivier, Dominique Merrien, Hitoto Hikombo, Elisabeth André-Garnier, Aurélie Gaultier, François Raffi, and the QDISS Study Group

Subjects
HIV-1 infection, Raltegravir, Once daily, Integrase inhibitor, Maintenance, Switch, Immunologic diseases. Allergy, RC581-607
Abstract

Abstract Background Raltegravir (RAL) has favorable tolerability and safety profile, with few and manageable drug interactions. The use of RAL 1200 mg once daily (qd) for first-line therapy is well established. We assessed efficacy and safety of RAL 1200 mg qd, as part of triple combined antiretroviral therapy (cART), for maintenance strategy. Methods The QDISS trial (NCT03195452) was a 48-week multicenter, single-arm, open-label study designed to evaluate the ability of 2 NRTIs + RAL 1200 mg qd to maintain virological suppression in HIV-1 infected subjects on a stable cART with 2 NRTIs and a third agent for at least 6 months. The primary endpoint was the proportion of participants with HIV-1 RNA

Published
2022
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3. Functional Exhaustion of Type I and II Interferons Production in Severe COVID-19 Patients

Author

Caroline Ruetsch, Vesna Brglez, Marion Crémoni, Kévin Zorzi, Céline Fernandez, Sonia Boyer-Suavet, Sylvia Benzaken, Elisa Demonchy, Karine Risso, Johan Courjon, Eric Cua, Carole Ichai, Jean Dellamonica, Thierry Passeron, and Barbara Seitz-Polski

Subjects
immunology, infectious diseases, COVID-19, interferon, personalized medicine, Medicine (General), R5-920
Abstract

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has emerged in Wuhan in December 2019 and has since spread across the world. Even though the majority of patients remain completely asymptomatic, some develop severe systemic complications. In this prospective study we compared the immunological profile of 101 COVID-19 patients with either mild, moderate or severe form of the disease according to the WHO classification, as well as of 50 healthy subjects, in order to identify functional immune factors independently associated with severe forms of COVID-19. Plasma cytokine levels, and cytokine levels upon in vitro non-specific stimulation of innate and adaptive immune cells, were measured at several time points during the course of the disease. As described previously, inflammatory cytokines IL1β, IL6, IL8, and TNFα associated with cytokine storm were significantly increased in the plasma of moderate and severe COVID-19 patients (p < 0.0001 for all cytokines). During follow-up, plasma IL6 levels decreased between the moment of admission to the hospital and at the last observation carried forward for patients with favorable outcome (p = 0.02148). After in vitro stimulation of immune cells from COVID-19 patients, reduced levels of both type I and type II interferons (IFNs) upon in vitro stimulation were correlated with increased disease severity [type I IFN (IFNα): p > 0.0001 mild vs. moderate and severe; type II IFN (IFNγ): p = 0.0002 mild vs. moderate and p < 0.0001 mild vs. severe] suggesting a functional exhaustion of IFNs production. Stimulated IFNα levels lower than 2.1 pg/ml and IFNγ levels lower than 15 IU/mL at admission to the hospital were associated with more complications during hospitalization (p = 0.0098 and p =0.0002, respectively). A low IFNγ level was also confirmed by multivariable analysis [p = 0.0349 OR = 0.98 (0.962; 0.999)] as an independent factor of complications. In vitro treatment with type IFNα restored type IFNγ secretion in COVID-19 patients while the secretion of pro-inflammatory cytokines IL6 and IL1β remained stable or decreased, respectively. These results (a) demonstrate a functional exhaustion of both innate and adaptive immune response in severe forms of COVID-19; (b) identify IFNα and IFNγ as new potential biomarkers of severity; and (c) highlight the importance of targeting IFNs when considering COVID-19 treatment in order to re-establish a normal balance between inflammatory and Th1 effector cytokines.

Published
2021
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4. High Prevalence of Acquired Thrombophilia Without Prognosis Value in Patients With Coronavirus Disease 2019

Author

Emile Ferrari, Benjamin Sartre, Fabien Squara, Julie Contenti, Celine Occelli, Fabien Lemoel, Jacques Levraut, Denis Doyen, Jean Dellamonica, Veronique Mondain, David Chirio, Karine Risso, Eric Cua, Jean Christophe Orban, Carole Ichai, Mohamed Labbaoui, Baptiste Mossaz, Pamela Moceri, Anny Appert‐Flory, Florence Fischer, and Pierre Toulon

Subjects
coronavirus disease 2019, thrombophilia, thrombosis, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract

Background Recent literature reports a strong thrombotic tendency in patients hospitalized for a coronavirus disease 2019 (COVID‐19) infection. This characteristic is unusual and seems specific to COVID‐19 infections, especially in their severe form. Viral infections can trigger acquired thrombophilia, which can then lead to thrombotic complications. We investigate for the presence of acquired thrombophilia, which could participate in this phenomenon, and report its prevalence. We also wonder if these thrombophilias participate in the bad prognosis of severe COVID‐19 infections. Methods and Results In 89 consecutive patients hospitalized for COVID‐19 infection, we found a 20% prevalence of PS (protein S) deficiency and a high (ie, 72%) prevalence of antiphospholipid antibodies: mainly lupus anticoagulant. The presence of PS deficiency or antiphospholipid antibodies was not linked with a prolonged activated partial thromboplastin time nor with D‐dimer, fibrinogen, or CRP (C‐reactive protein) concentrations. These coagulation abnormalities are also not linked with thrombotic clinical events occurring during hospitalization nor with mortality. Conclusions We assess a high prevalence of positive tests detecting thrombophilia in COVID‐19 infections. However, in our series, these acquired thrombophilias are not correlated with the severity of the disease nor with the occurrence of thrombotic events. Albeit the strong thrombotic tendency in COVID‐19 infections, the presence of frequent acquired thrombophilia may be part of the inflammation storm of COVID‐19 and should not systematically modify our strategy on prophylactic anticoagulant treatment, which is already revised upwards in this pathological condition. Registration URL: https://www.clini​caltr​ials.gov; Unique identifier: NCT04335162.

Published
2020
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5. Raltegravir Inclusion Decreases CD4 T-Cells Intra-Cellular Viral Load and Increases CD4 and CD28 Positive T-Cells in Selected HIV Patients

Author

Gaurav Kumar, Jacqueline Cottalorda-Dufayard, Rodolphe Garraffo, Francine De Salvador-Guillouët, Eric Cua, and Pierre-Marie Roger

Subjects
HIV infection, raltegravir, CD4 T-cells, pharmacokinetics, viral load, Cytology, QH573-671
Abstract

Raltegravir (RLT) prevents the integration of HIV DNA in the nucleus, but published studies remain controversial, suggesting that it does not decrease proviral DNA. However, there are only a few studies focused on virus-targeted cells. We aimed our study on the impact of RLT inclusion on total intra-cellular viral DNA (TID) in cellular subsets and immune effects in patients with newly acquired undetectable plasmatic viral load (UVL). Six patients having UVL using an antiretroviral combination for 6 months and CD4 T-cells > 350/mL and

Published
2022
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6. Pleasure and PrEP: Pleasure-Seeking Plays a Role in Prevention Choices and Could Lead to PrEP Initiation

Author

Xavier Mabire, Costanza Puppo, Stéphane Morel, Marion Mora, Daniela Rojas Castro, Julie Chas, Eric Cua, Claire Pintado, Marie Suzan-Monti, Bruno Spire, Jean-Michel Molina, and Marie Préau

Subjects
Medicine
Abstract

Pleasure-seeking plays a role in prevention (means choices and use), and in the sexual quality of life of men who have sex with men (MSM). Since HIV is a major threat to MSM health, new means of prevention, like pre-exposure prophylaxis (PrEP), must meet the needs of MSM to be fully efficient. Using a psychosocial approach, we examined how pleasure-seeking plays a role in participation of MSM in “ANRS-IPERGAY,” a community-based trial on sexual health which included sexual on-demand PrEP. Thirteen semistructured collective interviews were conducted with 45 participants. First, we analyzed participants’ search for new prevention means due to previous failures in condom use. We found that participants perceived condoms as a barrier—both materially and symbolically—to pleasure and desire, causing anxiety and stress considering sexual intercourse. Second, we explored representations and attitudes concerning pleasure within the context of PrEP. We found that PrEP allowed participants to freely choose their desired sexual positions and to better enjoy intimacy. Third, we studied the sexual quality of life for PrEP users in ANRS-IPERGAY and found an improvement. Thanks to the community-based design of the trial, this new prevention tool became a means to develop agency and empowerment for participants, not only in negotiating individual prevention but also in opposing the normative and stigmatizing discourse on sexuality and HIV. In conclusion, pleasure-seeking appears to be an essential element of sexual fulfillment that needs to be integrated as a positive notion in the study of HIV prevention.

Published
2019
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7. COPD in HIV-Infected Patients: CD4 Cell Count Highly Correlated.

Author

Karine Risso, Francine Guillouet-de-Salvador, Laure Valerio, Pascal Puglièse, Alissa Naqvi, Jacques Durant, Elisa Demonchy, Isabelle Perbost, Eric Cua, Charles-Hugo Marquette, and Pierre-Marie Roger

Subjects
Medicine, Science
Abstract

BACKGROUND:COPD is a frequent and significant cause of respiratory morbidity in HIV-infected patients despite the control of HIV. We aimed to analyze the factors correlated with COPD in this population to evaluate the existence of specific indicators of vulnerability in this population. METHODS AND FINDINGS:623 HIV-infected outpatients were enrolled during one year. This population was characterised by a dedicated questionnaire and electronic patient records. COPD screening was performed according to recommended spirometric criteria. The prevalence of COPD was 9.0%. Age and smoking were independently correlated with COPD (OR, 1.61 per 10 years increase, P = 0.007; OR, 1.28 per 10 pack-year increase, P = 0.003, respectively). Body mass index (BMI) and CD4 cell-count were independently and negatively correlated with COPD (OR, 0.78, P < 0.001; 0R, 0.77 per 100 cell/mm3 increase, P < 0.001, respectively). Among COPD patients, 77% did not know their diagnosis. Five COPD-patients never smoked and 44.2% did not have any respiratory symptoms and so were not eligible to perform a spirometry according to the guidelines. CONCLUSIONS:In addition to known risk factors, immune defect through CD4 cell count was independently and strongly correlated with COPD. COPD is largely underdiagnosed and thus unmanaged. However, early management and urgent smoking cessation are essential to improve prognosis. Clinicians' awareness on the particular vulnerability for COPD in HIV-infected patients is crucial. Moreover, indications to perform conventional spirometry to diagnose COPD may include more parameters than tobacco-smoking and respiratory complaints with a particular concern toward patients with a profound CD4 cell count defect.

Published
2017
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8. Missed opportunities for <scp>HIV</scp> pre‐exposure prophylaxis among people with recent <scp>HIV</scp> infection: The French <scp>ANRS</scp> 95041 <scp>OMaPrEP</scp> study

Author

Caroline Lions, Helene Laroche, Marion Mora, Gilles Pialoux, Laurent Cotte, Eric Cua, Lionel Piroth, Jean Michel Molina, Maria Salnikova, Gwenaëlle Maradan, Isabelle Poizot‐Martin, and Bruno Spire

Subjects
Infectious Diseases, Health Policy, Pharmacology (medical)
Abstract

Our objective was to identify missed opportunities for the use of pre-exposure prophylaxis (PrEP) in people with recently acquired HIV, factors associated with PrEP knowledge, and reasons for not using PrEP.This was a French national cross-sectional multicentre study enrolling people diagnosed with recent HIV (incomplete Western blot or negative HIV test in the previous 6 months) in 28 HIV clinical centres. Data were gathered using a self-administered questionnaire (SAQ).We analysed missed opportunities for PrEP use via a retrospective prep cascade. Factors associated with prior knowledge of PrEP and reasons for PrEP non-use among those who knew about PrEP were described using univariate and multivariate logistic regression models.Of the 224 eligible patients, 185 completed the SAQ and 168 (91%) were eligible for PrEP. Of these, 90% reported seeing at least one physician during the previous year, 26% received information about PrEP, and 5% used PrEP. Factors independently associated with a higher probability of knowing about PrEP were being a man who has sex with men, being aged 25-30 years (vs older), undergoing HIV screening at least once every semester (vs less often; odds ratio [OR] 4.11; 95% confidence interval [CI] 2.00-8.45), and practicing chemsex (OR 3.19; 95% CI 1.12-9.10). Fear of side effects and a low perceived risk of HIV infection were the two most common reasons for not using PrEP (N = 40 [33.33%] and N = 34 [28.3%], respectively).We found two gaps in the retrospective PrEP cascade: insufficient provision of PrEP information by healthcare providers (mainly general practitioners) and low PrEP acceptability by informed, eligible patients. More diverse healthcare providers need to be involved in PrEP prescription, and at-risk people need to be sensitized to the risk of HIV infection.

Published
2022
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9. Incidence and risk factors for recurrent sexually transmitted infections among MSM on HIV pre-exposure prophylaxis

Author

Jérémy, Zeggagh, Rebecca, Bauer, Constance, Delaugerre, Diane, Carette, Lisa, Fressard, Isabelle, Charreau, Christian, Chidiac, Gilles, Pialoux, Cécile, Tremblay, Eric, Cua, Olivier, Robineau, François, Raffi, Catherine, Capitant, Bruno, Spire, Laurence, Meyer, and Jean Michel, Molina

Subjects
Male, Incidence, Immunology, Sexually Transmitted Diseases, HIV Infections, Chlamydia Infections, Gonorrhea, Sexual and Gender Minorities, Infectious Diseases, Risk Factors, Humans, Immunology and Allergy, Female, Pre-Exposure Prophylaxis, Prospective Studies, Syphilis, Homosexuality, Male
Abstract

High rates of sexually transmitted infections (STIs) have been reported among pre-exposure prophylaxis (PrEP) users. We wished to assess the incidence and risk factors for recurrent STIs.The ANRS IPERGAY trial was a prospective study investigating PrEP among MSM and transgender women in outpatient clinics in France and Canada. In all, 429 participants were enrolled, offered up to 4 years of PrEP and screened for bacterial STIs (syphilis, chlamydia and gonorrhea) at baseline and every 6 months.STIs incidence was calculated yearly. Cox proportional hazards model regression was used to explore associations between participants characteristics at baseline and recurrent STI during follow-up.Over a median follow-up of 23 months, bacterial STI incidence was 75, 33, 13, 32 and 30 per 100 person-years for all STIs, rectal STIs, syphilis, gonorrhea and chlamydia, respectively. STI incidence significantly increased from the first year to the fourth year of the study (55 vs. 90 per 100 person-years, P 0.001). During the study period, 167 participants (39%) presented with more than one bacterial STIs which accounted for 86% of all STIs. Baseline risk factors associated with recurrent STIs in a multivariate analysis were an STI at baseline [hazards ratio: 1.48 (95% confidence interval (CI): 1.06-2.07), P = 0.02], more than eight sexual partners in prior 2 months [hazards ratio: 1.72 (95% CI: 1.21-2.43), P = 0.002] and the use of gamma-hydroxybutyrate [hazards ratio: 1.66 (95% CI: 1.16-2.38), P = 0.005].STI incidence was high and increased over time. Most STIs were concentrated in a high-risk group that should be targeted for future interventions.

Published
2022
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10. Long-term safety and efficacy of emtricitabine and tenofovir alafenamide vs emtricitabine and tenofovir disoproxil fumarate for HIV-1 pre-exposure prophylaxis: week 96 results from a randomised, double-blind, placebo-controlled, phase 3 trial

Author

Onyema Ogbuagu, Peter J Ruane, Daniel Podzamczer, Laura C Salazar, Keith Henry, David M Asmuth, David Wohl, Richard Gilson, Yongwu Shao, Ramin Ebrahimi, Stephanie Cox, Alexander Kintu, Christoph Carter, Moupali Das, Jared M Baeten, Diana M Brainard, Gary Whitlock, Jason M Brunetta, Gitte Kronborg, Christoph D Spinner, Andrea Antinori, Vanessa Apea, David Asmuth, Ann Avery, Paul Benson, Colm Bergin, Mezgebe Berhe, Indira Brar, Cynthia Brinson, Jason Brunetta, Jeffrey Burack, Thomas Campbell, Michelle Cespedes, Amanda Clarke, Megan Coleman, Josep Coll, Manuel Crespo Casal, Catherine Creticos, Gordon Crofoot, Frederick Cruickshank, Eric Cua, Eric Daar, Joseph de Wet, Edwin DeJesus, Jorge Del Romero Guerrero, William Dinges, Susanne Doblecki-Lewis, Taylor Donovan, Olamide Dosekun, Jason Flamm, Joel Gallant, Jan Gerstoft, Jay Gladstein, Robert Grant, Robert Grossberg, Bernhard Haas, Jason Halperin, W. David Hardy, Charles Hare, Shawn Hassler, Richard Hengel, William Henry, Theo Hodge, Sybil Hosek, Christopher Hurt, Michelle Iandiorio, Heiko Jessen, Stephen Kegg, Gabriele Knecht, Ivanka Krznaric, Anthony LaMarca, Carsten Schade Larsen, Olav Ditlevsen Larsen, Adriano Lazzarin, Clifford Leen, Christopher Lucasti, Patrick Mallon, Sharon Mannheimer, Martin Markowitz, Claudia Martorell, Kenneth Mayer, Anthony Mills, Jean-Michel Molina, Sheldon Morris, Karam Mounzer, Nneka Nwokolo, Olayemi Osiyemi, Andrew Petroll, Patrick Philibert, John Phoenix, Gilles Pialoux, Frank Post, Maria Prins, Moti Ramgopal, Bruce Rashbaum, Iain Reeves, Gary Richmond, Armin Rieger, Peter Ruane, Laura Salazar, Anthony Scarsella, Gabriel Schembri, Mia Scott, Peter Shalit, Gary Sinclair, Magdalena Sobieszczyk, Christoph Spinner, Jeffrey Stephens, Jason Szabo, Stephen Taylor, Melanie Thompson, Cecile Tremblay, Benoit Trottier, Gene Voskuhl, Barbara Wade, Kimberly Workowski, Sigal Yawetz, Benjamin Young, Infectious diseases, AII - Infectious diseases, and APH - Global Health

Subjects
Adult, Male, 0301 basic medicine, medicine.medical_specialty, Anti-HIV Agents, Epidemiology, Immunology, Organophosphonates, HIV Infections, Emtricitabine, Placebo, Tenofovir alafenamide, law.invention, Young Adult, 03 medical and health sciences, Pre-exposure prophylaxis, 0302 clinical medicine, Pharmacotherapy, Double-Blind Method, Randomized controlled trial, law, Virology, Internal medicine, medicine, Humans, 030212 general & internal medicine, Tenofovir, Aged, Alanine, business.industry, Adenine, Incidence (epidemiology), virus diseases, Middle Aged, 030112 virology, Clinical trial, Treatment Outcome, Infectious Diseases, HIV-1, Drug Therapy, Combination, Female, Pre-Exposure Prophylaxis, business, Follow-Up Studies, medicine.drug
Abstract

Summary Background In DISCOVER, a multinational, randomised controlled trial, emtricitabine and tenofovir alafenamide compared with emtricitabine and tenofovir disoproxil fumarate showed non-inferior efficacy for HIV prevention and improved bone mineral density and renal safety biomarkers at week 48. We report outcomes analysed after all participants had completed 96 weeks of follow-up. Methods This study is an ongoing, randomised, double-blind, multicentre, active-controlled, phase 3, non-inferiority trial done at 94 community, public health, and hospital-associated clinics located in Europe and North America. Adult cisgender men and transgender women who have sex with men, both with a high risk of acquiring HIV as determined by self-reported sexual behaviour or recent sexually transmitted infections, were randomly assigned (1:1) to receive either emtricitabine and tenofovir alafenamide (200/25 mg) tablets daily, with matched placebo tablets (emtricitabine and tenofovir alafenamide group), or emtricitabine and tenofovir disoproxil fumarate (200/300 mg) tablets daily, with matched placebo tablets (emtricitabine and tenofovir disoproxil fumarate group). The primary efficacy outcome was incident HIV infection. Incidence of HIV-1 infection per 100 person-years was assessed when the last participant had completed 96 weeks of follow-up. This trial is registered with ClinicalTrials.gov , number NCT02842086 . Findings Between Sept 13, 2016, and June 30, 2017, 5387 participants were randomly assigned to receive emtricitabine and tenofovir alafenamide (n=2694) or emtricitabine and tenofovir disoproxil fumarate (n=2693), contributing 10 081 person-years of follow-up. At 96 weeks of follow-up, there were eight HIV infections in participants who had received emtricitabine and tenofovir alafenamide (0·16 infections per 100 person-years [95% CI 0·07–0·31]) and 15 in participants who had received emtricitabine and tenofovir disoproxil fumarate (0·30 infections per 100 person-years [0·17–0·49]). Emtricitabine and tenofovir alafenamide maintained its non-inferiority to emtricitabine and tenofovir disoproxil fumarate for HIV prevention (IRR 0·54 [95% CI 0·23–1·26]). Approximately 78–82% of participants reported taking study medication more than 95% of the time across all study visits. Rates of sexually transmitted infections remained high and similar across groups (21 cases per 100 person-years for rectal gonorrhoea and 28 cases per 100 person-years for rectal chlamydia). Emtricitabine and tenofovir alafenamide continued to show superiority over emtricitabine and tenofovir disoproxil fumarate in all but one of the six prespecified bone mineral density and renal biomarkers. There was more weight gain among participants who had received emtricitabine and tenofovir alafenamide (median weight gain 1·7 kg vs 0·5 kg, p Interpretation Emtricitabine and tenofovir alafenamide is safe and effective for longer-term pre-exposure prophylaxis in cisgender men and transgender women who have sex with men. Funding Gilead Sciences.

Published
2021
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11. Dolutegravir-based dual maintenance regimens combined with lamivudine/emtricitabine or rilpivirine: risk of virological failure in a real-life setting

Author

Caroline Lions, N Biezunski, Sophie Matheron, Romain Guery, Pierre-Marie Roger, Caroline Charlier, Mathieu Dupont, Line Meddeb, Philippe Van de Perre, V Joly, R Lecomte, Matthieu Revest, Claudine Duvivier, B Lefèvre, M Delestan, H Laurichesse, H Marty, F Lemaitre, Martine Valette, Marc-Antoine Valantin, A S Ritleng, A Ménard, Eric Cua, M. Alvarez, A Raoux, M P Bouillon, A Sève, A Brebion, Claire Triffault-Fillit, Sylvie Bregigeon, M Carles, O. Aubry, S Hénard, P. Dellamonica, A Charmillon, E Alidjinou, V Brodard, M Tetart, F Raffi, Paul-Henri Consigny, O Lesens, C Brunet-Cartier, I Lamaury, S Giaché, Amandine Gagneux-Brunon, Jacques Reynes, Karine Sauné, Clotilde Allavena, Q Lepiller, Véronique Reliquet, C Louisin, I Perbost, Jean-Luc Berger, B Prouvost-Keller, Eric Delaporte, Isabelle Lamaury, C Gubavu, L Fagour, Laurent Cotte, G Gaube, Elina Teicher, Faouzi Souala, C Blanc, Dominique Merrien, Isabelle Poizot-Martin, C Drobacheff-Thiébaut, T May, P Richard, M A Trabaud, M Bistoquet, C Klotz, Samira Fafi-Kremer, M Marcel, Charlotte Charpentier, L Lelièvre, K Risso, Sandrine Pierre-François, S Ferrando, S Breaud, S Bevilacqua, A Montoya Ferrer, T Rojas-Rojas, D Boucher, Yazdan Yazdanpanah, Olivier Lortholary, Philippe Colson, Anne-Sophie Brunel, F-Xavier Lescure, Christelle Tomei, M Martin-Degioanni, Eric Rosenthal, Philippe Bossi, Patrick Miailhes, Kevin Bouiller, Lise Cuzin, A Foltzer, F Boulard, Michel Vidal, V Mondain, H Colson, J Pasquier, I Kmiec, F Alby-Laurent, R Agher, A Cabié, Guillaume Martin-Blondel, L Hocqueloux, M Colin, A Madrid, Faiza Ajana, J M Livrozet, V Rio, Karima Amazzough, C Merle de Boever, M Digumber, Thomas Perpoint, A Cheret, Laurence Bocket, Z Julia, Virginie Ferré, M Pradier, M Poisson-Vannier, A Legoff, M J Soavi, Y Quertainmont, Marine Morrier, Christian Chidiac, F Touam, O Zaegel-Faucher, A Marquise, G Benabdelmoumen, Florence Ader, T Guimard, M C Receveur, J C Tardy, P Morineau, K Guitteaud, D. Rey, S Leautez, Catherine Chirouze, Benoit Tressières, A. Ivanova, C Charre, J Reynes, Christian Pradier, Catherine Dhiver, Laurent Boyer, E Frentiu, David Rey, C Allavena, Anne Motte, Tristan Ferry, C Pronier, M. Hentzien, C Rouzaud, O Cabras, K Jidar, F Najioullah, C Clavel, M Orticoni, S Patrat-Delon, M Cavellec, Cécile Herrmann-Storck, V Baclet, Jade Ghosn, M Perry, S Wehrlen-Pugliese, J. M. Chapplain, R Palich, Laurent Hocqueloux, A Maillard, C Deschanvres, O Deradji, F. Lucht, A Grégoire, Veronique Joly, R Ouissa, C Daniel, N Mrozek, D Chirio, O Bollangier, J Bavay, P. Le Turnier, A Maka, C Rioux, Colin Deschanvres, C Brochier, Elisabeth Botelho-Nevers, A Meybeck, C Ceppi, J Lourenco, François Bénézit, Thomas Jovelin, G Zouzou, N Tissot, N. Viget, F Brunel-Dalmas, Brigitte Montes, N Chellum Rungen, K Rome, David Boutoille, B Bigeard, I Fabre, N Oran, M Lefebvre, P Point, C Etienne, Diane Descamps, G Thomas, S Le Gac, Cyrille Delpierre, Pierre Tattevin, M Godinot, P Fischer, C Aumeran, C Boulard, Elisabeth André-Garnier, J Sinteff, V Ronat, F Goehringer, Romain Palich, Luminita Schneider, I Touitou, Eric Billaud, P Thill, Catherine Varache, Olivier Robineau, I Jaquet, Roland Landman, Cédric Arvieux, B. Bonnet, V Rzepecki, Olivier Grossi, Christian Rabaud, L Laine, F Louni, C Cheneau, S Markowicz, Hélène Laroche, A Gervais, C Bernard-Henry, E Goncalvez, N Lerolle, M André, D Lambert, André Boibieux, L. Porte, S Bouchez, E Paredes, E Aïssi, V. Le Moing, S Degroodt, Sylvie Abel, André Cabié, B Lafon-Desmurs, O Babre, M Baldeyrou, C Debreux, A Rodallec, Pierre Delobel, V Icard, Agathe Becker, Edouard Tuaillon, Hervé Tissot-Dupont, M Mokhtari, C Morlat, I Alcaraz, Anne Frésard, O Cannesson, Elodie Curlier, P Chiarello, S. Roux, F Bani-Sadr, François Raffi, Florent Valour, M Piffaut, M Priester, A. Belkhir, J Romaru, Cécile Goujard, A Castro, G Cessot, A Mirand, C Pouderoux, A Brunet, C Michelangeli, Y N’guyen, Patrice Muret, Elisa Demonchy, Christine Jacomet, D Makhloufi, E Jeanmaire, Marialuisa Partisani, Véronique Obry-Roguet, J Turmel, C Mélounou, J. Durant, Christine Katlama, P Parize, O Robineau, S Seang, F. Bozon, S Galie, Alexa Debard, E de Mautort, C Duvivier, Fanny Lanternier, Alain Makinson, A Barrail-Tran, C Aguilar, A Naqvi, Rodolphe Garraffo, N Meftah, C Biron, A de Monte, Pascal Pugliese, V Corbin, S Jaureguiberry, E Lafont, L Hustache Mathieu, R Colarino, Isabelle Ravaux, C Henquell, Benoit Pilmis, M Grégoire, P Lansalot, E Ressiot, T. Huleux, Olivier Baud, S Sécher, R Dupin de Majoubert, J Leporrier, L Cuzin, E Chevalier, M Poinot, R Tubiana, S Lariven, A Boucher, N Atoui, Firouzé Bani-Sadr, T Prazuck, M Ducassou, Gilles Peytavin, A Soria, B J Gaborit, Service des maladies infectieuses et tropicales [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Dat’AIDS Study Group, Département Maladies Infectieuses et Tropicales, Hôpital Universitaire, Montpellier, France, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques et émergentes (TransVIHMI), Institut de Recherche pour le Développement (IRD)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), CHU Pointe-à-Pitre/Abymes [Guadeloupe], Les Hôptaux universitaires de Strasbourg (HUS), CHU Strasbourg, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Universitaire de Reims (CHU Reims), Centre Hospitalier Gustave Dron [Tourcoing], Institut Pasteur [Paris] (IP), Centre Hospitalier Régional d'Orléans (CHRO), Centre d'Epidémiologie et de Recherche en santé des POPulations (CERPOP), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU de la Martinique [Fort de France], AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Universitaire de Martinique [Fort-de-France, Martinique], CHU Clermont-Ferrand, and Université Clermont Auvergne (UCA)

Subjects
Microbiology (medical), medicine.medical_specialty, Anti-HIV Agents, Pyridones, MESH: Piperazines, HIV Infections, Emtricitabine, Piperazines, law.invention, chemistry.chemical_compound, Randomized controlled trial, law, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Internal medicine, MESH: Pyridones, Oxazines, MESH: Emtricitabine, Humans, Medicine, Pharmacology (medical), MESH: Anti-HIV Agents, Pharmacology, MESH: Heterocyclic Compounds, 3-Ring, MESH: Humans, business.industry, Rilpivirine, Lamivudine, MESH: HIV Infections, Viral Load, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, Virological failure, Regimen, Infectious Diseases, chemistry, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Dolutegravir, Cohort, MESH: Rilpivirine, business, MESH: Viral Load, Heterocyclic Compounds, 3-Ring, MESH: Oxazines, medicine.drug, MESH: Lamivudine
Abstract

Background Maintenance ART with dolutegravir-based dual regimens have proved their efficacy among HIV-1-infected subjects in randomized trials. However, real-life data are scarce, with limited populations and follow-up. Objectives We assessed virological failure (VF) and resistance-associated mutations (RAMs) on dolutegravir maintenance regimens in combination with rilpivirine or with lamivudine or emtricitabine (xTC) and analysed the factors associated with VF. Methods Between 2014 and 2018, all HIV-1-infected adults included in the Dat’AIDS cohort and starting dolutegravir/rilpivirine or dolutegravir/xTC as a maintenance dolutegravir-based dual regimen were selected. VF was defined as two consecutive HIV RNA values >50 copies/mL or a single value >400 copies/mL. We compared cumulative genotypes before initiation of a maintenance dolutegravir-based dual regimen with genotype at VF. Results We analysed 1374 subjects (799 on dolutegravir/rilpivirine and 575 on dolutegravir/xTC) with a median follow-up of 20 months (IQR = 11–31) and 19 months (IQR = 11–31), respectively. VF occurred in 3.8% (n = 30) of dolutegravir/rilpivirine subjects and 2.6% (n = 15) of dolutegravir/xTC subjects. Among subjects receiving dolutegravir/rilpivirine, two genotypes harboured emerging RAMs at VF: E138K on NNRTI (n = 1); and E138K+K101E on NNRTI and N155H on INSTI (n = 1). Among subjects receiving dolutegravir/xTC, no new RAM was detected. The only predictive factor of VF on dolutegravir/rilpivirine was the history of failure on an NNRTI-based regimen (adjusted HR = 2.97, 95% CI = 1.28–6.93). No factor was associated with VF on dolutegravir/xTC. Conclusions In this large real-life cohort, dolutegravir/rilpivirine and dolutegravir/xTC sustained virological suppression and were associated with a low rate of VF and RAM emergence. Careful virological screening is essential before switching to dolutegravir/rilpivirine in virologically suppressed patients with a history of NNRTI therapy.

Published
2022
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12. Risk factors for HIV infection among men who have sex with men in the ANRS IPERGAY PrEP trial

Author

Cécile Tremblay, F Raffi, Jean-Michel Molina, Eric Cua, Julie Chas, Guillemette Antoni, Isabelle Charreau, Bruno Spire, Laurence Meyer, Constance Delaugerre, Julien Gras, Christian Chidiac, Marine Pillet, Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Génomes, biologie cellulaire et thérapeutiques (GenCellDi (U944 / UMR7212)), Collège de France (CdF (institution))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Institut de Recherche Saint-Louis - Hématologie Immunologie Oncologie (Département de recherche de l’UFR de médecine, ex- Institut Universitaire Hématologie-IUH) (IRSL), Université Paris Cité (UPCité), Essais Thérapeutiques et Maladies Infectieuses, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Nice (CHU Nice), Centre hospitalier universitaire de Nantes (CHU Nantes), Université de Lyon, CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital du Sacré-Coeur de Montréal, Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U1252 INSERM - Aix Marseille Univ - UMR 259 IRD), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Malbec, Odile

Subjects
Male, medicine.medical_specialty, Anti-HIV Agents, Sexual Behavior, [SDV]Life Sciences [q-bio], Human immunodeficiency virus (HIV), Dermatology, medicine.disease_cause, Placebo, Men who have sex with men, Sexual and Gender Minorities, Pre-exposure prophylaxis, Internal medicine, medicine, Emtricitabine, Humans, risk factors, Homosexuality, Male, Hiv acquisition, Medical prescription, pre-exposure prophylaxis, Illicit Drugs, business.industry, sexual behaviour, [SDV] Life Sciences [q-bio], Infectious Diseases, Baseline characteristics, business, Anal sex, HIV infections
Abstract

ObjectivesWe aimed to assess among men who have sex with men (MSM) risk factors for HIV infection, to identify those who require urgent pre-exposure prophylaxis (PrEP) prescription.MethodsAll participants enrolled in the placebo arm of the ANRS IPERGAY trial, or infected between screening and day 0, were included. Baseline characteristics were described and HIV incidence rate ratios (RRs) were estimated with their 95% CIs.Results203 MSM were included with a median follow-up of 9 months. During the study period, 16 participants acquired HIV infection while not receiving tenofovir disoproxil and emtricitabin (TDF/FTC) over 212.4 person-years (PYs) of follow-up (incidence rate 7.5/100 PYs, 95% CI: 4.3 to 12.2). Being enrolled in Paris was associated with a significant increased risk of HIV infection (RR: 4.1; 95% CI: 1.1 to 28.3). A high number of sexual partners in prior 2 months (≥10 vs <5) and of condomless receptive anal sex episodes in prior 12 months (>5 vs ConclusionsMSM who have frequent condomless receptive anal sex and multiple partners, or use recreational drugs should be targeted in priority for PrEP prescription especially if they live in an area with a high prevalence of HIV infection.

Published
2021
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13. Raltegravir 1200 mg Once Daily as Maintenance Therapy in Virologically Suppressed HIV-1 Infected Adults : QDISS Open-Label Trial

Author

Elisabeth André-Garnier, Hitoto Hikombo, Clotilde Allavena, Christine Katlama, Claudine Duvivier, Dominique Merrien, François Raffi, Firouzé Bani-Sadr, Alexandra Jobert, Jean-Michel Molina, Aurélie Gaultier, Laurent Hocqueloux, Eric Cua, and Nolwenn Hall

Subjects
medicine.medical_specialty, Maintenance therapy, business.industry, Internal medicine, medicine, Human immunodeficiency virus (HIV), Once daily, Open label, business, Raltegravir, medicine.disease_cause, medicine.drug
Abstract

Background: Raltegravir (RAL) has favorable tolerability and safety profile, with few and manageable drug interactions. The use of RAL 1200 mg once daily (qd) for first-line therapy is well established. We assessed efficacy and safety of RAL 1200 mg qd, as part of triple cART, for maintenance strategy.Methods: The QDISS trial (NCT03195452) was a 48-week multicenter, single-arm, open-label study designed to evaluate the ability of 2 NRTIs + RAL 1200 mg qd to maintain virological suppression in HIV-1 infected subjects on a stable cART with 2 NRTIs and a third agent for at least 6 months. The primary endpoint was the proportion of participants with HIV-1 RNA p=0.023) and LDL-cholesterol (p=0.009) decreased, lifestyle and ease subscale significantly improved (p=0.04). The quality of life and Patients Reported Outcomes (PROs) also improved at W12 (p=0.007). Conclusion: RAL 1200 mg qd as part of a maintenance triple therapy showed a high efficacy in virologically suppressed HIV-1 infected subjects, with good safety profile and improved lipid profile and patient reported outcomes.Trial registration = clinical trials.gov NCT03195452 and EudraCT 2016-003702-13

Published
2021
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14. Estimated pill intake with on-demand PrEP with oral TDF/FTC using TFV-DP concentration in dried blood spots in the ANRS IPERGAY trial

Author

Rebecca Bauer, Samia Mourah, Gilles Pialou, Jean-Michel Molina, Aïcha Laghzal, Peter L. Anderson, Eric Cua, Laurent Cotte, Lane Buschman, Geoffroy Liegeon, Lauriane Goldwirt, Isabelle Charreau, Laurence Meyer, and Constance Delaugerre

Subjects
Adult, Male, Microbiology (medical), medicine.medical_specialty, Multivariate analysis, Anti-HIV Agents, HIV Infections, Logistic regression, Emtricitabine, Medication Adherence, Men who have sex with men, Sexual and Gender Minorities, 03 medical and health sciences, Pre-exposure prophylaxis, 0302 clinical medicine, Pharmacokinetics, Internal medicine, Humans, Medicine, Pharmacology (medical), 030212 general & internal medicine, Homosexuality, Male, Tenofovir, Pharmacology, 0303 health sciences, 030306 microbiology, business.industry, Adenine, Organophosphates, Infectious Diseases, Pill, Female, Pre-Exposure Prophylaxis, Median body, business, medicine.drug
Abstract

Background Tenofovir diphosphate (TFV-DP) concentration in dried blood spots (DBSs) is a reliable pharmacokinetics biomarker of adherence to tenofovir disoproxil fumarate (TDF). We aimed to use DBSs to estimate pill intake among participants using on-demand pre-exposure prophylaxis (PrEP) and to identify predictive factors associated with higher TFV-DP concentrations. Methods DBSs were collected at the last study visit of the open-label phase of the ANRS IPERGAY study, assessing on-demand oral TDF/emtricitabine for PrEP among MSM and transgender female participants. We quantified TFV-DP in DBSs centrally. We assessed correlation between pill count and TFV-DP concentration by Spearman correlation and explored associations between participant demographics, sexual behaviour and PrEP use during sexual intercourse (SI) with TFV-DP concentrations by univariate and multivariate logistic regression models. Results The median age of the 245 participants included in this study was 40 years, with a median body weight of 73 kg. Median (IQR) TFV-DP concentration reached 517 (128–868) fmol/punch, corresponding to an estimated intake of 8–12 tablets per month (2–3 doses per week). Only 39% of participants had a TFV-DP concentration above 700 fmol/punch. TFV-DP concentrations were moderately correlated with pill count (r: 0.59; P This is a pre-copyedited, author-produced PDF of an article accepted for publication in Journal of Antimicrobial Chemotherapy following peer review. The version of record [Estimated pill intake with on-demand PrEP with oral TDF/FTC using TFV-DP concentration in dried blood spots in the ANRS IPERGAY trial. Journal of Antimicrobial Chemotherapy (2021)] is available online at: https://doi.org/10.1093/jac/dkab253. Deposited by shareyourpaper.org and openaccessbutton.org. We've taken reasonable steps to ensure this content doesn't violate copyright. However, if you think it does you can request a takedown by emailing help@openaccessbutton.org.

Published
2021
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15. HIV-1-RNA and total HIV-1-DNA loads in the genital compartment in men receiving dolutegravir- versus darunavir-based combined ART (cART) regimens during primary HIV infection

Author

Alice-Andrée Mariaggi, Rebecca Bauer, Caroline Charre, Elise Gardiennet, Vincent Meiffredy, Faiza Ajana, Karine Lacombe, Gilles Pialoux, Eric Cua, Christine Rouzioux, Laurence Meyer, Antoine Cheret, and Véronique Avettand-Fenoel

Subjects
Pharmacology, Microbiology (medical), Male, Pyridones, virus diseases, HIV Infections, DNA, Piperazines, Infectious Diseases, Oxazines, HIV-1, Humans, RNA, Viral, Pharmacology (medical), Genitalia, Heterocyclic Compounds, 3-Ring, Darunavir
Abstract

Background Dolutegravir is a widespread integrase strand-transfer inhibitor (INSTI) recommended for treatment of primary HIV infection (PHI). PHI is a high-risk stage for sexual transmission because of the high viral load in semen. Yet dolutegravir concentrations in semen are lower than in blood during chronic treatment. Objectives To compare the kinetics of HIV-RNA and total HIV-DNA in the genital compartment in subjects receiving either tenofovir/emtricitabine/dolutegravir or tenofovir/emtricitabine/darunavir/cobicistat as a first-line combined ART (cART) at the time of PHI. Patients and methods Eighteen subjects receiving tenofovir/emtricitabine/dolutegravir and 19 receiving tenofovir/emtricitabine/darunavir/cobicistat enrolled in the ANRS169 OPTIPRIM-2 trial participated in the genital substudy. Results Between week (W) 0 and W2 HIV-RNA in seminal plasma (SP) decreased by 1 log10 copies/mL. Undetectable SP HIV-RNA was achieved in similar proportions between the two regimens at each timepoint. Overall, eight patients still presented detectable HIV-RNA or HIV-DNA in semen at W48; 15.4% and 28.6% presented detectable HIV-RNA and 9.1% and 14.3% presented detectable HIV-DNA in dolutegravir- and darunavir-based cART groups, respectively, with no significant difference. Conclusions For the first time, to the best of our knowledge, we showed that a dolutegravir-based regimen initiated as soon as PHI reduces HIV-RNA and HIV-DNA with no difference compared with a control group receiving a darunavir-based regimen. Although the viral purge in semen seems longer after treatment in PHI than CHI, due to high viral loads, early dolutegravir-based treatment initiation permits a major decay of both viral particles and infected cells in semen, efficiently reducing the high risk of transmission during PHI.

Published
2021

16. Becoming adherent to a preventive treatment for HIV: a qualitative approach

Author

Claire Pintado, Eric Cua, Julie Chas, Costanza Puppo, Bruno Spire, Marie Suzan-Monti, Vanessa Laguette, Jean-Michel Molina, Xavier Mabire, Daniela Rojas Castro, Marie Préau, Stéphane Morel, Hôpital l'Archet, Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Groupe de Recherche en Psychologie Sociale (GRePS), Université Lumière - Lyon 2 (UL2), AIDES Association [France], Centre de Recherche en Psychologie : Cognition, Psychisme et Organisations - UR UPJV 7273 (CRP-CPO), Université de Picardie Jules Verne (UPJV), Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U1252 INSERM - Aix Marseille Univ - UMR 259 IRD), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Coalition PLUS [Pantin, France], CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Universitaire de Nice (CHU Nice), Service de maladies infectieuses et tropicales [Saint-Louis], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], ANRS (France Recherche Nord & Sud Sida-HIV Hépatites) and funded by the ANRS and the Fonds de dotation Pierre Bergé pour la Prévention – SIDACTION, Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], and HAL AMU, Administrateur

Subjects
Adult, Male, medicine.medical_specialty, Anti-HIV Agents, Human immunodeficiency virus (HIV), HIV Infections, coping strategies, medicine.disease_cause, Medication Adherence, 03 medical and health sciences, 0302 clinical medicine, Double-Blind Method, prevention, stigmatization, On demand, medicine, Humans, adherence, 030212 general & internal medicine, PrEP intake, Qualitative Research, ComputingMilieux_MISCELLANEOUS, Applied Psychology, 030505 public health, business.industry, HIV, Focus Groups, 3. Good health, Clinical trial, Psychiatry and Mental health, Clinical Psychology, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Family medicine, Pre-Exposure Prophylaxis, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, 0305 other medical science, business, qualitative methods, Qualitative research
Abstract

The clinical trial ANRS-IPERGAY investigated the efficacy of sexual activity-based (i.e. on demand) HIV pre-exposure prophylaxis (PrEP). Using a qualitative method, we analysed the role of adherence as one of the main elements for PrEP effectiveness and its associated determinants. Data were collected in various French ANRS-IPERGAY sites during the double-blind (2012-2014) and open-label study (2015-2016) phases, through two individual interviews per participant, collective interviews and focus groups. A total of 83 participants participated in the present study. Our analysis included 32 individual interviews (with 16 participants), 13 collective interviews (

Published
2019
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17. Inflammatory Markers During Early Treatment of Seroconverters in a Randomized Placebo-Controlled Trial of PrEP (ANRS-IPERGAY)

Author

Jean-Michel Molina, Sylvain Chawki, Diane Carette, Claire Pintado, Laurence Meyer, Laurent Cotte, Isabelle Charreau, Audrey Gabassi, Marie-Laure Chaix, Constance Delaugerre, Gilles Pialoux, Eric Cua, Laboratoire de Virologie [CHU Saint-Louis], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Génomes, biologie cellulaire et thérapeutiques (GenCellDi (U944 / UMR7212)), Collège de France (CdF (institution))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Archet 2 [Nice] (CHU), Service de Maladies Infectieuses et Tropicales [Hôpital de la Croix-Rousse - HCL], Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Service de Maladies infectieuses et tropicales [CHU Tenon], CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de maladies infectieuses et tropicales [Saint-Louis], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPCité), Gestionnaire, Hal Sorbonne Université, Génomes, biologie cellulaire et thérapeutiques (GenCellDi (UMR_S_944)), Collège de France (CdF (institution))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Service des maladies infectieuses et tropicales [CHU Tenon], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université de Paris (UP)

Subjects
medicine.medical_specialty, [SDV]Life Sciences [q-bio], Placebo-controlled study, Human immunodeficiency virus (HIV), D-dimers, Inflammation, 030204 cardiovascular system & hematology, medicine.disease_cause, Early initiation, 03 medical and health sciences, Pre-exposure prophylaxis, 0302 clinical medicine, Internal medicine, medicine, 030212 general & internal medicine, Interleukin 6, biology, business.industry, HIV, sCD14, Antiretroviral therapy, Inflammatory biomarkers, IL6, PrEP, 3. Good health, [SDV] Life Sciences [q-bio], Infectious Diseases, AcademicSubjects/MED00290, Oncology, biology.protein, Brief Reports, medicine.symptom, early antiretroviral therapy, business, CRP
Abstract

HIV-related inflammation is associated with poor outcomes. We describe inflammatory biomarkers in 17 participants in a pre-exposure prophylaxis trial who seroconverted with very early initiation of antiretroviral therapy. Inflammation peaked at the time of HIV infection and returned to baseline within 6–12 months. Starting antiretroviral therapy very early could help mitigate long-lasting HIV-related inflammation., In seventeen HIV-seroconverters in a PrEP trial who were treated very early on, inflammation peaked at the time of HIV-infection and returned to pre-HIV-infection levels within twelve months. Starting antiretroviral therapy very early could help mitigate long-lasting HIV-related inflammation.

Published
2021
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18. Opportunités manquées de PrEP en France en 2019 : Enquête ANRS 95041

Author

I. Poizot-Martin, Bruno Spire, G. Pialoux, Hélène Laroche, M. Preau, Laurent Cotte, Eric Cua, A. Chéret, L. Piroth, and Caroline Lions

Subjects
Infectious Diseases
Abstract

Introduction La prophylaxie pre exposition (PrEP) est un outil de prevention qui cible les personnes a risque de contamination par le VIH. A ce jour, aucune information n’est disponible concernant la proportion de personnes qui auraient pu beneficier de la PrEP en France parmi les personnes nouvellement infectees. Materiels et methodes Enquete nationale multicentrique proposee entre 04/2019 et 10/2020 aux personnes presentant une infection recente au VIH definie par un test serologique incomplet ou un antecedent de test negatif dans les 6 derniers mois. Les circonstances de decouverte, pratiques a risque, antecedents d’infections sexuellement transmissibles (IST), le niveau de connaissance vis a vis de la PrEP ainsi que le niveau scolaire et social ont ete recueillis par auto-questionnaire (AQ). Resultats Parmi les 224 infections recentes diagnostiquees, 185 AQ ont ete renseignes. Ce sont majoritairement des hommes (n = 177, 96 %), d’âge median 33 [27-46] ans, nes en France metropolitaine (n = 132, 72 %), avec un niveau scolaire bac (n = 151, 82,5 %), vivant dans une grande ville ou en peripherie (n = 151, 82 %) et satisfaits de leur situation financiere (n = 119, 64 %). Le mode de contamination est heterosexuel pour les 8 femmes (âge median = 40 [28-45] ans), et chez les hommes, 149 (80,5 %) sont des hommes ayant des relations sexuelles avec des hommes (HSH) (âge median: 32 [27-44] ans), 18 ont ete contamines par relations sexuelles avec une femme (âge median: 46 [32-55] ans), 2 par usage de drogues, 2 suite a un accident d’exposition a risque viral, et est indetermine pour 6. Une activite de chemsex est rapportee chez 37 % (n = 68). Selon les recommandations francaises de 2018, 168 (90,81 %) presentaient une indication de Prep: 163 HSH, 2 transgenres, 13 en situation de prostitution, 13 avaient un partenaire positif au VIH et 17 etaient des usagers de drogues par voie intraveineuse, certains pouvant cumuler plusieurs criteres. Parmi les 168, 152 (90 %) ont vu au moins une fois un medecin l’annee precedant le diagnostic, majoritairement un medecin generaliste (85 %), 107 (64 %) ont discute de prevention, 43 (26 %) ont recu une information sur la PrEP, 26 (15 %) se l’ont vu proposer et 9 (5 %) l’ont prise. La non connaissance de la PrEP ou de ses modalites, des pratiques considerees non a risque, la peur des effets secondaires, l’absence de proposition de PrEP, sont les raisons les plus frequentes a la non prise de PrEP pour respectivement 45 (24 %), 24 (20 %), 40 (33 %), 34 (28 %), 29 (24 %) patients. Conclusion La PrEP etait indiquee dans pres de 90% des cas. La cascade de prise de PrEP met en evidence 2 defaillances majeures: une insuffisance d’information delivree par les soignants et son acceptation chez les patients informes et concernes. Ces premiers resultats soulignent la necessite d’etendre la primo-prescription de la PrEP aux medecins de premier recours.

Published
2021
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19. Incidence of diabetes in HIV-infected patients treated with first-line integrase strand transfer inhibitors: a French multicentre retrospective study

Author

P Fischer, C Aumeran, V Ronat, L Laine, S Bouchez, André Cabié, D Lambert, Eric Cua, J Pasquier, F Touam, Laurent Hocqueloux, A Maillard, O Deradji, Charlotte Charpentier, Véronique Avettand-Fenoel, Catherine Tamalet, Anne Frésard, Elodie Curlier, M Batard, S Ferrando, S Breaud, Philippe Bossi, C Pronier, C Gubavu, M Martin-Degiovani, Samira Fafi-Kremer, A. Duréault, Christian Pradier, A Montoya Ferrer, M Piffaut, Faiza Ajana, V Rio, A Maka, C Biron, Pierre Delobel, A de Monte, P Choisy, L Lelièvre, K Risso, N. Viget, Q Lepiller, Véronique Reliquet, I Perbost, Laurence Bocket, C Rioux, G Thomas, O. Aubry, L. Porte, Cédric Arvieux, Thomas Jovelin, Elisabeth Botelho-Nevers, Pierre-Marie Roger, C Etienne, David Boutoille, S Le Gac, Caroline Charlier, Virginie Ferré, M Pradier, M C Receveur, Isabelle Ravaux, Philippe Colson, K Rome, O Lesens, C Brunet-Cartier, A Meybeck, Romain Palich, P Martinet, V. Le Moing, C Ceppi, Hélène Laroche, I Lamaury, V Brodard, N Oran, M Lefebvre, P Morineau, K Guitteaud, M Bistoquet, Diane Descamps, O Cabras, Amandine Gagneux-Brunon, Brigitte Montes, Olivier Robineau, I Jaquet, Roland Landman, C Cheneau, V Mondain, Caroline Lions, Olivier Grossi, Laurent Boyer, C Debreux, M André, A Rodallec, Philippe Van de Perre, Jade Ghosn, Clotilde Allavena, Sylvie Abel, Karine Sauné, F Louni, F Boulard, Luminita Schneider, Dominique Merrien, D Chirio, S Pillet, Mathieu Dupont, A Motte, F Lemaitre, C Guennoun, Benoît Henry, S Sausse, Michel Vidal, M Mokhtari, O Zaegel-Faucher, Eric Rosenthal, Isabelle Poizot-Martin, Faouzi Souala, Matthieu Revest, M Baldeyrou, S Patrat-Delon, Jacques Reynes, M Cavellec, Laurent Cotte, C Michelangeli, François Danion, M Priester, Axel Ursenbach, C Mackoumbou-Nkouka, Thomas Perpoint, A Cheret, P Geneau de Lamarlière, Christian Rabaud, Agathe Becker, Tristan Ferry, A. Ivanova, Elina Teicher, T Bonijoly, F-Xavier Lescure, O Bollangier, A S Ritleng, Patrick Miailhes, A Gervais, Y N’guyen, Patrice Muret, Elisa Demonchy, Vincent Max, I Alcaraz, N Meftah, M P Bouillon, S Degroodt, A Foltzer, Laurent Hustache-Mathieu, Jean-Luc Berger, A Ménard, J Prouteau, B. Bonnet, Kevin Bouiller, Lise Cuzin, Christian Chidiac, R Agher, S Leautez, Catherine Chirouze, M Poinot, R Tubiana, E Aïssi, O Babre, J Lourenco, Benoit Tressières, C Clavel, Cécile Goujard, A Brunet, Claire Triffault-Fillit, F Raffi, E Sidani, Anne-Sophie Brunel, A Madrid, B Prouvost-Keller, Eric Delaporte, M J Soavi, J. M. Chapplain, M Orticoni, Pascal Pugliese, V Corbin, Pierre Tattevin, C Boulard, Véronique Obry-Roguet, P. Loubet, Paul-Henri Consigny, Elisabeth André-Garnier, J Sinteff, S Lariven, A Boucher, N Lerolle, C Blanc, Y Quertainmont, Sylvie Bregigeon, Bruno Hoen, André Boibieux, S Casanova, N Atoui, C Dhiver, N Biezunski, R Ouissa, M. Hentzien, C Bernard-Henry, Sophie Matheron, Cécile Herrmann-Storck, Firouzé Bani-Sadr, I Touitou, Eric Billaud, I Kmiec, Benoit Pilmis, T Prazuck, Romain Guery, Karima Amazzough, C Merle de Boever, Marine Morrier, T Guimard, M Poisson-Vanier, H Laurichesse, Catherine Varache, J Goesch, Guillaume Martin-Blondel, Z Julia, M Ducassou, F. Lucht, B Lafon-Desmurs, Martine Valette, A Sève, Marc-Antoine Valantin, G Zouzou, A Barrail-Tran, M Delestan, M. Alvarez, A Naqvi, Colin Deschanvres, A Raoux, L Meddeb, Rodolphe Garraffo, C Daniel, T May, A. Galinier, François Bénézit, Yazdan Yazdanpanah, Veronique Joly, Olivier Lortholary, C Louisin, K Jidar, I Fabre, Cyrille Delpierre, Christine Katlama, P Parize, S Galie, Claudine Duvivier, P. Dellamonica, L Osei, C Drobacheff-Thiébaut, Sandrine Pierre-François, G Cessot, C. Tomei, F. Biron, Christine Jacomet, G Benabdelmoumen, Florence Ader, David Rey, Marialuisa Partisani, J Turmel, J. Durant, S Seang, F. Bozon, M Illiaquer, N Hall, Edouard Tuaillon, S. Roux, Florent Valour, A. Belkhir, Marine Maurel, V Baclet, N Mrozek, Olivier Baud, S Sécher, P Letertre-Gibert, Alexa Debard, E de Mautort, Fanny Lanternier, Alain Makinson, H. Tissot Dupont, P Lansalot, E Ressiot, T. Huleux, S Wehrlen-Pugliese, M Landon, C Brochier, C Bernaud, Gilles Peytavin, A Soria, Institut Hospitalier Universitaire Méditerranée Infection (IHU Marseille), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques er émergentes (TransVIHMI), Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Institut de Recherche pour le Développement (IRD)-Université de Yaoundé I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Université Montpellier 1 (UM1), Département Maladies Infectieuses et Tropicales, Hôpital Universitaire, Montpellier, France, Pathogénèse et contrôle des infections chroniques (PCCI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre Hospitalier Universitaire de Montpellier (CHU Montpellier ), Service de pharmacologie, Hôpital Pasteur [Nice] (CHU)-Centre Hospitalier Universitaire de Nice (CHU Nice), Centre Hospitalier Universitaire de Reims (CHU Reims), Laboratoire de Virologie Médicale et Moléculaire - EA 4684 (CardioVir), Université de Reims Champagne-Ardenne (URCA)-SFR CAP Santé (Champagne-Ardenne Picardie Santé), Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Centre Hospitalier Universitaire de Reims (CHU Reims), Groupe Immunité des Muqueuses et Agents Pathogènes (GIMAP), Université Jean Monnet [Saint-Étienne] (UJM), School of Civil and Environmental Engineering [Sydney], University of New South Wales [Sydney] (UNSW), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Laboratoire Chrono-environnement - CNRS - UFC (UMR 6249) (LCE), Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon), Pathologies Pulmonaires et Plasticité Cellulaire - UMR-S 1250 (P3CELL), and Université de Reims Champagne-Ardenne (URCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
0301 basic medicine, Microbiology (medical), Adult, medicine.medical_specialty, [SDV]Life Sciences [q-bio], Integrase inhibitor, HIV Infections, HIV Integrase, Diabetes Therapy, Cohort Studies, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Internal medicine, Diabetes mellitus, medicine, Diabetes Mellitus, Humans, Pharmacology (medical), 030212 general & internal medicine, HIV Integrase Inhibitors, ComputingMilieux_MISCELLANEOUS, Retrospective Studies, Pharmacology, Integrases, business.industry, Incidence, Retrospective cohort study, Raltegravir, medicine.disease, Comorbidity, 3. Good health, 030104 developmental biology, Infectious Diseases, chemistry, Dolutegravir, business, medicine.drug, Cohort study
Abstract

BackgroundIntegrase strand transfer inhibitors (INSTIs) are increasingly used in patients living with HIV due to their safety, effectiveness and high genetic barrier. However, an association with weight gain has recently been suggested and several cases of diabetes mellitus have been reported with raltegravir and dolutegravir. The long-time metabolic impact of these recent molecules remains unclear.ObjectivesTo assess if an INSTI as a third agent is statistically associated with new-onset diabetes mellitus compared with an NNRTI or a PI.Patients and methodsPatients undergoing first-line combined ART (cART) without diabetes at baseline were retrospectively included from the Dat’AIDS French cohort study (ClinicalTrials.gov NCT02898987). Incident diabetes mellitus was defined as a notification of new diabetes in the medical history, a glycated haemoglobin (HbA1c) level superior to 7.5% or the start of a diabetes therapy following the initiation of ART.ResultsFrom 2009 to 2017, 19 462 patients were included, among which 265 cases of diabetes mellitus occurred. Multivariate and survival analyses did not highlight an increase in new-onset diabetes in patients undergoing cART with an INSTI as a third agent compared with an NNRTI or a PI. BMI >30 kg/m2, age >37 years old (in survival analysis), black race or Hispanic ethnicity, arterial hypertension and AIDS were associated with a higher proportion of incident diabetes.ConclusionsINSTIs were not statistically associated with new-onset diabetes. However, clinicians should remain aware of this possible metabolic comorbidity, particularly in patients with a high BMI and older patients.

Published
2020
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20. High Prevalence of Acquired Thrombophilia Without Prognosis Value in Patients With Coronavirus Disease 2019

Author

Denis Doyen, Anny Appert-Flory, V. Mondain, Emile Ferrari, Jacques Levraut, David Chirio, Pierre Toulon, Florence Fischer, Carole Ichai, Mohamed Labbaoui, Julie Contenti, Fabien Lemoel, Jean Dellamonica, Pamela Moceri, Benjamin Sartre, Baptiste Mossaz, Eric Cua, Fabien Squara, Jean Christophe Orban, Céline Occelli, K. Risso, Hôpital Pasteur [Nice] (CHU), Université Nice Sophia Antipolis - Faculté de Médecine (UNS UFR Médecine), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA), Centre Hospitalier Universitaire de Nice (CHU Nice), Service de Réanimation médico-chirurgicale [Nice], Hôpital Saint-Roch [Nice], Centre méditerranéen de médecine moléculaire (C3M), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'infectiologie [CHU Nice], Gestionnaire, HAL Sorbonne Université 5, Université Nice Sophia Antipolis (1965 - 2019) (UNS), and COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA)

Subjects
Male, Disease, 030204 cardiovascular system & hematology, Severity of Illness Index, Vascular Medicine, Protein S, 0302 clinical medicine, Risk Factors, Clinical Studies, Prevalence, Original Research, Lupus anticoagulant, medicine.diagnostic_test, biology, Middle Aged, Antiphospholipid Syndrome, Prognosis, Thrombosis, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, 3. Good health, Antibodies, Antiphospholipid, Female, France, Cardiology and Cardiovascular Medicine, Coronavirus Infections, Partial thromboplastin time, medicine.medical_specialty, Protein S Deficiency, Pneumonia, Viral, Thrombophilia, 03 medical and health sciences, coronavirus disease 2019, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Vascular Biology, Internal medicine, Severity of illness, medicine, Humans, Pathological, Pandemics, thrombosis, Aged, thrombophilia, 030203 arthritis & rheumatology, business.industry, COVID-19, medicine.disease, biology.protein, business, Biomarkers
Abstract

Background Recent literature reports a strong thrombotic tendency in patients hospitalized for a coronavirus disease 2019 (COVID‐19) infection. This characteristic is unusual and seems specific to COVID‐19 infections, especially in their severe form. Viral infections can trigger acquired thrombophilia, which can then lead to thrombotic complications. We investigate for the presence of acquired thrombophilia, which could participate in this phenomenon, and report its prevalence. We also wonder if these thrombophilias participate in the bad prognosis of severe COVID‐19 infections. Methods and Results In 89 consecutive patients hospitalized for COVID‐19 infection, we found a 20% prevalence of PS (protein S) deficiency and a high (ie, 72%) prevalence of antiphospholipid antibodies: mainly lupus anticoagulant. The presence of PS deficiency or antiphospholipid antibodies was not linked with a prolonged activated partial thromboplastin time nor with D‐dimer, fibrinogen, or CRP (C‐reactive protein) concentrations. These coagulation abnormalities are also not linked with thrombotic clinical events occurring during hospitalization nor with mortality. Conclusions We assess a high prevalence of positive tests detecting thrombophilia in COVID‐19 infections. However, in our series, these acquired thrombophilias are not correlated with the severity of the disease nor with the occurrence of thrombotic events. Albeit the strong thrombotic tendency in COVID‐19 infections, the presence of frequent acquired thrombophilia may be part of the inflammation storm of COVID‐19 and should not systematically modify our strategy on prophylactic anticoagulant treatment, which is already revised upwards in this pathological condition. Registration URL: https://www.clini​caltr​ials.gov ; Unique identifier: NCT04335162.

Published
2020
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21. Evaluation of Drug Abuse by Hair Analysis and Self-Reported Use Among MSM Under PrEP: Results From a French Substudy of the ANRS-IPERGAY Trial

Author

Jean-Michel Molina, Islam Amine Larabi, Laurent Cotte, Catherine Capitant, Eric Cua, Jean-Claude Alvarez, Julie Chas, François Raffi, Armelle Pasquet, Gilles Pialoux, Gilles Peytavin, Bruno Spire, Rebecca Bauer, Perrine Roux, Laurence Meyer, CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital Raymond Poincaré [AP-HP], Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U1252 INSERM - Aix Marseille Univ - UMR 259 IRD), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Observatoire régional de la santé Provence-Alpes-Côte d'Azur [Marseille] (ORS PACA), Service d'infectiologie [CHU Nice], Centre Hospitalier Universitaire de Nice (CHU Nice), Service de Maladies Infectieuses et Tropicales [Hôpital de la Croix-Rousse - HCL], Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Service des Maladies Infectieuses et Tropicales [Hôpital Gustave Dron, Tourcoing], Centre Hospitalier Gustave Dron [Tourcoing], Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)

Subjects
Drug, Adult, Male, medicine.medical_specialty, Anti-HIV Agents, Substance-Related Disorders, media_common.quotation_subject, Sexual Behavior, Ecstasy, Sexually Transmitted Diseases, HIV Infections, 030312 virology, Men who have sex with men, Drug detection, 03 medical and health sciences, Sexual and Gender Minorities, Internal medicine, Surveys and Questionnaires, Prevalence, Medicine, Humans, Pharmacology (medical), Homosexuality, Male, Sida, media_common, 0303 health sciences, Harm reduction, biology, Unsafe Sex, business.industry, Hair analysis, medicine.disease, biology.organism_classification, Substance abuse, Infectious Diseases, Sexual Partners, Hair Analysis, Pre-Exposure Prophylaxis, Self Report, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

BACKGROUND We used the Agence nationale de Recherches sur le sida et les hepatites virales (ANRS)-IPERGAY trial to qualitatively and quantitatively measure drug use among men who have sex with men under preexposure prophylaxis using 2 different methods, to better understand and collectively respond to risky practices. METHOD We included 69 volunteers of the ANRS-IPERGAY trial. We measured drug use by 2 methods: (1) drug detection by hair analysis and (2) reported drug use by self-reported drug consumption. RESULTS New psychoactive substances (NPS) and conventional drugs were detected in 53 of the 69 (77%) volunteers by hair analysis and in 39 of the 69 (57%) volunteers by questionnaires. On the 219 hair segments analyzed, the most commonly used drugs were cocaine in 47 of the 69 (68%), 3,4-methylenedioxymethamphetamine/ecstasy in 31 of the 69 (45%), and NPS in 27 of the 69 (39%). On the 1061 collected questionnaires, the most commonly used drugs were cocaine in 31 of the 69 (45%), 3,4-methylenedioxymethamphetamine/ecstasy in 29 of the 69 (42%), and NPS in 16 of the 69 (23%). Hair analysis detects more conventional drugs and/or NPS use (P < 0.05). Drug use identified by hair was significantly associated with a higher number of sexual partners in the past 2 months (P ≤ 0.001), more often casual partners (P ≤ 0.001), condomless anal sex (P ≤ 0.005), hardcore sexual practices (P ≤ 0.001), a higher number of sexually transmitted infections, and chemsex (P ≤ 0.05). CONCLUSIONS Self-report drug use by questionnaires remains the reference tool for harm reduction at the individual level because of its feasibility and low cost. However, hair analysis is more sensitive, objectively assessing consumption, and interesting to understand uses and to be able to collectively respond to risky practices with adapted messages.

Published
2020
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22. Functional Exhaustion of Type I and II Interferons Production in Severe COVID-19 Patients

Author

Caroline Ruetsch, Vesna Brglez, Marion Crémoni, Kévin Zorzi, Céline Fernandez, Sonia Boyer-Suavet, Sylvia Benzaken, Elisa Demonchy, Karine Risso, Johan Courjon, Eric Cua, Carole Ichai, Jean Dellamonica, Thierry Passeron, and Barbara Seitz-Polski

Subjects
0301 basic medicine, 2019-20 coronavirus outbreak, lcsh:R5-920, Coronavirus disease 2019 (COVID-19), business.industry, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), COVID-19, General Medicine, interferon, personalized medicine, infectious diseases, Virology, immunology, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Interferon, 030220 oncology & carcinogenesis, medicine, Medicine, Personalized medicine, business, lcsh:Medicine (General), Original Research, medicine.drug
Abstract

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has emerged in Wuhan in December 2019 and has since spread across the world. Even though the majority of patients remain completely asymptomatic, some develop severe systemic complications. In this prospective study we compared the immunological profile of 101 COVID-19 patients with either mild, moderate or severe form of the disease according to the WHO classification, as well as of 50 healthy subjects, in order to identify functional immune factors independently associated with severe forms of COVID-19. Plasma cytokine levels, and cytokine levels upon in vitro non-specific stimulation of innate and adaptive immune cells, were measured at several time points during the course of the disease. As described previously, inflammatory cytokines IL1β, IL6, IL8, and TNFα associated with cytokine storm were significantly increased in the plasma of moderate and severe COVID-19 patients (p < 0.0001 for all cytokines). During follow-up, plasma IL6 levels decreased between the moment of admission to the hospital and at the last observation carried forward for patients with favorable outcome (p = 0.02148). After in vitro stimulation of immune cells from COVID-19 patients, reduced levels of both type I and type II interferons (IFNs) upon in vitro stimulation were correlated with increased disease severity [type I IFN (IFNα): p > 0.0001 mild vs. moderate and severe; type II IFN (IFNγ): p = 0.0002 mild vs. moderate and p < 0.0001 mild vs. severe] suggesting a functional exhaustion of IFNs production. Stimulated IFNα levels lower than 2.1 pg/ml and IFNγ levels lower than 15 IU/mL at admission to the hospital were associated with more complications during hospitalization (p = 0.0098 and p =0.0002, respectively). A low IFNγ level was also confirmed by multivariable analysis [p = 0.0349 OR = 0.98 (0.962; 0.999)] as an independent factor of complications. In vitro treatment with type IFNα restored type IFNγ secretion in COVID-19 patients while the secretion of pro-inflammatory cytokines IL6 and IL1β remained stable or decreased, respectively. These results (a) demonstrate a functional exhaustion of both innate and adaptive immune response in severe forms of COVID-19; (b) identify IFNα and IFNγ as new potential biomarkers of severity; and (c) highlight the importance of targeting IFNs when considering COVID-19 treatment in order to re-establish a normal balance between inflammatory and Th1 effector cytokines.

Published
2020

23. Reaching the Second and Third Joint United Nations Programme on Human Immunodeficiency Virus (HIV)/AIDS 90-90-90 Targets Is Accompanied by a Dramatic Reduction in Primary HIV Infection and in Recent HIV Infections in a Large French Nationwide HIV Cohort

Author

Claudine Duvivier, Clotilde Allavena, J Lippmann, P. Dellamonica, A Soria, Sandrine Pierre-François, B J Gaborit, Isabelle Poizot-Martin, Anne Frésard, Elodie Curlier, F. Biron, Eric Cua, M Saadia Mokhtari, I Luquet Besson, C Gubavu, Caroline Lions, Laurent Cotte, C. Tomei, Elina Teicher, Faouzi Souala, Karima Amazzough, C Merle de Boever, Romain Palich, C Brochier, Véronique Reliquet, Patrick Miailhes, M Priester, Samira Fafi-Kremer, Mathieu Dupont, M Piffaut, I. Schlienger, C Bernaud, A S Ritleng, F-Xavier Lescure, C Cheneau, L Lelièvre, C Biron, Adrien Le Guillou, Alexa Debard, Marc-Antoine Valantin, Gilles Peytavin, S Lariven, G Benabdelmoumen, Florence Ader, I Kmiec, I Fabre, Cyrille Delpierre, C. Longuet, François Raffi, A de Monte, M. Alvarez, David Rey, A Boucher, M. Valette, E de Mautort, Jean-Luc Berger, H Bertone, Bruno Hoen, M Poisson-Vanier, Pascal Pugliese, Virginie Ferré, M Pradier, Z Julia, Nathalie Dournon, M Baldeyrou, N Biezunski, Caroline Charlier, J Goesch, J Pasquier, M P Bouillon, Cécile Goujard, Sophie Matheron, V. Le Moing, Romain Guery, N. Viget, N Atoui, C Dhiver, A Meybeck, Fanny Lanternier, F Touam, Tristan Ferry, M Carta Padovani, G Thomas, C Ceppi, A Brunet, Alain Makinson, Isabelle Ravaux, Laurent Hocqueloux, A Maillard, Firouzé Bani-Sadr, P. Loubet, Laurent Boyer, O Deradji, I Alcaraz, T Prazuck, A Rodallec, F Lemaitre, B Lafon-Desmurs, J Turmel, A Sève, Benoit Pilmis, A Gervais, C. Augustin-Normand, D Chirio, Brigitte Montes, Cédric Arvieux, V Brodard, M Delestan, E Aïssi, C Louisin, Christian Chidiac, M Ducassou, S Leautez, Catherine Chirouze, M André, Dominique Merrien, Q Gardiennet, P Fischer, Sylvie Abel, Guillaume Martin-Blondel, Benoît Henry, H. Tissot Dupont, S Patrat-Delon, A Ménard, E. Billaud, Malikhone Chansombat, K Jidar, Karine Sauné, Colin Deschanvres, V. Gueripel, M Cavellec, K. Schepers, C Pronier, R Ouissa, P Choisy, A Cheret, A. Belkhir, P Parize, A Barrail-Tran, B. Bonnet, C Mackoumbou-Nkouka, A. Galinier, M Monclar, P Lansalot, S Bouchez, C Guennoun, N Meftah, C Brunet-Cartier, Pierre Tattevin, J. Durant, E Ressiot, T. Huleux, François Bénézit, C Boulard, M Poinot, Elisabeth André-Garnier, J Sinteff, André Cabié, Charlotte Charpentier, L Meddeb, Rodolphe Garraffo, M Batard, D. Lebrun, R Tubiana, M J Soavi, I Lamaury, Philippe Bossi, Y Quertainmont, S Galie, C Michelangeli, François Danion, N Lerolle, Y N’guyen, Amandine Gagneux-Brunon, Elisa Demonchy, Christine Katlama, C Bernard-Henry, V Mondain, S Seang, David Boutoille, P. Le Turnier, Faiza Ajana, André Boibieux, J Koffi, L. Porte, Laurence Bocket, O Bollangier, A Maka, S Sécher, Marine Morrier, T Guimard, Matthieu Revest, C Godard, C Rioux, C Etienne, M Illiaquer, O. Aubry, N Hall, Paul-Henri Consigny, C Blanc, P Morineau, K Guitteaud, T. Perpoint, G Cessot, V Baclet, Lise Cuzin, T May, E Braun, Marialuisa Partisani, Veronique Joly, Jacques Reynes, Olivier Lortholary, C Blanco-Betancourt, Philippe Van de Perre, D Lambert, Moustapha Dramé, S Ferrando, S Breaud, A Montoya Ferrer, Yazdan Yazdanpanah, M. Hentzien, Cécile Herrmann-Storck, A. Duréault, A. Ivanova, F. Lucht, Pierre Delobel, Thomas Jovelin, J. M. Chapplain, Olivier Robineau, Roland Landman, Olivier Grossi, F Louni, Elisabeth Botelho-Nevers, J Lourenco, M Lefebvre, Diane Descamps, Luminita Schneider, R Agher, M Orticoni, D Rahli, S Degroodt, CHU de la Martinique [Fort de France], Centre Hospitalier Universitaire de Nice (CHU Nice), Service de maladies infectieuses et tropicales [Nantes], Université de Nantes (UN)-Hôtel-Dieu-Centre hospitalier universitaire de Nantes (CHU Nantes), Department of Infectious Diseases [Nantes], Hôtel-Dieu de Nantes, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Infectious Diseases and Tropical Medicine Unit [Fort-de-France, Martinique], Centre Hospitalier Universitaire de Reims (CHU Reims), Laboratoire de Virologie Médicale et Moléculaire - EA 4684 (CardioVir), Université de Reims Champagne-Ardenne (URCA)-Centre Hospitalier Universitaire de Reims (CHU Reims)-SFR CAP Santé (Champagne-Ardenne Picardie Santé), Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV), Département de maladies infectieuses, and Hospices Civils de Lyon (HCL)

Subjects
0301 basic medicine, Microbiology (medical), Cart, medicine.medical_specialty, Longitudinal study, business.industry, Public health, Incidence (epidemiology), medicine.disease, 030112 virology, 3. Good health, 03 medical and health sciences, 0302 clinical medicine, Infectious Diseases, Acquired immunodeficiency syndrome (AIDS), Interquartile range, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Internal medicine, Epidemiology, Cohort, Medicine, 030212 general & internal medicine, business
Abstract

Background In late 2013, France was one of the first countries to recommend initiation of combination antiretroviral therapy (cART) irrespective of CD4 cell count. Methods To assess the impact of achieving the second and third Joint United Nations Programme on HIV/AIDS 90-90-90 targets (ie, 90% of diagnosed people on sustained cART, and, of those, 90% virologically controlled) on human immunodeficiency virus (HIV) incidence, we conducted a longitudinal study to describe the epidemiology of primary HIV infection (PHI) and/or recent HIV infection (patients with CD4 cell count ≥500/mm3 at HIV diagnosis; (PRHI) between 2007 and 2017 in a large French multicenter cohort. To identify changes in trends in PHI and PRHI, we used single breakpoint linear segmented regression analysis. Results During the study period, 61 822 patients were followed in the Dat’AIDS cohort; 2027 (10.0%) had PHI and 7314 (36.1%) had PRHI. The second and third targets were reached in 2014 and 2013, respectively. The median delay between HIV diagnosis and cART initiation decreased from 9.07 (interquartile range [IQR], 1.39–33.47) months in 2007 to 0.77 (IQR, 0.37–1.60) months in 2017. A decrease in PHI (−35.1%) and PRHI (−25.4%) was observed starting in 2013. The breakpoints for PHI and PRHI were 2012.6 (95% confidence interval [CI], 2010.8–2014.4) and 2013.1 (95% CI, 2011.3–2014.8), respectively. Conclusions Our findings show that the achievements of 2 public health targets in France and the early initiation of cART were accompanied by a reduction of about one-third in PHI and PRHI between 2013 and 2017. Clinical Trials Registration NCT02898987.

Published
2020
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24. Coverage of Sex Acts by Event-Driven Pre-exposure Prophylaxis: A Sub-Study of the ANRS IPERGAY Trial

Author

Claire Pintado, Christian Chidiac, Gilles Pialoux, Julien Fonsart, Nicolas Etien, Laurence Meyer, Rebecca Bauer, Emmanuelle Netzer, Jean-Michel Molina, Catherine Capitant, Cédric Etienne, Eric Cua, and Véronique Doré

Subjects
Adult, Male, Social Psychology, Anti-HIV Agents, Sexual Behavior, HIV Infections, Full coverage, Medication Adherence, 03 medical and health sciences, Pre-exposure prophylaxis, 0302 clinical medicine, Double-Blind Method, Outcome Assessment, Health Care, Medicine, Humans, 030212 general & internal medicine, Homosexuality, Male, 030505 public health, Unsafe Sex, business.industry, Public Health, Environmental and Occupational Health, Monitoring system, Infectious Diseases, Sexual behavior, Pill, Pre-Exposure Prophylaxis, Open label, 0305 other medical science, business, Anal sex, Demography
Abstract

We assessed the coverage of sex acts by event-driven pre-exposure prophylaxis (ED-PrEP) over a 2-month period in 54 participants in the open label phase of the ANRS Ipergay trial. Participants received an electronic monitoring system device to record bottle openings. Self-questionnaires collected daily information on PrEP intake and sexual behavior. Intake was also estimated through returned pill counts. Full coverage of sex acts was defined as at least one pill taken both within 24 h before and within 48 h following sex. There was a strong correlation (r = − 0.92) between the number of bottle openings and returned pill counts. During the study, 42 participants (78%) practiced ED-PrEP and 12 (22%) daily PrEP with bottle openings at least 5 days/week whatever their sexual activity. Out of the 154 reported receptive anal sex acts, 81% were condomless: among them, PrEP coverage was hight: 97% among those practicing daily PrEP and 82% among those using ED-PrEP.

Published
2020

25. Medical table: A major tool for antimicrobial stewardship policy

Author

Pierre-Marie Roger, E. Leroux, K. Risso, Elisa Demonchy, S. Leroux, Eric Cua, and Johan Courjon

Subjects
0301 basic medicine, medicine.medical_specialty, business.industry, Health Policy, 030106 microbiology, Bacterial Infections, Anti-Bacterial Agents, Antimicrobial Stewardship, 03 medical and health sciences, 0302 clinical medicine, Infectious Diseases, Antibiotic resistance, Continuous evaluation, Intensive care, Practice Guidelines as Topic, Humans, Medicine, Antimicrobial stewardship, Table (database), 030212 general & internal medicine, business, Adverse effect, Intensive care medicine, Hospital stay, Health policy
Abstract

Infectious diseases are unpredictable, with heterogeneous clinical presentations, diverse pathogens, and various susceptibility rates to anti-infective agents. These features lead to a wide variety of clinical practices, which in turn strongly limits their evaluation. We have been using a medical table since 2005 to monitor the medical activity in our department. The observation of heterogeneous therapeutic practices led to drafting up our own antibiotic guidelines and to implementing a continuous evaluation of their observance and impact on morbidity and mortality associated with infectious diseases, including adverse effects of antibiotics, duration of hospital stay, use of intensive care, and deaths. The 10-year analysis of medical practices using the medical table is based on more than 10,000 hospitalizations. It shows simplified antibiotic therapies and a reduction in infection-related morbidity and mortality. The medical table is a major tool for antimicrobial stewardship, leading to constant benefits for patients.

Published
2017
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26. Prevalence and Incidence of Human Papillomavirus Infection in Men Having Sex With Men Enrolled in a Pre-exposure Prophylaxis Study: A Sub-study of the Agence Nationale de Recherches sur le SIDA et les Hépatites Virales 'Intervention Préventive de l'Exposition aux Risques avec et pour les hommes Gays' Trial

Author

Julien Puech, Jean-Michel Molina, Diane Carette, Hélène Péré, Constance Delaugerre, David Veyer, Cécile Tremblay, Christian Chidiac, Sébastien Fouéré, Isabelle Heard, Laurent Cotte, Isabelle Charreau, Eric Cua, Julie Chas, Jean-François Fléjou, Catherine Capitant, and Laurence Meyer

Subjects
Microbiology (medical), Male, medicine.medical_specialty, Anal Canal, HIV Infections, Men who have sex with men, 03 medical and health sciences, Pre-exposure prophylaxis, Sexual and Gender Minorities, 0302 clinical medicine, Cytology, medicine, Prevalence, Humans, 030212 general & internal medicine, Homosexuality, Male, Sida, Genotyping, Papillomaviridae, Gynecology, biology, business.industry, Incidence (epidemiology), Incidence, Papillomavirus Infections, HPV infection, virus diseases, Anus, biology.organism_classification, medicine.disease, Infectious Diseases, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Pre-Exposure Prophylaxis, business
Abstract

BackgroundHuman papillomavirus (HPV) infection is more frequent in men having sex with men (MSM) who are living with human immunodeficiency virus (HIV) than in MSM without HIV. There are currently no data regarding HPV infections in preexposure prophylaxis (PrEP)-using MSM.MethodsMSM living without HIV who were enrolled in the Agence Nationale de Recherches sur le SIDA et les Hépatites Virales "Intervention Préventive de l'Exposition aux Risques avec et pour les hommes Gays" PrEP study were prospectively enrolled. Anal, penile, and oral samples were collected at baseline and every 6 months for HPV detection and genotyping. Anal swabs for cytology were obtained at baseline and at 24 months.ResultsWe enrolled 162 participants. The prevalences of any HPV genotypes at baseline were 92%, 32%, and 12% at the anal, penile, and oral sites, respectively. High-risk (HR) HPV genotypes were observed in 84%, 25%, and 10% of anal, penile, and oral baseline samples, respectively. Nonavalent HPV vaccine genotypes were observed in 77%, 22%, and 6% of anal, penile, and oral baseline samples, respectively. Multiple infections were observed in 76%, 17%, and 3% of cases at the anal, penile, and oral sites, respectively. The most frequent HR genotypes were HPV 53, 51, and 16 in anal samples; HPV 33, 39, and 73 in penile samples; and HPV 66 in oral samples. The incidence of any HPV genotype at the anal site was 86.2/1000 person-months and the incidence of HR-HPV genotypes was 72.3/1000 person-months. The baseline cytology was normal in 32% of cases and was classified as atypical squamous cells of undetermined significance, low-grade squamous intra-epithelial lesion, high-grade squamous intra-epithelial lesion (HSIL), and atypical squamous cells that cannot exclude HSIL in 23%, 40%, 5%, and 1% of cases, respectively.ConclusionsPrEP users have a similar risk of HPV infection as MSM living with HIV and the risk is much higher than that previously reported in MSM living without HIV.

Published
2019

27. Changes in kidney function among men having sex with men starting on demand tenofovir disoproxil fumarate - emtricitabine for HIV pre-exposure prophylaxis

Author

Geoffroy Liegeon, Eric Cua, Cécile Tremblay, Catherine Capitant, Guillemette Antoni, Jean-Michel Molina, Laurent Cotte, Gilles Pialoux, Isabelle Charreau, Eric Senneville, Laurence Meyer, and François Raffi

Subjects
Adult, Male, medicine.medical_specialty, kidney, Tenofovir, Adolescent, Anti-HIV Agents, Urology, Renal function, HIV Infections, Emtricitabine, Placebo, 03 medical and health sciences, Pre-exposure prophylaxis, Sexual and Gender Minorities, Young Adult, 0302 clinical medicine, Double-Blind Method, On demand, medicine, eGFR, Humans, 030212 general & internal medicine, Research Articles, on‐demand, Kidney, 030505 public health, business.industry, Public Health, Environmental and Occupational Health, HIV, Middle Aged, PrEP, tenofovir, Infectious Diseases, medicine.anatomical_structure, intermittent, Pill, Female, Pre-Exposure Prophylaxis, 0305 other medical science, business, medicine.drug, Follow-Up Studies, Glomerular Filtration Rate, Research Article
Abstract

Introduction Daily pre‐exposure prophylaxis (PrEP) with tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) is associated with a small but statistically significant decrease in estimated glomerular filtration rate (eGFR). We assessed the renal safety of on‐demand PrEP with TDF/FTC in HIV‐1 uninfected men. Methods We used data from the randomized double‐blind placebo‐controlled ANRS‐IPERGAY trial and its open‐label extension conducted between February 2012 and June 2016 among HIV‐uninfected MSM starting on‐demand PrEP. Using linear mixed model, we evaluated the mean eGFR decline from baseline over time and determined risks factors associated with eGFR decline during the study. Results During the blind phase, with a median follow‐up of 9.4 months, the mean decline slope of eGFR from baseline was −0.88 and −1.53 mL/min/1.73 m2 per year in the placebo (n = 201) and the TDF/FTC group (n = 198) respectively, with a slope difference of 0.65 mL/min/1.73 m2 per year (p = 0.27). Including both phases, 389 participants started on‐demand TDF/FTC with a median follow‐up of 19.2 months and a mean decline of eGFR from baseline of −1.14 mL/min/1.73 m2 per year (p 40 years (p = 0.24) or hypertension (p = 0.21). There was a dose‐response relationship between recent tenofovir exposure and lower eGFR when considering the number of pills taken in the two months prior the visit (eGFR difference of −0.88 mL/min/1.73 m2 between >15 pills/month vs. ≤15 pills/month, p 2 to ≤10ng/mL: −0.98 mL/min/1.73 m2, >10 to ≤40ng/mL: −1.28 mL/min/1.73 m2, >40 ng/mL: −1.82 mL/min/1.73 m2, p

Published
2019

28. Community-Based Care in the ANRS-IPERGAY Trial: The Challenges of Combination Prevention

Author

Eric Cua, Costanza Puppo, Marie Préau, Laurent Cotte, François Raffi, Xavier Mabire, Armelle Pasquet, Bruno Spire, Gilles Pialoux, Marie Suzan Monti, Jean-Michel Molina, Daniela Rojas Castro, Groupe de Recherche en Psychologie Sociale (GRePS), Université Lumière - Lyon 2 (UL2), Service de Maladies Infectieuses et Tropicales [Hôpital de la Croix-Rousse - HCL], Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U1252 INSERM - Aix Marseille Univ - UMR 259 IRD), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Coalition PLUS [Pantin, France], Hôpital l'Archet, Service des maladies infectieuses et tropicales [CHU Tenon], CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service des Maladies Infectieuses et Tropicales [Hôpital Gustave Dron, Tourcoing], Centre Hospitalier Gustave Dron [Tourcoing], Centre hospitalier universitaire de Nantes (CHU Nantes), Service de maladies infectieuses et tropicales [Saint-Louis], Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), HAL AMU, Administrateur, Service de Maladies infectieuses et tropicales [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)

Subjects
Male, Gerontology, Health (social science), HIV Infections, law.invention, 0302 clinical medicine, Randomized controlled trial, law, negotiation, Transgender, 030212 general & internal medicine, Empowerment, Community-based care, Qualitative Research, Randomized Controlled Trials as Topic, media_common, Community Health Workers, education.field_of_study, Middle Aged, PrEP, 3. Good health, Negotiation, Infectious Diseases, France Read More: https://guilfordjournals.com/doi/10.1521/aeap.2019.31.3.259, Feeling, Pill, Female, 0305 other medical science, Psychology, Adult, Community-Based Participatory Research, Anti-HIV Agents, Sexual Behavior, media_common.quotation_subject, Population, Transgender Persons, Interviews as Topic, 03 medical and health sciences, ANRS-IPERGAY, Double-Blind Method, Humans, Homosexuality, Male, education, community-based care, 030505 public health, Public Health, Environmental and Occupational Health, HIV, empowerment, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Pre-Exposure Prophylaxis, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie
Abstract

International audience; ANRS-IPERGAY was a community-based randomized trial investigating the efficacy of sexual activity-based HIV pre-exposure prophylaxis (PrEP) in a population of males and transgender females who had sex with men and were at high risk of HIV infection. We qualitatively analyzed the support provided to participants by community-based health workers (CBHW) throughout the trial's double-blind and open-label extension phases. In particular, we showed that the relationship between participants and CBHW strongly influenced self-managed pill intake. The delicate construction of this relationship, balanced between trust and dependence, played an important role in PrEP adherence. CBHW had to deal with various issues surrounding participants' feelings of empowerment regarding their role in the trial, as well as related tensions between various logics and rationalities. They were essential to participants' continued involvement.

Published
2019
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29. On-demand pre-exposure prophylaxis with tenofovir disoproxil fumarate plus emtricitabine among men who have sex with men with less frequent sexual intercourse: a post-hoc analysis of the ANRS IPERGAY trial

Author

Laurence Meyer, Julie Chas, Jean-Guy Baril, Véronique Doré, Michel Morin, Jean-Pierre Aboulker, Marine Saouzanet, Isabelle Durant-Zaleski, Marie Suzan-Monti, Emmanuelle Netzer, Françoise Euphrasie, Nathalie Bajos, Séverine Gibowski, Soizic Le Mestre, Gilles Peytavin, Jean-François Delfraissy, Constance Delaugerre, David Thompson, Brigitte Guillon, Gilles Pialoux, Alpha Diallo, Nicolas Etien, Christian Chidiac, Michel Besnier, Isabelle Charreau, Benoit Trottier, Baptiste Demoulin, Julie Timsit, Bruno Spire, Joanne Otis, Laurent Cotte, Julien Fonsart, W. Rozenbaum, Mark A. Wainberg, Gabriel Girard, Eric Cua, Guillemette Antoni, Daniela Rojas Castro, Catherine Capitant, Luis Sagaon-Teyssier, Antoine Cheret, Marie-Christine Simon, Cécile Tremblay, Nicolas Leturque, Johan Binesse, Diane Carette, Valérie Foubert, Anaïs Mennecier, Grégoire Cattin, Jean-Michel Molina, Yacine Saïdi, Nicolas Lorente, Elias Choucair, François Raffi, Cecile Rabian, Armelle Pasquet, Marie Préau, Thomas Huleux, Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Essais Thérapeutiques et Maladies Infectieuses, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CR CHUM), Centre Hospitalier de l'Université de Montréal (CHUM), Université de Montréal (UdeM)-Université de Montréal (UdeM), Génomes, biologie cellulaire et thérapeutiques (GenCellDi (UMR_S_944)), Collège de France (CdF (institution))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Hôpital Archet 2 [Nice] (CHU), Coalition PLUS [Pantin, France] (Community Research Laboratory Pantin), Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U1252 INSERM - Aix Marseille Univ - UMR 259 IRD), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Observatoire régional de la santé Provence-Alpes-Côte d'Azur [Marseille] (ORS PACA), Centre d’Investigation Clinique de Nantes (CIC Nantes), Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes), CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Gustave Dron [Tourcoing], Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL), ANRS (France Recherche Nord and Sud Sida-HIV Hépatites), the Canadian HIV Trials Network, Fonds Pierre Bergé (Sidaction), Gilead Sciences, and the Bill & Melinda Gates Foundation., ANRS IPERGAY study group: Jean-Pierre Aboulker, Nathalie Bajos, Jean-Guy Baril, Michel Besnier, Johan Binesse, Diane Carette, Grégoire Cattin, Antoine Chéret, Christian Chidiac, Elias Choucair, Jean-François Delfraissy, Baptiste Demoulin, Alpha Diallo, Isabelle Durant-Zaleski, Véronique Doré, Nicolas Etien, Françoise Euphrasie, Julien Fonsart, Valérie Foubert, Séverine Gibowski, Gabriel Girard, Brigitte Guillon, Soizic Le Mestre, France Lert, Nicolas Leturque, Nicolas Lorente, Anaïs Mennecier, Michel Morin, Emmanuelle Netzer, Joanne Otis, Armelle Pasquet, Gilles Peytavin, Gilles Pialoux, Marie Préau, Cécile Rabian, Willy Rozenbaum, Luis Sagaon-Teyssier, Yacine Saïdi, Marine Saouzanet, Marie-Christine Simon, Marie Suzan-Monti, David Thompson, Julie Timsit, Benoît Trottier, Mark Wainberg, Dupuis, Christine, Génomes, biologie cellulaire et thérapeutiques (GenCellDi (U944 / UMR7212)), Collège de France (CdF (institution))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)

Subjects
0301 basic medicine, Male, MESH: Sexual Behavior, Epidemiology, [SDV]Life Sciences [q-bio], HIV Infections, Men who have sex with men, MESH: HIV-1, Pre-exposure prophylaxis, Sexual and Gender Minorities, 0302 clinical medicine, MESH: Tenofovir, Medicine, MESH: Double-Blind Method, 030212 general & internal medicine, MESH: Incidence, MESH: Anti-HIV Agents, education.field_of_study, Incidence (epidemiology), Incidence, MESH: HIV Infections, 3. Good health, [SDV] Life Sciences [q-bio], MESH: Sexual and Gender Minorities, Infectious Diseases, Pill, France, medicine.drug, Adult, medicine.medical_specialty, Canada, Anti-HIV Agents, Sexual Behavior, Immunology, Population, Placebo, Emtricitabine, Medication Adherence, MESH: Homosexuality, Male, 03 medical and health sciences, Double-Blind Method, MESH: Canada, Virology, Internal medicine, Humans, Homosexuality, Male, education, Tenofovir, MESH: Humans, business.industry, MESH: Adult, MESH: Medication Adherence, 030112 virology, MESH: Male, MESH: France, Sexual intercourse, HIV-1, Pre-Exposure Prophylaxis, business, MESH: Pre-Exposure Prophylaxis
Abstract

Summary Background ANRS IPERGAY found that on-demand pre-exposure prophylaxis (PrEP) with oral tenofovir disoproxil fumarate plus emtricitabine was associated with an 86% relative reduction of HIV-1 incidence compared with placebo among men who have sex with men at high risk of HIV. We aimed to investigate whether on-demand PrEP was similarly effective among individuals with lower exposure to HIV risk. Methods Participants in the ANRS IPERGAY trial were randomly assigned to receive PrEP (fixed-dose combination of 300 mg tenofovir disoproxil fumarate and 200 mg emtricitabine per pill) or placebo. The primary endpoint was the diagnosis of HIV-1 infection. Pill uptake was assessed by counting returned pills at each follow-up and by estimating tenofovir concentration from frozen plasma samples. Participants were interviewed at each visit to assess the pattern of PrEP use. All participants enrolled in the modified intention-to-treat population of the double-blind phase of the ANRS IPERGAY trial were eligible for this post-hoc analysis. We calculated the total follow-up time for periods of less frequent sexual intercourse with high PrEP adherence (15 pills or fewer per month taken systematically or often during sexual intercourse). To estimate the time of HIV acquisition, fourth-generation HIV-1/2 ELISA assays, plasma HIV-1 RNA assays, and western blot analyses were done with use of frozen samples, and the stage of HIV infection was defined according to Fiebig staging. HIV incidence was compared between the two treatment groups among individuals who had less frequent sexual intercourse with high PrEP adherence. The ANRS IPERGAY trial is registered with ClinicalTrials.gov , NCT01473472 . Findings 400 participants who were randomly assigned to receive PrEP (n=199) or placebo (n=201) between Feb 22, 2012, and Oct 17, 2014, were included in this analysis. 270 participants had at least one period of less frequent sexual intercourse with high PrEP adherence during the study, representing 134 person-years of follow-up and 31% of the total study follow-up. During these periods, participants in both groups reported a median of 5·0 (IQR 2·0–10·0) episodes of sexual intercourse per month and used a median of 9·5 (6·0–13·0) pills per month. Six HIV-1 infections were diagnosed in the placebo group (HIV incidence of 9·2 per 100 person-years; 95% CI 3·4–20·1) and none were diagnosed in the tenofovir disoproxil fumarate plus emtricitabine arm (HIV incidence of 0 per 100 person-years; 0–5·4; p=0·013), with a relative reduction of HIV incidence of 100% (95% CI 39–100). Interpretation A choice between daily or on-demand PrEP regimens could be offered to men who have sex with men who have less frequent sexual intercourse. Funding ANRS (France Recherche Nord and Sud Sida-HIV Hepatites), the Canadian HIV Trials Network, Fonds Pierre Berge (Sidaction), Gilead Sciences, and the Bill & Melinda Gates Foundation.

Published
2019
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30. In-depth Sampling of High-risk Populations to Characterize HIV Transmission Epidemics Among Young MSM Using PrEP in France and Quebec

Author

Marie Laure Chaix, Gilles Pialoux, Davey M. Smith, Jean-Michel Molina, Alix Armero, Eric Cua, Catherine Capitant, Cécile Tremblay, Marie Laure Néré, Bluma G. Brenner, Cécile Goujard, Nicolas Leturque, Constance Delaugerre, Antoine Chaillon, and Laurence Meyer

Subjects
0301 basic medicine, Human immunodeficiency virus (HIV), medicine.disease_cause, Men who have sex with men, law.invention, 03 medical and health sciences, Pre-exposure prophylaxis, 0302 clinical medicine, Interquartile range, law, medicine, Major Article, 030212 general & internal medicine, MSM, Hiv transmission, business.industry, HIV, PrEP, 030104 developmental biology, Infectious Diseases, Transmission (mechanics), Oncology, Cohort, network, business, Viral load, Demography, clustering
Abstract

Background A better understanding of HIV transmission dynamics among populations at high risk is important for development of prevention strategies. We determined HIV transmission networks from infected individuals enrolled in the pre-exposure prophylaxis (PrEP) IPERGAY trial in combination with the ANRS PRIMO and Montreal PHI cohorts to identify and characterize active clusters of transmission in this high-risk population. Methods Genotypic resistance tests were performed on plasma samples from 31 IPERGAY participants. Reverse transcriptase sequences were analyzed in combination with unique HIV pol sequences from 1351 individuals enrolled in the PRIMO ANRS cohort (1999–2014) and 511 individuals enrolled in the Montreal PHI cohort (1996–2016). Network analyses were performed to infer putative relationships between all participants. Results Overall, 1893 participants were included. Transmission network analyses revealed that 14 individuals (45.2%) from the IPERGAY trial were involved in 13 clusters sampled over a median period (interquartile range) of 2 (0.3–7.8) years, including 7 dyads and 6 larger clusters ranging from 4 to 28 individuals. When comparing characteristics between clustering individuals enrolled in the PRIMO cohort (n = 377) and in IPERGAY (n = 14), we found that IPERGAY participants had a higher viral load (5.93 vs 5.20 log10 copies/mL, P = .032) and reported a higher number of partners in the last 2 months (P < .01). Conclusions These results demonstrate high rates of HIV transmission clustering among young high-risk MSM enrolled in the IPERGAY trial. In-depth sampling of high-risk populations may help to uncover unobserved transmission intermediaries and improve prevention efforts that could be targeted to the most active clusters.

Published
2019

31. Pleasure and PrEP: Pleasure-Seeking Plays a Role in Prevention Choices and Could Lead to PrEP Initiation

Author

Bruno Spire, Costanza Puppo, Marie Suzan-Monti, Marie Préau, Claire Pintado, Eric Cua, Xavier Mabire, Jean-Michel Molina, Daniela Rojas Castro, Marion Mora, Stéphane Morel, Julie Chas, Groupe de Recherche en Psychologie Sociale (GRePS), Université Lumière - Lyon 2 (UL2), AIDES, Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U1252 INSERM - Aix Marseille Univ - UMR 259 IRD), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital l'Archet, Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)

Subjects
Adult, Male, Pleasure, Health (social science), media_common.quotation_subject, Sexual Behavior, sexual health, lcsh:Medicine, Context (language use), Human sexuality, HIV Infections, physiological and endocrine disorders, Men who have sex with men, law.invention, Interviews as Topic, 03 medical and health sciences, 0302 clinical medicine, Acquired immunodeficiency syndrome (AIDS), Condom, law, medicine, Humans, 030212 general & internal medicine, Homosexuality, Male, media_common, Reproductive health, Aged, health-care issues, 030505 public health, business.industry, lcsh:R, Public Health, Environmental and Occupational Health, Middle Aged, medicine.disease, 3. Good health, sexuality, Sexual intercourse, Bisexuality, HIV/AIDS, Original Article, Pre-Exposure Prophylaxis, health promotion and disease prevention, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, 0305 other medical science, business, Psychology, Social psychology
Abstract

International audience; Pleasure-seeking plays a role in prevention (means choices and use), and in the sexual quality of life of men who have sex with men (MSM). Since HIV is a major threat to MSM health, new means of prevention, like pre-exposure prophylaxis (PrEP), must meet the needs of MSM to be fully efficient. Using a psychosocial approach, we examined how pleasure-seeking plays a role in participation of MSM in “ANRS-IPERGAY,” a community-based trial on sexual health which included sexual on-demand PrEP. Thirteen semistructured collective interviews were conducted with 45 participants. First, we analyzed participants’ search for new prevention means due to previous failures in condom use. We found that participants perceived condoms as a barrier—both materially and symbolically—to pleasure and desire, causing anxiety and stress considering sexual intercourse. Second, we explored representations and attitudes concerning pleasure within the context of PrEP. We found that PrEP allowed participants to freely choose their desired sexual positions and to better enjoy intimacy. Third, we studied the sexual quality of life for PrEP users in ANRS-IPERGAY and found an improvement. Thanks to the community-based design of the trial, this new prevention tool became a means to develop agency and empowerment for participants, not only in negotiating individual prevention but also in opposing the normative and stigmatizing discourse on sexuality and HIV. In conclusion, pleasure-seeking appears to be an essential element of sexual fulfillment that needs to be integrated as a positive notion in the study of HIV prevention.

Published
2019
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32. First year of pre-exposure prophylaxis implementation in France with daily or on-demand tenofovir disoproxil fumarate/emtricitabine

Author

F Durand, Laurent Cotte, C Pintado, Jade Ghosn, M. Siguier, Eric Cua, M. Ohayon, Nadia Valin, J.-M. Molina, R Mera, Gilles Pialoux, Julie Chas, and G Barriere

Subjects
0301 basic medicine, Microbiology (medical), Adult, Male, medicine.medical_specialty, Multivariate analysis, Anti-HIV Agents, Context (language use), HIV Infections, Comorbidity, Logistic regression, Emtricitabine, Men who have sex with men, 03 medical and health sciences, Pre-exposure prophylaxis, 0302 clinical medicine, Internal medicine, Outcome Assessment, Health Care, Odds Ratio, Medicine, Humans, Pharmacology (medical), 030212 general & internal medicine, Medical prescription, Homosexuality, Male, Tenofovir, Pharmacology, Unsafe Sex, business.industry, Health Plan Implementation, Middle Aged, 030112 virology, Regimen, Infectious Diseases, Female, Pre-Exposure Prophylaxis, France, business, medicine.drug
Abstract

BackgroundIn January 2016, the French Medicine Agency initiated a Temporary Recommendation for Use (TRU) to allow the use of oral intake of tenofovir disoproxil fumarate and emtricitabine for pre-exposure prophylaxis (PrEP) in adults at high risk of HIV. We report the results of the first year of PrEP implementation in France.MethodsData were collected by physicians using a secured web subject-monitoring interface, with two forms: an initiation form, with patients’ baseline characteristics, and an HIV seroconversion form. Univariate and adjusted multivariate analysis using a logistic regression model were performed to identify baseline factors associated with on-demand PrEP regimen prescription.ResultsFrom 4 January 2016 to 28 February 2017, 3405 subjects were enrolled, with 2774 initiation forms completed; 98.1% were male and 96.9% were MSM. An on-demand regimen was prescribed to 57% of subjects. Older age (OR for participants older than 50 years = 1.76, 95% CI 1.35–2.3, P ConclusionsIn a real-life setting in France, PrEP was used, either daily or on-demand, mostly by MSM, with breakthrough infections being rare.

Published
2019

33. Safety of elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide in HIV-1-infected adults with end-stage renal disease on chronic haemodialysis: an open-label, single-arm, multicentre, phase 3b trial

Author

Jihad Slim, Moupali Das, Shuping Jiang, Aimee M. Wilkin, Andrew T. A. Cheng, Eric Cua, Robert C. Kalayjian, Joseph J. Eron, Cheryl McDonald, Anson K Wurapa, Jeffrey L. Stephens, Sophia Majeed, Stephanie Cox, Brigitte Schmied, Devi SenGupta, Jean-Daniel Lelièvre, and Mehri S McKellar

Subjects
0301 basic medicine, medicine.medical_specialty, Epidemiology, business.industry, Elvitegravir, Cobicistat, Immunology, Emtricitabine, 030112 virology, Tenofovir alafenamide, End stage renal disease, 03 medical and health sciences, Regimen, 0302 clinical medicine, Infectious Diseases, Virology, Internal medicine, medicine, Outpatient clinic, 030212 general & internal medicine, Adverse effect, business, medicine.drug
Abstract

Background: Current treatment for HIV-infected individuals with renal failure on haemodialysis frequently requires complex regimens with multiple pills. A daily single-tablet regimen of coformulated elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide is approved in Europe, the USA, and in other regions for use in HIV-1-infected individuals with mild-to-moderate chronic kidney disease (creatinine clearance 30–69 mL/min). We aimed to assess the safety, efficacy, and pharmacokinetics of this regimen in HIV-infected adults with end-stage renal disease on chronic haemodialysis. Methods: We did an open-label, single-arm, multicentre, phase 3b trial at 26 outpatient clinics in Austria, France, Germany, and the USA. Participants were HIV-1-infected adults with end-stage renal disease (creatinine clearance

Published
2019
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34. Pre-exposure prophylaxis: a useful tool to prevent human immunodeficiency virus infection?

Author

Eric Cua, J.-M. Molina, Constance Delaugerre, Laurent Cotte, Gilles Pialoux, and François Raffi

Subjects
0301 basic medicine, Microbiology (medical), medicine.medical_specialty, Anti-HIV Agents, Population, Human immunodeficiency virus (HIV), HIV Infections, medicine.disease_cause, Chemoprevention, Virus, Medication Adherence, 03 medical and health sciences, Pre-exposure prophylaxis, 0302 clinical medicine, Internal medicine, Drug Resistance, Viral, Animals, Humans, Medicine, 030212 general & internal medicine, Adverse effect, education, Clinical Trials as Topic, education.field_of_study, business.industry, Incidence (epidemiology), Vaccine trial, General Medicine, 030112 virology, Microbicides for sexually transmitted diseases, Disease Models, Animal, Treatment Outcome, Infectious Diseases, Immunology, Drug Therapy, Combination, Pre-Exposure Prophylaxis, business
Abstract

The aim of preventive measures against human immunodeficiency virus (HIV) is to reduce the incidence of HIV infection in the general population and in high-risk groups, such as men having sex with men (MSM), and to reduce the risk that a given individual will contract or spread the virus. Male and female condoms, post-exposure prophylaxis and circumcision are preventive methods currently recognized or promoted worldwide. Although modest success has been reported in a phase-III vaccine trial, other methods are being evaluated, such as vaginal and rectal microbicides, and pre-exposure prophylaxis (PrEP). Herein, we discuss results from prevention trials, especially those focusing on PrEP and particularly on recent results from 'on-demand' PrEP regimens. The efficacy of PrEP (rates of 0%-86%) is strongly correlated with adherence and plasma concentrations of antiretrovirals. Adverse events are rare. Selection of emtricitabine-resistant strains is mainly reported in individuals with an undiagnosed HIV infection using PrEP. PrEP is now strongly recommended in WHO prevention programmes for individuals at substantial risk for HIV with a view to controlling this epidemic by 2030.

Published
2016
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35. Effect of On-Demand Oral Pre-exposure Prophylaxis With Tenofovir/Emtricitabine on Herpes Simplex Virus-1/2 Incidence Among Men Who Have Sex With Men: A Substudy of the ANRS IPERGAY Trial

Author

Isabelle Charreau, Laurence Meyer, Claire Pintado, Nadia Mahjoub, Laurent Cotte, Marie-Laure Chaix, François Raffi, Catherine Capitant, Eric Cua, Jean-Michel Molina, Gilles Pialoux, Cécile Tremblay, and Constance Delaugerre

Subjects
0301 basic medicine, medicine.medical_specialty, Tenofovir, TDF/FTC, Population, Emtricitabine, Placebo, medicine.disease_cause, HSV1/2 prevalence, Men who have sex with men, 03 medical and health sciences, Pre-exposure prophylaxis, 0302 clinical medicine, Internal medicine, medicine, 030212 general & internal medicine, MSM, education, education.field_of_study, business.industry, Incidence (epidemiology), Brief Report, PrEP, 030104 developmental biology, Infectious Diseases, Herpes simplex virus, Oncology, HSV1/2 incidence, business, medicine.drug
Abstract

We evaluated the impact of on-demand oral tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC) for pre-exposure prophylaxis (PrEP) on herpes simplex virus (HSV)-1/2 incidence among men who have sex with men (MSM) enrolled in the ANRS IPERGAY trial. Serum samples were tested at baseline and at the last visit for HSV-1/2 antibodies. Overall HSV-1 incidence was 11.7 per 100 person-years; 16.2 and 7.8 per 100 person-years in the TDF/FTC and placebo arm, respectively (P = .19). Overall HSV-2 incidence was 7.6 per 100 person-years; 8.1 and 7.0 per 100 person-years in the TDF/FTC and placebo arm, respectively (P = .75). On-demand oral PrEP with TDF/FTC failed to reduce HSV-1/2 incidence in this population.

Published
2018

36. The ANRS-Ipergay trial, an opportunity to use qualitative research to understand the perception of the 'participant'-physician relationship

Author

Marion Di Ciaccio, Marie Suzan-Monti, Martin Siguier, Eric Cua, Laurent Cotte, Bruno Spire, Marie Préau, Jean-Michel Molina, Daniela Rojas Castro, Christel Protière, Julie Chas, Di Ciaccio, Marion, Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U1252 INSERM - Aix Marseille Univ - UMR 259 IRD), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Groupe de Recherche en Psychologie Sociale (GRePS), Université Lumière - Lyon 2 (UL2), Observatoire régional de la santé Provence-Alpes-Côte d'Azur [Marseille] (ORS PACA), AIDES [Pantin, France] (Mission Innovation Recherche Expérimentation), Coalition Internationale Sida [Pantin, France] (Programme Recherche Communautaire), Service de Maladies infectieuses et tropicales [CHU Tenon], CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service des maladies infectieuses et tropicales [CH Lyon Sud - HCL] (Hôpital de la Croix-Rousse), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL)-Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL), Génétique et Ecologie des Virus, Génétique des Virus et Pathogénèse des Maladies Virales, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département des Maladies Infectieuses [CHU Nice] (Hôpital de l'Archet), Hôpital l'Archet - CHU de Nice, Service des Maladies Infectieuses et Tropicales, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), ANRS IPERGAY Study Group, Epidémiologie et Sciences Sociales Appliquées à l'Innovation Médicale, Université de la Méditerranée - Aix-Marseille 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U912 INSERM - Aix Marseille Univ - IRD), Service des Maladies Infectieuses et Tropicales [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Tenon [APHP], Equipe 16, Centre de Recherche en Cancérologie de Lyon (CRCL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Centre Hospitalier Universitaire de Nice (CHU Nice), Service de maladies infectieuses et tropicales [Saint-Louis], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Service des maladies infectieuses et tropicales [CHU Tenon], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL)-Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)

Subjects
Adult, Counseling, Male, medicine.medical_specialty, Health (social science), Social Psychology, Anti-HIV Agents, ANRS-IPERGAY trial, media_common.quotation_subject, Identity (social science), [SHS.PSY]Humanities and Social Sciences/Psychology, HIV Infections, Context (language use), Men who have sex with men, Paternalism, Condoms, [SHS.PSY] Humanities and Social Sciences/Psychology, 03 medical and health sciences, 0302 clinical medicine, Physicians, Perception, Humans, Medicine, 030212 general & internal medicine, Homosexuality, Male, Medical prescription, patient-as-partner, Qualitative Research, ComputingMilieux_MISCELLANEOUS, media_common, Physician-Patient Relations, 030505 public health, Patient-physician relationship, business.industry, Public Health, Environmental and Occupational Health, Middle Aged, PrEP, 3. Good health, Sexual Partners, Family medicine, Female, Pre-Exposure Prophylaxis, 0305 other medical science, business, Construct (philosophy), Qualitative research
Abstract

International audience; The ANRS-IPERGAY trial consisted in providing sexual activity-based antiretroviral prophylaxis for HIV prevention (PrEP) with a package of prevention tools (counselling, condoms, HIV and sexually transmitted infections' screening) to highly exposed HIV-negative men who have sex with men (MSM). Few data exist concerning the patient-physician relationship in the particular context of PrEP, where physicians discuss sexual behaviours with MSM who are not classic patients, in that consultation is for prevention purposes, not for illness. This study took place during the open-label extension of ANRS-IPERGAY trial when all participants received PrEP. In this qualitative study, we examined how physicians perceived their relationship with participants in the ANRS-IPERGAY trial. Of all 30 physicians involved in the trial who were contacted by email to participate in an interview about their opinions and perceptions of ANRS-IPERGAY 18 volunteered to participate in the current sub-study. We performed a vertical analysis for each interview to identify the extract in each physician's discourse concerning their relationship with MSM participants, and conducted a horizontal analysis to construct the thematic tree and subsequently investigate differences and similitudes between themes. An analysis of all physicians' discourses showed that the participant-physician relationship during the trial could be described through 4 themes: (i) personal experience of the relationship, (ii) trust and non-judgement, (iii) positive relational climate and (iv) influence of physician's characteristics (age, gender, etc.) on relationship. We found that the particular context of PrEP led some physicians to adopt a patient-as-partner approach during consultations rather than a paternalist or hierarchical approach. Indeed, the close follow-up provided by the trial and the active role of patients in their own prevention care trajectory, are more compatible with the patient-as-partner approach. The prescription of PrEP may lead to an evolution in patient-physician relationships and may even modify the professional identity of physicians.

Published
2018
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37. PrEP en vie réelle : caractéristiques épidémiologiques des patients en prévention pré-exposition au VIH et incidence des infections sexuellement transmissibles notamment chez les personnes recrutées via une application de rencontre

Author

B. Prouvost-Keller, S. Manni, M. Le Maréchal, C. Etienne, Eric Cua, Pierre-Marie Roger, and Pascal Pugliese

Subjects
Infectious Diseases
Abstract

Introduction Nous disposons de peu de donnees hors etudes cliniques, concernant les personnes ayant debute une PrEP en France. Notre etude retrospective et multicentrique evalue les donnees epidemiologiques a l’inclusion, ainsi que l’incidence des infections sexuellement transmissibles (IST) au cours du suivi des utilisateurs de PrEP. Sur un des centres, une partie des beneficiaires de la PrEP a ete recrutee via une application de rencontre tres utilisee par les hommes ayant des relations sexuelles avec d’autres hommes (HSH). Materiels et methodes Sur une periode de 26 mois, nous avons recueilli les donnees des patients ayant initie du tenofovir disoproxil fumarate/emtricitabine en prophylaxie suivi dans trois centres de notre departement. La prevalence sur les deux ans precedant l’inclusion, puis sur la periode d’etude ainsi que l’incidence des ISTs ont ete calculees sur l’ensemble de la cohorte et chez les personnes recrutees via l’application de rencontre. Resultats Du 8 janvier 2016 au 28 fevrier 2018, 333 personnes ont debute une PrEP. Leur mediane d’âge est de 39 ans [IQR 30–45], 314 (94 %) sont des HSH, dont 57 (17 %) recrutes via l’application de rencontre. Chez ces derniers, on ne retrouve pas de difference en termes d’âge (p = 0,1746), d’antecedents d’IST (p = 0,14), d’usage du preservatif (p = 0,50), et de consommation de chemsex (p = 0,78) par rapport a ceux qui n’utilisent pas l’application. Sur une duree cumulee de 258 personnes-annees : une infection a VIH a ete diagnostiquee (0,39/100 personnes-annees) et 115 patients ont eu au moins une IST soit une incidence globale de 44,4/100 personnes-annees (PA), (55,1/100 PA chez les personnes utilisant l’application contre 42,3/100 PA pour le reste de la cohorte). En termes de prevalence des ISTs : on ne note pas de difference entre la prevalence dans les deux ans precedant l’inclusion (40,6 %, [109/268]) et celle calculee sur la periode d’etude (43 %, [115/268]), p = 0,646. On note une nette augmentation des ISTs rectales declarees par 9,1 % (10/109) des inclus lors du screening et presentes chez 54,7 % (63/115) des participants sur la periode de suivi. Conclusion La majorite des participants sont des HSH et ont plus de 30 ans. Le profil et l’âge des personnes recrutees par l’application de rencontre est similaire, on note cependant une incidence des ISTs plus importante dans cette sous population. Notre etude confirme la forte incidence des ISTs notamment rectales chez les utilisateurs de PrEP. Ce qui rend compte probablement de la diminution de l’usage du preservatif, et aussi du depistage systematique tous les trois mois d’infections pour la plupart asymptomatiques.

Published
2019
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38. Virologically suppressed patients with asymptomatic and symptomatic HIV-associated neurocognitive disorders do not display the same pattern of immune activation

Author

Christine Lebrun-Frenay, Brigitte Dunais, Jacques Durant, Eric Cua, L Fredouille-Heripret, Michel Ticchioni, Isabelle Cohen-Codar, N Montagne, Matteo Vassallo, S Andersen, F DeSalvador, Jacqueline Cottalorda, Roxane Fabre, C. Pradier, M. Laffon, Alexandra Harvey-Langton, and Pierre Dellamonica

Subjects
medicine.medical_specialty, business.industry, Health Policy, CD4-CD8 Ratio, Odds ratio, Disease, medicine.disease, Asymptomatic, Infectious Diseases, Internal medicine, Post-hoc analysis, Immunology, medicine, Dementia, Pharmacology (medical), medicine.symptom, business, Viral load, Neurocognitive
Abstract

Objectives Inversion of the CD4:CD8 ratio is a marker of immune activation and age-associated disease. We measured the CD4:CD8 ratio as a marker of cognitive impairment in HIV-infected patients and explored differences according to clinical severity. Methods Post hoc analysis of data from two prospective cohorts of HIV-infected patients randomly selected to undergo neuropsychological tests was performed. Test scores were adjusted for age, gender and education. Inclusion criteria were undetectable viral load and stable treatment for at least 6 months. Subjects with HIV-associated dementia were excluded. Patients were divided into an unimpaired group, a group with asymptomatic neurocognitive disorder (ANI) and a group with symptomatic HIV-associated neurocognitive disorder (sHAND), represented by mild neurocognitive disorder (MND). Demographic and background parameters, immune activation markers and the CD4:CD8 ratio were recorded. Results Two hundred patients were included in the study. The mean age was 52 years, 78% were male, the mean CD4 count was 624 cells/μL, the mean nadir CD4 count was 240 cells/μL, 27% were hepatitis C virus (HCV)-coinfected, the mean duration of HIV infection was 16 years, and the mean time on current combination antiretroviral therapy (cART) was 2.9 years. Twenty-nine per cent of subjects had HAND (21% had ANI and 8% had MND). In multivariate analysis, a CD4:CD8 ratio

Published
2015
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39. Assessment of HIV Screening Tests for Pre-Exposure Prophylaxis Programs

Author

Constance Delaugerre, Nolwenn Hall, Catherine Capitant, Jean-Michel Molina, Gilles Pialoux, Cécile Tremblay, Eric Cua, Nadia Mahjoub, Marie-Laure Chaix, Armelle Pasquet, Laurence Meyer, Laurent Cotte, and Guillemette Antoni

Subjects
0301 basic medicine, medicine.medical_specialty, biology, medicine.diagnostic_test, business.industry, 030106 microbiology, Drug resistance, Serology, 03 medical and health sciences, Pre-exposure prophylaxis, 0302 clinical medicine, Infectious Diseases, HIV Antigens, Antigen, Internal medicine, Immunoassay, biology.protein, Immunology and Allergy, Medicine, 030212 general & internal medicine, Antibody, business, Mass screening
Abstract

Preexposure prophylaxis programs involve frequent human immunodeficiency virus (HIV) testing. We evaluated the sensitivity of 2 antigen/antibody immunoassays (Architect and Bioplex), 2 antibody-based rapid tests (Vikia-HIV-1/2 and Autotest-VIH), and 1 antigen/antibody rapid test (Alere HIV Combo) for the diagnosis of HIV infection. Among the 31 HIV-1-infected participants in the ANRS-IPERGAY trial, HIV-1 RNA was detected alone in only 2. The sensitivities of the Architect and Bioplex assays were 83% (95% confidence interval [CI], 76%-99%) and 82% (95% CI, 63%-94%), respectively. The sensitivities of the Vikia, Autotest, and Alere tests were 54% (95% CI, 34%-72%), 50% (95% CI, 31%-69%), and 78% (95% CI, 58%-91%), respectively. Antigen/antibody tests should be preferred to avoid missing cases of acute HIV infection and to decrease the related risks of viral transmission and emergence of drug resistance.

Published
2017
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40. Efficacy and safety of clindamycin-based treatment for bone and joint infections: a cohort study

Author

Johan Courjon, E. Bernard, Eric Cua, Elisa Demonchy, and Pierre-Marie Roger

Subjects
0301 basic medicine, Microbiology (medical), Male, medicine.medical_specialty, Combination therapy, medicine.drug_class, 030106 microbiology, Antibiotics, Comorbidity, medicine.disease_cause, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Medical microbiology, Internal medicine, medicine, Humans, 030212 general & internal medicine, Osteitis, Aged, Aged, 80 and over, Arthritis, Infectious, business.industry, Medical record, Clindamycin, Disease Management, General Medicine, Middle Aged, medicine.disease, Surgery, Anti-Bacterial Agents, Infectious Diseases, Treatment Outcome, Staphylococcus aureus, Female, business, Algorithms, medicine.drug, Cohort study
Abstract

Clindamycin has high bioavailability together with good diffusion in bone tissue and could represent an alternative antibiotic compound for the treatment of bone and joint infections (BJIs). However, data regarding the efficacy and safety of clindamycin for BJIs are limited. A monocentric cohort study based on our medical dashboard, which prospectively recorded 28 characteristics for all hospitalized patients since July 2005, was performed. BJIs were selected, and then, all mono-microbial BJI managed with clindamycin-based therapy were included. Remission was defined as the absence of clinical and/or microbiological relapse after treatment. The duration of follow-up without relapse was determined retrospectively using computerized medical records. For 10 years, 196 BJIs, of which 80 (41%) were device-associated infections, were treated with clindamycin-based therapy. The bacterial causative agent was Staphylococcus aureus in 130 cases (66%), coagulase-negative staphylococci in 29 cases (15%), streptococci in 31 cases (16%) and other bacteria in 6 cases (3%). When used in combination therapy, clindamycin was mainly paired with fluoroquinolones (31%) or rifampin (27%). The mean duration of clindamycin treatment was 7.4 ± 3.2 weeks (range, 1–24). An AE was recorded for 9 (4.5%) patients. Remission was recorded for 111 (57%) patients, with a mean duration of clinical follow-up of 28 ± 24 months. Treatment failure occurred in 22 (11%) patients, 50 patients (25%) were lost to follow-up, and 8 (4%) required long-term suppressive therapy. Among the assessable patients, clindamycin-based therapy was efficient in 111/133 cases (83%) and thus represents a reliable and safe alternative treatment option.

Published
2017

41. Factors associated with partner notification of STIs in men who have sex with men on PrEP in France: a cross-sectional substudy of the ANRS-IPERGAY trial

Author

Lisa Fressard, Laurence Meyer, Jean-Michel Molina, Laurent Cotte, Marie Suzan-Monti, Catherine Capitant, Eric Cua, Gilles Pialoux, Bruno Spire, Observatoire régional de la santé Provence-Alpes-Côte d'Azur [Marseille] (ORS PACA), Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U1252 INSERM - Aix Marseille Univ - UMR 259 IRD), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Maladies Infectieuses et Tropicales [Hôpital de la Croix-Rousse - HCL], Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de Maladies Infectieuses [CHU Nice], Hôpital l'Archet - CHU de Nice, Essais Thérapeutiques et Maladies Infectieuses, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Sud - Paris 11 (UP11), Essais Therapeutiques et Infection Par Le Vih, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de maladies infectieuses et tropicales [Saint-Louis], Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), The ANRS IPERGAY trial was sponsored by the ANRS (France Recherche Nord & Sud Sida-HIV Hepatites), and funded by ANRS, the Canadian HIV Trials Network, the Fonds de dotation Pierre Bergé pour la Prévention - SIDACTION, and the Bill & Melinda Gates Foundation., ANRS IPERGAY Study Group, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], and Lissalde, Claire

Subjects
Adult, Male, medicine.medical_specialty, Casual, Sexual Behavior, Street drugs, Sexually Transmitted Diseases, Behavioural sciences, partner notification, Dermatology, 030501 epidemiology, infectious diseases, behavioural science, Men who have sex with men, Condoms, Drug Users, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Surveys and Questionnaires, Medicine, Humans, 030212 general & internal medicine, Longitudinal Studies, Homosexuality, Male, gay men, Unsafe Sex, business.industry, Public health, Extension study, Partner notification, 3. Good health, Cross-Sectional Studies, Sexual Partners, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Family medicine, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Contact Tracing, 0305 other medical science, business, Anal sex, Follow-Up Studies
Abstract

ObjectivesPartner notification (PN) is a useful public health approach to enhance targeted testing of people at high risk of HIV and other STIs, and subsequent linkage to care for those diagnosed. In France, no specific PN guidelines exist and information about current practices is scarce. We used the ANRS-IPERGAY PrEP trial to investigate PN in HIV-negative men who have sex with men (MSM) reporting a bacterial STI.MethodsThis substudy included 275 participants who completed a specific online PN questionnaire during the open-label extension study of the ANRS-Intervention Préventive de l’Exposition aux Risques avec et pour les Gays (IPERGAY) trial. Variables used as proxies of at-risk practices were defined using data collected at the previous follow-up visit about participants’ most recent sexual encounter and preventive behaviours. χ2 or Fisher’s exact test helped select variables eligible for multiple logistic models.ResultsOf the 275 participants, 250 reported at least one previous STI. Among the latter, 172 (68.8%) had informed their partner(s) of their most recent STI. Of these, 138 (80.2%) and 83 (48.3%) had notified their casual and main partners, respectively. Participants were less likely to notify their main partner when their most recent sexual encounter involved unsafe anal sex with a casual partner (adjusted OR (aOR) (95% CI) 0.18 (0.06 to 0.54), P=0.02). Older participants were less likely to inform casual partners (aOR (95% CI) 0.44 (0.21 to 0.94), P=0.03), while those practising chemsex during their most recent sexual encounter were more likely to inform their casual partners (aOR (95% CI) 2.56 (1.07 to 6.09), P=0.03).ConclusionUnsafe sexual encounters with people other than main partners and street drugs use were two sociobehavioural factors identified, respectively, as a barrier to main PN and a motivator for casual PN, in a sample of high-risk MSM. These results provide an insight into current PN practices regarding STI in France and might inform future decisions about how to define feasible and acceptable PN programmes.

Published
2017
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42. Assessment of HIV Screening Tests for Use in Preexposure Prophylaxis Programs

Author

Constance, Delaugerre, Guillemette, Antoni, Nadia, Mahjoub, Gilles, Pialoux, Eric, Cua, Armelle, Pasquet, Nolwenn, Hall, Cécile, Tremblay, Laurent, Cotte, Catherine, Capitant, Marie-Laure, Chaix, Laurence, Meyer, and Jean-Michel, Molina

Subjects
Immunoassay, HIV Antigens, HIV-1, Humans, Mass Screening, RNA, Viral, HIV Infections, Pre-Exposure Prophylaxis, Serologic Tests, HIV Antibodies, Sensitivity and Specificity, Retrospective Studies
Abstract

Preexposure prophylaxis programs involve frequent human immunodeficiency virus (HIV) testing. We evaluated the sensitivity of 2 antigen/antibody immunoassays (Architect and Bioplex), 2 antibody-based rapid tests (Vikia-HIV-1/2 and Autotest-VIH), and 1 antigen/antibody rapid test (Alere HIV Combo) for the diagnosis of HIV infection. Among the 31 HIV-1-infected participants in the ANRS-IPERGAY trial, HIV-1 RNA was detected alone in only 2. The sensitivities of the Architect and Bioplex assays were 83% (95% confidence interval [CI], 76%-99%) and 82% (95% CI, 63%-94%), respectively. The sensitivities of the Vikia, Autotest, and Alere tests were 54% (95% CI, 34%-72%), 50% (95% CI, 31%-69%), and 78% (95% CI, 58%-91%), respectively. Antigen/antibody tests should be preferred to avoid missing cases of acute HIV infection and to decrease the related risks of viral transmission and emergence of drug resistance.

Published
2017

43. Profil épidémiologique et bactériologique des gonococcies isolées en milieu hospitalier

Author

Nicolas Degand, J. Delages, Pierre-Marie Roger, L. Roudière, P. Del Giudice, Véronique Blanc, G. Keirle, and Eric Cua

Subjects
Infectious Diseases
Abstract

Introduction La recrudescence des infections sexuellement transmissibles (IST) est patente en France depuis les annees 2000. Une surveillance des phenotypes de resistance aux antibiotiques est necessaire, notamment pour Neisseria gonorrhoeae. Notre objectif etait de comparer les profils de sensibilite aux antibiotiques des gonocoques isoles dans notre region au registre national du centre national de reference des gonocoques (CNRG). Par ailleurs, nous avons analyse la realisation du bilan de depistage minimal des autres IST chez ces patients. Materiels et methodes Il s’agit d’une etude retrospective multicentrique basee sur les donnees bacteriologiques de trois laboratoires hospitaliers (un CHU et deux centres hospitaliers peripheriques) de 2014 a 2017, ainsi qu’une analyse des dossiers cliniques. Les concentrations minimales inhibitrices (CMI) aux antibiotiques ont ete determinees par bandelettes E-test sur culture en milieu gelose. L’analyse des prescriptions a la recherche de co-infections (VIH, syphilis, Chlamydia trachomatis, VHB) a ete realisee a partir des dossiers medicaux. Resultats Un total de 103 infections a gonocoque a ete analyse. Celles-ci ont ete observees essentiellement chez de jeunes hommes adultes : sex-ratio H/F de 7 et 71,2 % (52/73) de moins de 35 ans. La sensibilite vis-a-vis des penicillines G est de 19,4 % (20/103) versus 20,9 % (88/421) pour le CNRG. Pour les fluoroquinolones, la sensibilite est de 53,4 % (55/103) versus 43 % (511/1188). Pour la ceftriaxone, aucune souche resistante n’est isolee, de meme qu’au CNRG. Le depistage des autres IST inclut le VIH dans 52 % (38/73) des cas, la syphilis dans 48 % (35/73), le VHB dans 49,3 % (36/73) et chlamydia dans 46,6 % (34/73). On note des disparites entre les centres, pour le depistage de ces IST associees. Sur le CHU, sont principalement recherches le VIH dans 44 % (18/41) des cas et chlamydia dans 46,4 % (19/41). A l’inverse, dans l’un des centres hospitaliers peripheriques, on retrouve une predominance de la recherche de la syphilis et du VHB dans 82 % (9/11) et 72,8 % (8/11) des cas, respectivement. Dans un autre centre hospitalier peripherique, les resultats sont homogenes avec la recherche du VIH a 62,6 % (13/21), de la syphilis a 57,6 % (12/21), de chlamydia a 52,8 % (11/21) et du VHB a 62,6 % (13/21). Une autre IST est ainsi depistee dans 27,4 % (20/73) des cas. Conclusion L’adequation de la sensibilite du gonocoque aux principaux antibiotiques utilises dans le traitement de reference au niveau regional est superposable aux statistiques nationales. Par contre, la recherche des autres IST associees, au moment du diagnostic, n’est realisee que dans un cas sur deux, et ce de facon homogene entre les centres. Le bilan minimal de depistage est donc insuffisamment realise en milieu hospitalier.

Published
2018
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44. 2490. Longer-Term Safety and Efficacy of Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide in Virologically Suppressed Adults Living With HIV and End-Stage Renal Disease on Chronic Hemodialysis

Author

Eric Cua, Christiana Blair, Cheryl McDonald, Robert Kalayjian, Arjun Wilkin, Moupali Das, Joseph J. Eron, Jihad Slim, Jeffrey L. Stephens, Sophia Majeed, Christoph C Carter, Anson K Wurapa, Mehri S McKellar, Diana M. Brainard, Jean-Daniel Lelièvre, Devi SenGupta, and Stephanie Cox

Subjects
medicine.medical_specialty, Intention-to-treat analysis, Elvitegravir/cobicistat/emtricitabine/tenofovir, business.industry, medicine.medical_treatment, Human immunodeficiency virus (HIV), medicine.disease_cause, medicine.disease, Tenofovir alafenamide, End stage renal disease, Abstracts, Infectious Diseases, Peripheral neuropathy, Oncology, Quality of life, Internal medicine, Poster Abstracts, medicine, Hemodialysis, business
Abstract

Background HIV treatment for individuals with end-stage renal disease (ESRD) on hemodialysis (HD) has previously required complex dose-adjusted regimens. We evaluated the safety and efficacy of single-tablet, once-daily elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) in people living with HIV (PLH) and ESRD on chronic HD. Methods Virologically suppressed adult PLH with ESRD on chronic HD for ≥ 6 months were switched to open-label E/C/F/TAF 150/150/200/10 mg once daily for 96 weeks. Efficacy was assessed as the proportion of participants who maintained virologic suppression (HIV RNA < 50 copies/mL) using the snapshot algorithm. Safety and participant satisfaction were assessed throughout the study. Results We enrolled 55 participants with median age 51 years (range 23–64) with median time on HD 6 years (range 1–17). In the per protocol analysis set, virologic suppression was maintained in 30 of 31 participants (96.8%, 95% CI [83.3%, 99.9%]) at week 96. In the full analysis set, virologic suppression was maintained in 30 of 55 participants (54.5%; 95% CI [40.6%, 68.0%]); one discontinued therapy due to lack of efficacy, and W96 data were unavailable for 24. Of the 24 participants lacking W96 data, 17 discontinued study drug early and 7 had missing data while on study drug; all had HIV RNA < 50 copies/mL at the last pre-week 96 check. Treatment-emergent AEs occurred in 53 (96.4%) participants, and study-drug-related AEs occurred in 7 (12.7%). Treatment-emergent AEs leading to premature study drug discontinuation occurred in 4 (7.3%) participants; two were considered study-drug-related (allergic pruritus and peripheral neuropathy in one participant each). No study-drug-related serious AEs were observed. 85.7% (30/35) of responding participants reported they were ‘much more satisfied’ with their regimen. Conclusion Single-tablet, once-daily E/C/F/TAF was effective in maintaining virologic suppression in PLH on chronic HD over 96 weeks of follow-up. E/C/F/TAF was well tolerated and was associated with improved participant satisfaction. These data demonstrate that E/C/F/TAF is a safe and effective alternative to more complicated regimens in PLH on chronic HD, with the potential to improve patient satisfaction and quality of life. Disclosures All authors: No reported disclosures.

Published
2019
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45. Antibiotics-related adverse events in the infectious diseases department of a French teaching hospital: a prospective study

Author

E. Bernard, K. Risso, Céline Pulcini, Eric Cua, Pierre-Marie Roger, Johan Courjon, and F. Guillouet

Subjects
Adult, Male, Microbiology (medical), medicine.medical_specialty, Pediatrics, Drug-Related Side Effects and Adverse Reactions, medicine.drug_class, Antibiotics, Hospital Departments, Fosfomycin, Communicable Diseases, chemistry.chemical_compound, Medical microbiology, medicine, Humans, Prospective Studies, Medical prescription, Hospitals, Teaching, Prospective cohort study, Adverse effect, Aged, Aged, 80 and over, Infectious Disease Medicine, business.industry, Incidence, Incidence (epidemiology), General Medicine, Middle Aged, Anti-Bacterial Agents, Infectious Diseases, chemistry, Linezolid, Female, France, business, medicine.drug
Abstract

Antibiotics are a significant cause of adverse events (AE), but few studies have focused on prescriptions in hospitalized patients. In infectious diseases departments, the high frequency and diversity of antibiotics prescribed makes AE post-marketing monitoring easier. The aim of our study was to assess the incidence and type of AE in the infectious diseases department of a French teaching tertiary-care hospital. The main characteristics of each hospitalization, including all antibiotics prescribed and any significant AE were recorded prospectively in the medical dashboard of the department. We included all patients having suffered an AE due to systemic antibiotics between January 2008 and March 2011. Among the 3963 hospitalized patients, 2682 (68 %) received an antibiotic and 151/2682 (5.6 %) suffered an AE. Fifty-two (34 %) AE were gastrointestinal disorders, 32 (21 %) dermatological, 20 (13 %) hepatobiliary, 16 (11 %) renal and urinary disorders, 13 (9 %) neurological and 11 (7 %) blood disorders. Rifampin, fosfomycin, cotrimoxazole and linezolid were the leading causes of AE. Sixty-two percent of the antibiotics causing an AE were stopped and 38 % were continued (including 11 % with a dose modification). Patients suffering from AE had an increased length of stay (18 vs 10 days, P < 0.001). Our data could help choosing the safest antibiotic when several options are possible.

Published
2013
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46. Clinical features and prognostic factors of listeriosis: the MONALISA national prospective cohort study

Author

Odile Fremin-Batteux, Juliette Clarissou-Philippe, Benoît Jauhlac, Severine Guyetand, Jacques Gasnault, Corinne Haioun, Liamine Aissaoui, Marie-Christine Pages, Marie-Pierre Fos, Christian Rose, Didier Hubert, Marie-Rose Rothe, N. Bouziges, Benoît Huc, François Devianne, Sabine Bidart, Anne Forest, Kevin Bertrand, Mohamed Eldeghedy, Annick Verhaeghe, Caroline Malderet, Anne Bertrou, Bernard Guerquin, Catherine Duche, Muriel Archambaud, Rabea Cotteret, Olivier Toullalan, Yves Devaux, Smail Bergheul, Valérie Sivadon-Tardy, Pierre-Gilles Merville, Geneviève Blanchard-Marche, Didier Raoult, Bernard Hory, Florence Richardin, Evelyne Belle, Mohamed Menouar, K Guitteaud, Mohamad Mohty, Ambroise Montcriol, Max Laurin, Aurélia Picard, Jean-Paul Mira, Marie-Charlotte Chopin, Richard Bonnet, Michel Wolff, Sébastien Maillez, Jeanne Maugein, Véronique Leblond, Nicola Walid, Bernard Gauche, Mathieu Evillard, Hassen Jeddi, Anne Bourlet, Isabelle Grawey, Thierry Jault, Sandrine Hiret, Valerie Gaborieau, Véronique Boin-Gay, An Kim, Thierry Constans, Jean-François Gaide, Martine Giraud, Eric Meaudre Desgouttes, Alain Fur, Abdallah Maakaroun, Olivier Matray, Bertrand Maubert, Frédérique Péchinot, Aurelie Garbi, Claire Delbrouck, Benoît Grandclerc, Vincent Cadiergue, Hervé Lécuyer, Bernadette Grignon, Thierry Bensaid, Nicole Constantin, Yannick Chevalier, Hassène Rahmani, Thierry Levent, Joelle Desliers, Florence Van de Velde, Xavier Adhoute, Clara Andriau, Christophe Charasse, Rémi Vatan, Benoît Martha, Alain Lecis, Didier Albert, Romain Jacobs, Hélène Lefranc, Christian Martin, Nasseur Rezgui, Bertrand Pigeon, Catherine Le Henaff, Dominique Cassignard, Françoise Cotes, Eric Pujade Lauraine, Jean-François Gattault, Nicole Ferreira-Maident, Noémie Jourde-Chiche, Hélène Garrec, Olivier Darchen, Carole Schwebel, Marie-Christine Bezian, Patrick Daoud, Tsouria Becaid, Simone Laluque, David Broche, Christine Boisselier, Pascale Martres, Sarah Hammami, Brigitte Olivier, Jean-Marie Nkunzimana, Eric Monlun, Isabelle Marterl-Lafay, Marion Carboni, Marie-Françoise Mattei, Sandrine Castelin, Isabelle Barillot, Marie-Noelle Cufi, Thomas Kaiser, Catherine Herry, Pascal Hutin, Jean-Pierre Bronowicki, Bernard Branger, Pierre Thomas, Elie Zagdoun, Anne Goquelin, Ziad Assaf, Ingrid Croquet, Bruno Pozzetto, Thomas Similowski, Anne-Isabelle Briere, Marie-Thérèse Albertini, Mariam Blaka, Christelle Tassot, Anne Gaschet, Jean-Philippe Lavigne, Antoine Pujol, Philippe Colombat, Edouard Devaud, Hana Talabani-Boizot, François Barière, Anne-Marie Cordier, Philippe Gueudet, Georges Simon, Anne-Sophie Lipovac, Françoise Bandaly, Anne Beauplet-Lepage, Sylvie Prince, Charlotte Jouzel, Jean-Luc Deboutin, Patrick Zavadil, Louis Puybasset, Marie-Cécile Petit, Loïc Guillevin, Kamel Touati, Christophe Ntalu Nkato, Sylvie Carette, Jacques Vaucel, Chantal Delasalle, Marine Gross Goupil, Laurent Gutmann, Christiane Payen, Annick Barboteau, Firouzé Bani-Sadr, Christophe Legendre, Philippe Roulier, Elie Azria, Ibrahim Farah, Isabelle Rouquette-Vincent, Anne-Sophie Erena-Penet, Philippe Labadie, Eric Josien, Aicha Derragui, Mathieu Legrand, Odile Beyne-Rauzy, Jean-Marc Nabholtz, Marie-Joelle Demarcq, Olivier Garosi, Michel Deiber, Fabrice Chaix, Bertrand Souweine, Anne Collignon, Gisèle Renard, Mickael Jego, Gilles Bernardin, Anne Allart, Jocelyn Barrier, Marc Vasse, Philippe Ménager, Marc Wurmser, Abderkader Ouazir, Olivier Gontieron, Yvon Berland, Sébastien Trouiller, David Leysenne, Christophe Ozanon, Fanny Autret, Tahar Saghi, Loïc Dopeux, Sophie Benoit-Coustou, T. Fraisse, Christine Maillard, Karine Nikodijevic, Georges Kaltenbach, Angéline Jamet, Philippe Aucher, Julie Bottero, Marie-Claude Piffaut, Marianne Besnard, Florence Courillon, Marie Bonfils, Christine Ghevaert, Marie Destors, Eliette Jeanmaire, Franck Zerbib, Manuel-Luis Gameiro, T Prazuck, Laurent Mandin, Olivier Guisset, Marguerite Fines, Toufik Feddal, Agnès Jouffret, Louis Mesnard, Thomas Bourrée, Hasinrina Razafimahefa, Sylvestre Tigaud, Vincent Estève, Philippe Malherbe, Jean-Michel Salord, Pascal Adam, Bertrand Rozec, Michel Fuillet, Olivier Lemenand, Denis Quinsat, Ana Danalaché, Véronique Vialette, François Brosset, Patrick Messner Pellenc, Nicolas Heisel, Edouard Girard, Régine Martin, Olivier Garesslin, Catherine Mille, Alexandre Gascon, Marc Nicolino, Laurence Mouly, Claire Fabre, Bénédicte Ponceau, Marie-Etiennette Emeriau, Pascal Cathebras, Bérangère Bernardaud, Michèle Pérouse de Montclos, O. Arsene, Karine Grenet, Yazdan Yazdanpanah, Sten De Witte, Anne Scemla, Laurence Bouillet, Christophe Burucoa, Vincent Loffeier, Séverine Visentin, Luc Desfrere, Miloud Arabi, Frédérique Costa, Sylvie Lechat, Ali Chekroun, Raymond Ruimy, Marie, Jérôme Bizet, Xavier Nassif, Baihas Dib, Patrick Bert-Marcaz, Laurent Martin Lefèvre, Nicholas Sedillot, Blandine Cattier, Emilie Boidin, Daniel Sondag, Aude Bourrouillou, Alain Noirot, Franck Desemerie, Fréderic Heluwaert, Catherine Tamalet, Marc G. Berger, Jean-Daniel Lelièvre, Dominique Perotin, Abdelkader Bemrah, Alain Lozniewski, Bernard Borstein, Hanna Eid, Diana Suatean, Virginie Mignaut, Jean-Claude N'guyen, Valérie Le Goff, Laurent Teillet, Christophe Rolland, Gwenaël Alfonsi, Florence Lachenal, Philippe Bossi, Yves Botreau, Florence Doucet Populaire, Henry Jardel, Nicolas Gallo, Elias Jabre-Sikias, Michel Dupon, Hélène Brihier, Isabelle Patry, Alexandre Leclercq, Bernadette Tourrand, Christophe Roussel, Jean-Emmanuel Kurtz, Bénédicte Paindaveine, Simon Elhadad, Richard Sanchez, Eric Sgro, Pierre Berger, Valérie Murbach, Anne Holstein, Florence Martin, Taoufik Merabet, Amélie Benbara, Milagros Ferreyra, Laure Esposito, Pierre Delobel, Antoine Andremont, Marc Bourlière, Carole-Anne Boudy, Jean-Baptiste Gaulthier, Laurent Tacchini, Olivier Marpeau, Sonia Tesseydre, Marie-Pierre Coulhon, Nathalie Hodee, Marie-Chrsitine Conroy, Pierre Weinbreck, Roland Leclercq, Laurent Souply, Christian Bidault, Annie Elbez, Marie-Annick Lebreton, Patrick Brisou, Agnès Ferroni, Jean-Louis Pourriat, Nadia Anguel, Christian Noel, Philippe Jouvencel, Eric Pichard, Xavier Martin, Mathieu Coste, Pierre Zuber, Catherine Neuwirth, Jean-Pierre Hacot, Paul Aye, Jérôme Guinard, Yves Pean, Jean-Christophe Dengo, Fabrice Petassou, Didier Viole, Thierry Messiaen, Jean Beytout, Philippe Petitjean, Ferdinand Savare, Patrice Cuvillier, Sophie Coignard, Hélène Anglaret, Nassim Kamar, Elisabeth Chachaty, Karine Guimard, Louis Braem, Hacene Fezoui, Pierre Martin, Jean-Paul Viard, Claire Larroche, Nicolai Claudiu-Plesa, Thierry Benoit-Cattin, Olivier Moquet, Thierry Pasdeloup, David Rosay, Rodolphe Jean, Jean-Bernard Mariette, Marc Debouverie, Hervé Peltier, Mustapha Terki, Jacques Daleas, Valérie Dattin-Dorrière, Michel Vergnaud, Emmanuel Grimprel, Sylvène Rosselli, Jean-Marc Didier, Pierre Faurie, Luc Frimat, Aziza Mandjee, Sabine Etchemendy, Pierre Tissières, Jean Nakhleh, Sylvie Mariette, Christian Perronne, Bruno Carbonne, Nathalie Houssiaux-Maisonneuve, Tristan Ferry, S Beague, Anthony Sebban, Marie-Thérèse Hili, Jean-Michel De Kermadec, Lucien Brasme, Gilles Blaison, Caroline Garandeau, Jean-Pierre Sollet, Laurent Tronchon, Thierry Samson, Julien Gesquière, Nicolas Ettahar, Alain Créange, Etienne Laurens, Véronique Equy, Fréderic Bart, Bernard Bouffandeau, Christine Vaillant, Valerie Pesque, Jean-Marc Lalot, Marc Levy, Michel Kaidomar, Mihaela Saplacan, Sterenn Yvenou, Marie-Isabelle Steibach, Emmanuelle Cambau, Agnès Riche, François Fourrier, François Raffi, Mélissa Lalu, Henri Bérard, Danielle Clave, Jean-Claude Mouries, Martine Porcheron, Jean Cabalion, Richard Lamarca, Nathalie Canu, Jean-Baptiste Roseau, Annabelle Stoclin, Luca Luminitan Elena Lupean, Rémi Gebeile, Celia Salanoubat, Carole Marmouset, Pierre Bigot, Anne-Laure Breton, Pierre Kalfon, Colette Vincent, Sophie Marty, Olivier Tandonnet, Alexis Redor, Xavier Valette, Ourida Aoudia, Jacques-Arnaud Seyrig, Bertrand Beaune, Hugues Aumaitre, Georges Pinon, Yann Leveneur, Sylvie Charachon, Raoul Herbrecht, Henriette de Valk, Gary David, Julien Pouyanne, Marc Dommergues, Majed Al Chaar, Véronique Blanc-Amrane, Pascale Guillarmé Grossmann, Bruno Abraham, Yves Morel, Philippe Suel, Denis Sautereau, Olivier Guilloy, Tu Anh Tran, Frédéric Laurent, Zahir Amoura, Jacques-Olivier Bay, Zoubida Elharie-Heraux, Joyce Sibony-Prat, Bernard Guillois, Dominique Rohmer-Heitz, Audrey Barrelet, Jérémie Courouble, Jean-Paul Herry, Daniel Vittecoq, Annie Vermesch-Langlin, Jean Auroux, Claude Aubert, Thierry Harvey, Ghislaine Lamoine-Gimet, J. Riahi, Florence Soraudeau, Bachar Al-Jalaby, Caroline Périsson, Khélifa Ayouz, Florence Cardot, François Maillet, Alain Goux, Théophile Magna, Bertille de Barbeyrac, Adrien May, Dominique Andreotti, Olivier Jonquet, Hélène Dumouchel, Didier Thibaud, Philippe Morlat, Pascal Chevalet, Pascal Ancelin, Guy Chambreuil, Cécile Le Boterff, Anne Ceriez, Olivier Detante, B Pangon, Claude C.A. Bernard, Vincent Cailleaux Pierre-Etienne Cailleux, Jordi Miatello, Pierre-Yves le Berruyer, Sylvain Kouaho, Michel Briaud, Hélène Delaby, Patrick Herbecq, Christine Segonds, Véronique Jault, Pascale Brunel, Christine Dussopt, Jean Thore, Jean-Marc Thouret, Jean-Marc Kerleau, François Le Baron, Slavius Matica, Sophie Leautez-Nainville, Matthieu Pecquet, Laurent Bret, Yacine Sedjelmaci, Pierre Metton, Habiboulaye Diallo, Jany Rey Zermati, Arnaud Delahaye, Hélène Chaussade, Laurent Mandelbrot, Emilie Bessede, Olivier Casanovas, Paul Pierrot, Annick Legras, Dominique Lauque, Hélène Gatti, Jean Catineau, Ebutu Likose, Gilles Capellier, Eric Kibbrecht, Freddy Thibaut, Patrick Valadier, Chantal Lemble, Joël Gaudelus, Joelle Mellier, Joëlle Brochen, Emmanuel Gascou, Stéphane Bonacorsi, Stéphanie Bannier, Bruno Fantin, Didier Raffenot, Valérie Revel, Hakim Amroun, Huguette Negrery, Anne-Laure Fauchais, Paul Mercury, Michel Chuzeville, Christian Zumbo, Nicolas Després, Pascal Roblot, Jérôme Pasche, Jean Claude Boufetteau, Jocelyne Caillon, Julien Boileau, V. Rabier, Benjamin Manéglier, Emilie Jourdes, Franck Ceppa, Christine Recule, Nicolas Degand, Benoît Henry, Thierry Baranger, Dominique Pateron, Agnès Pélaquier, Gérard Bouchet, Hélène Fiette, Ozel Guiden, Dana Ranta, Etienne Ruppé, Nabil Chiouk, Jacques Breuil, Dominique Leduc, Véronique Loustaud, Hervé Métenier, Michel Durand, Isabelle Mahé, Leila Karaoui, Marie-José Collus, Mehran Monchi, Olivier Belmonte, Romain Blondet, Jacques Thierry, Karine Humbert, Gilles Salama, Marie-Noelle Heurtaux, Cécile Goujard, Bruno Sivery, Martial Boisseau, Redouane Dahoumane, Pierre Delour, Christian Niels Meyer, Anne Faudon-Gibelin, Gérard Poulain, Roger-Charles Luciani, J.-C. Souquet, Olivier Grossi, François Vandenesch, Sylvain Mermont, Jacques Bronner, Sonia Dahan, Paul Marzouk, Pascal Pouedras, Noureddine Djafari, François-Xavier Caroli-Bosc, Jean-François Dessin, Brigitte Gruffat, Armelle Morin-Fatome, Sylvie Thoinet, Bano Konate, Jean-Winoc Decousser, Claire Poyart, Patrick Plessis, Olivier Millet, Vincent Cattoir, Françoise Geffroy, Manica Vasseur, Pierre Carli, Isabelle Citony, Christian Richard, Nicolas Sigur, Patrick Marthelet, Luwawu Mbimba, Pierre Feugier, Philippe Sauder, Hama Djerad, Evelyne Bourgerette, Hanen Chahtour, Adrien Lemaignen, Dominique Bechade, Patrick Ochocki, Antoine Vieillard Baron, Dominique Astruc, Marie-Pierre Moiton, Nicolas Dubois, Sylvie Ledru, Corinne Seknazi, Hélène Poupet, Jean-Philippe Brieux, Gérard Barthélémy, Aihem Yehia, Louis-Jean Couderc, Ahmed, Françoise Rigaux, Yohann N'guyen, Philippe Bethery, Damien Corberand, Etienne Auvray, Paul-Louis Woerther, Christian Combe, Sophie Delesalle, Jean-Marie Piala, Faraj Al Freijat, Philippe Juvin, Malcolm Lemyze, Hyacine Rey, Claire Larible, Noel Milpied, Lémia Zgarni, Julia Gaillard, Agnès Juven, Paola Otean, Adrien Melis, André Pechinot, Olivier Bouchaud, Olivier Chassin, Pierre Hausfater, Asma Trabelsi-Jnifen, Vincent Grobost, Didier Lemery, Pierre Soury, Françoise Brevet, Jacques Tankovic, Dominique Sansot, Jean Louis Salomon, Charlotte Cordonnier, Brigitte Lamy, Antoine Maisonneuve, Dominique Pressac, Claude Rémy, Rodolphe Sobesky, Stéphanie Cognet, Pierre Cougoul, Didier Jan, Dominique Perrotin, Cécile Hombrouk-Alet, Thierry André, Gilbert Pochmalicki, Serge Girard, Vincent Zerr, Guillaume Cadiot, Claudine Lasbasses, Michel Slama, Abderrazak El Yamani, Sophie Brovedani, Jean Armengaud, Romain Hernu, Géraldine Mascade, Aurélien Lorléa'ch, Ali Akkari, Mathieu Tourdjman, Christopher Payan, Eric Jullian, Nathalie Fonsale, Frédéric Riehl, Paul Strock, Geneviève Grise, Philippe Mottaz, Christian Floriot, Marie-Noëlle Ungeheuer, Denis Caillot, Arnaud Chalvon-Demersay, Catherine Branger, Stanislas Bruley des Varannes, Marc Paccalin, Marie-Pierre Danjean, Alexandre Mebazaa, Xavier Brunet, Roland De Varax, Laurence Delhoustal, Sophie Haro, Bruno Chabanon-Pouget, Isabelle Goidin, Dominique Chudersky, Corinne Costes, Delphine Chatellier, Maud Gelez, Damien Dassant, Pascal Joly, Jean-Michel Arnal, Zakaria Hamitou, Philippe Rondepierre, Carole Pignon, Valérie Crombe, Amanda Lopes, Chrystelle Kemenar, Olivia Raulin, Anne-Cécile Hochart, Sandrine Gérart Pons, Valérie Zeller, Guillermo Reyes Ortega, Mathilde Guérin, Audrey Migraine Bouvagnet, Florence Eboue, Isabelle Loury-Lariviere, Sophie Leotard, Suzanne Lima, Marie Kassis, Jean-Luc Donay, Jean-Pierre Audié, Guillaume Cartron, Arnaud Ribier, Fanny Buron, Mirela Tuca, Marius Semenescu, Arnaud Serre, Vincent Quentin, Denise Bouyssou-Destriau, Violaine Bresson, Christine Chandesris Joséphine Chapalain-Cagnon, Eric Cua, Henri Courtade, François Bénézit, Sébastien Lamache, Philippe Bonnefoy, Francis Schneider, Richard Monarchi, Adeline Schendel, Paramasiven Mootien, Ghislaine Gardes, Pierre-François Westeel, Jean-François Magny, François Caron, Jocelyn Michon, Didier Eyer, Isabelle Ronda, Pierre-Yves Robillard, Frédéric Renou, Anna Faucher, Jean-Robert Harlé, Anne Debernardi, Grégory Akerman, Benoît Fontenel, Pierre Hourdebaigt-Larrusse, Marie-Noëlle Adam, Aude Lessene, Abdelkader Hrichi, François Blot, Athéna Le Pierres, Romain Lemarie, Françoise Granier, Véronique Tardy, Marc Gatfosse, Pierre-Marie Roger, François Goupil, Saïd Aberrane, Franck Bernardi, Isabelle Plantier, Nathalie Funakoshi, Jean-Gilles Delecalle, Patricia Barbut, Jacques Reynes, Christophe Roy, Sophie Perreve, Michel Garre, David Ribes, Cyrille Ede, Jean-Claude Dausset, Francis Duchene, Jean Caussin, Michelle Becker-Schneider, Gilles Berthelot, Damien Dupont, Jean-Michel Gillot, Aurélie Messager, Jean-Marie Pannecouck, Jean-Christian Roussel, Alain Reynaud, Sylvie Cariou, Anne Dao, François Guillemot, Martin Martinot, Patrick Casali, Anne-Sophie Poirier, Aissa Kerchache, Necera Sakek, Eric Porthault, Christophe Decoene, Chantal Ache-Papillon, Brigitte Bicais, Jean-Claude Feugier, Thierry Masseron, Charles Marty-Ane, Daniele Goldgran Toledano, Jean-Christophe Dubus, Damien du Cheyron, Dominique Decré, Jean-Loup Pennaforte, Ahmed Tigaizin, Bernard Vache, Eric Oswald, Claire Moulinoux, Anne-Christine Jaouen, Caroline Charlier, Anne-Laure Virlouvet, Ali Kara, Jean-Luc Sicsic, Sylvie Goffart, Mathieu Zuber, Claudine Fèbre, Olivier Lortholary, Mathieu Dupont, Annie Vessieres, Thierry Helvadjian, Thomas Signouret, Cedric Daupin, Sandrine Essouri, Jean-Louis Jacob, Pascal Boileau, Caroline Blazejewski, Quentin Lepiller, Juan-Pablo Maureira, Eddy Lebas, Christophe Deschamps, Amévi Ananivi, Clovis Foguem, Daniel Adoue, Abdourahim Chamouine, Alain Michault, Bruno Guérin, Olivier Baud, Clara Vinci, Thierry Weitten, Jean-Marc Eychene, Marie Froidure, Julien Obiols, Patricia Roussellier, Marc Lecuit, André Cabié, Saskia Foucart, Karim Belhadj, Michel Cingotti, Bruno Dumoulard, Jean Puyhardy, Etienne Danquechin Dorval, Lucile Mendes-Martin, Enrique Casalino, Luc Jarrige, Fabien Lambiotte, Philippe Masson, Mohammed Mansouria, Pierre Thouvenot, Katy Jeannot, Martine Nyunga, Valérie Macci, Florent Masia, Claire Briere de la Hosseraye, Wassila Anteur, André Sommabère, Marie-Claude Germain, Isabelle Arnault, Bernard Carbonelle, Philippe Devos, Daniel Protar, Tiphaine Gaillart, Ludovic Lassel, Laurence Hamou-Plotkine, David Trystram, Thierry Bureau, Olivier Collard, Fanny Vuotto, Sophie Malhiere, Frederique Canis, Gillles Plainfosse, Catherine Lechiche, Bertrand Lassere, Martine Chouraqui, Jean Baptiste Michot, Fethi Radhouane-Khanjari, Carole Barbier, Pascal Bonitchi, Abdelaziz Benkhelil, Odile Salmon, Laurent Damaj Gandhi, Bertrand Minguet, Michel Wagner, Odile Falguières, Zahr-Eddine Ali Chaouche, Eric Zaoui, Isabelle Guichard, Bernard Huttin, Apollinaire Karirisi, Gaël Cinquetti, Christophe Plane, Lionel Rostaing, Yanne Henry-Andrieu, Daniel Re, Virginie Verrier, Pascal Bolot, Michel De Biasi, Laurence Vrigneaud, Mathilde Turpin, Marie-Claude Demachy, Etienne Roussel, Michèle Blancs, Olivier Join-Lambert, Yves Ville, Thierry Granger, Gilles Hilbert, Virginie Medeau, Daniel Villers, Benoit Pilmis, François Gouraud, Emmanuel Ardiet, Catherine Heyraud-Blanchet, Alain Devidas, Hélène Dieye, Julie Cremniter, Jean-François Bergmann, Rozenn Le Berre, Virginie Leguen, Daniel Royer, Gilles Le Maout, Christian Harou, Sylvie Gabriel-Soléan, Yves Regouby, Martine Pestel-Caron, Patrick Brunet, David Boutoille, Emmanuelle Bonnin, Patrice Coulon, Marc Sullice, Marianne Barbieux, Gilles Cambonie, Joëlle Tricoire, Marie-Nadège Bachelier, Delphine Briend, Céline Ramanantsoa, Nathalie Bednarek, Didier Lebreton, Julien Lagrandeur, Damien M'Bey, Philippe Audeguy, Elie Saliba, Lena Damaj, Hassan Fallouh, Pascal Couturier, Fabrice Prévost, Yves Domart, Marie-Odile Lafforgue, Anne Le Du, C. Beuscart, Pierre Guillet, Fabrice Larrazet, Marie-Hélène Hausermann, Henri Robert, Nicolas Fanjaud, François Goehringer, Thomas Bachelot Philippe Badia, Jean-Michel Coulaud, Cristel Fissore Magdelein, Renaud Defebvre, Anne-Sohie Moreau, Johan Courjon, Gilles Salles, Michel Mialon, Silvia Iacobelli, Emmanuelle Bille, Marie-Christine Barbier, Yves Aubard, Patrice Badila, Jean-Philippe Rasigade, Alban Deroux, Evelyne Lecaillon-Thibon, Michel Godin, Abdelmajid Djeffal, Viorica Badurescu, Meriem Canitrot, Pierre Blanchard, Antoine Legros, Laurence Got, Françoise Duluc, Mylène M. Maury, Gilles Dassieu, Nordine Khodeir, Jean-Marie Duez, Mathieu Morincomme, Jérôme Lacroix, Mathieu Revest, Koffi Blewoussi, Isabelle Barazer, Françoise Poitevin, Camille Seignovert, Stéphanie Honore Bouakline, Anne Heidt, Brigitte Malbruny, Julien Desblache, Christian Cattoen, Eric Jaunait, Bruno Chaminade, Claude Bazin, Jonathan Chelly, Anne Pottier, Alain Schmitt, Alain Tissot, Karim Dadoun, P. Rebattu, Claudine Contamin, Arnaud Guerard, Nathalie Ravet, Sandrine Khalifa-Thellier, Marlène Chatron, Gaëlle Dörr, Hélène Biessy, Emmanuel Forestier, Bruno Devaux, Jean-Jacques Grelaud, Xavier Tchenio, Marie-Cécile Ploy, Jérémie Violette, Michèle Burdin, Lionel Falchero, Dominique Jacomy, Jean-Christophe Rozé, Damien Labarriere, Stéphane Leroux, Corinne Meregnani, Assia Ferhat Carre, Paul Orode, Jean-Gabriel Paul, Catherine Godon, Agnès Vinay, Régine Barraduc, Dominique Dallay, Alexandre Ampère, Anne-Gaelle Kervegant, Guillaume Louart, Dominique Beal Ardisson, Francoise Leonetti, Jean-Yves Baril, Stéphanie Haiat, Bincy Darre, Jérôme Bay, Yvan Gauthier, Sylvie Radenne, Pierre-Yves Gueugniaud, Philippe Ravaud, Luc Landraud, Guillaume Ranchon, Loïc Chimot, Véronique Duval, Ilhem Agha-Mir, Sabine Camiade, Estelle Wafo, Jean-Patrick Laporte, Mariam Roncato-Saberane, Camille Bron, Patrice Laudat, Samir Kennouche, Nawel Afroukh, Dominique Neri, Hakim Kherouf, Yoar Hichri, Pierre-Edouard Bollaert, Gwenaelle Vary, Denis Castaing, Christine Lefort, Sébastien Rouget, René Robert, Christelle Guillet-Caruba, Catherine Simonin, Alain Vighetto, Severine Cabasson, Alain Brusset, Alexandra Doloy, Christel Cherlet, Ahmed Rouidi, Marina Salvucci, Réginald Pordes, René-Gilles Patrigeon, Emmanuelle Dupre-Narlet, Jacques Minet, Fethi Taleb, Anne-Marie Colingorski, Tahar Hadou, Sylvain Diamantis, Isabelle Glorieux, Thierry May, Jean-Claude Colombani, Anne Berth-Farges, Nicole Desplaces, Renaud de Tayrac, Elisabeth Walter, Fabienne Lorge, Pascal Reboul, Nathalie Dournon, Laurence Estépa, Marie-Lina Toubia, Mathilde Flahault, Thierry Delacour, Dominique Hurel, Hélinoro Andriamaneo, Cécile Bébéar, Denis Grasset, Miloud Serier, Oléna Orléva, Nadine Dubroca, Hervé Gentilhomme, Jean-Luc Baudel, Isabelle Lavenu, Salim Smati, Carlo Saroufim, Eric Placidi, Albert Sotto, Benoît Libeau, Hélène Leroy, François Golfier, Christophe Dollon, Laurence Desnoulez, Eric Barre, Daniel Cohen, Pascal Priollet, Thierry Marsepoil, Benoît Lionnet, Jacques Tebib, Pascale Penn, Antoine Bouissou, Christian Roth, Olivier Martinet, Anna Schmitt, Nathalie Fruleux, Fouzia Radaoui, Jean-Marc Lessinger, Virginie Morando, Jean-Jacques Maillet, Christophe Fruchart, François Boué, François Goffinet, Franck Lellouche, Martin Demarchi, Alain Geissler, Jean-Charles Picaud, David Assouline, Patricia Brazille, Philippe Guimier, Marie-Françoise Dabysing, Bruno Delpeuch, Vanessa Tran, Guy Gengembre, Delphine Deligne, Dominique Vodovar, Yvan Touze, Sabrina Parent, Anne Decoster, Camille Dewitte, Emmanuel Weiss, Thierry Lambert, Thomas Guimard, Vincent Caille, Claude Guérin, Françoise Evreux, Geneviève Barjon, Basile Ondze, Damien Fournier, Olivia Bandin, Sophie Mignart, Henri Demontclos, Didier Perez, Jacques Croize, Nicole Desbois-Nogard, Guenièvre Imbert, Clarisse Dupin, Khalid Ridah, Marie-Christine Varin, Guillaume Arlet, Edith De Clareuil, Marie-Line Eustache, Patricia Le Pimpec, Louise Fortin, Eugène Ngami, Fabrice Mihout, Cecilia Esnault, Vincent Bouden, Véronique Annaix, Yves Poinsignon, Aurélien Lorchleac'h, Jean-Marc Degreff, Marie Garofano, Renaud Mesnage, Anne-Marie Roque-Afonso, Alain Chevailler, Stéphane Hominal, Thierry Charbonnier, Adrianna Bildea, Fabien Fily, Benjamin Davido, Emmanuel Rassiat, Assi Assi, Stéphanie Brunet, Hervé Jacquier, Catherine Claise, Annie Durand, Yannick Monceau, Pierre Blanc, Jean-Marie Sire, Yves Sucin, Jean-Pierre Zarski, Nathalie Bronet, Ingrid Lafon, Philippe Rey, Jacques Markarian, Eric Sennevile, Olivier Wink, Guilène Barnaud, Anne-Sophie Peultier, Sabine Taylor, Rim Savatier, Patrick Valayer, Claude Negrier, Selim Jennane, Edouard Begon, Laura Hyerle, Delphine Bridoux, Claire Daurel, Benoît Dalle, Mathilde Lescat, Philippe Stolidi, Elodie Perrodeau, Xavier Heches, Pierre Castelnau, Philippe Bray, Jean-Claude Texier, Serge Rossignol, Maud Brung-Lefebvre, Jean-François Subra, Jean-Marie Delarbre, Morgane Schneerson, Guyro Jang, Mona Mehri, Nathalie Landgraf, Pierre-Marie Girard, Armand Goll, Zaineb Bekguesmia, Christophe Clement, Michel Collet, Vincent Maze, Amine Benjelloul, Solène Durliat-Ellie, Vincent Letouzey, François Schmitt, Valérie Martinez, Sarah Watson, Abderrezak Bouasria, François Barbier, Raphael Lauretta, Mirana Razafimahery, Cristina Sirbu, Patrick Malherbe, Anne Wuillai, Ludovic Lesecq, Philippe Gaudard, Serge Houssaye, Jacques Monsegu, Gilles Rival, Chantal Chaplain, Jean-Didier Grangé, Oana Zamfiri, Florence Nguyen-Khac, Marc Portneuf, Jean-Michel Pawlotsky, Delphine Bonnet, Laurent Traissac, Sophie Hamon-Charles, Didier Dreyfuss, Louis Bernard, Laurence Detourmignies, Olivier Martineau, François Pettinelli, Marc Zandecki, Michel Dreyfus, Alain Chapelle, Sébastien Sabbat, Anne-Sophie Labussiere, Jean-Louis Gaillard, Chloé Plouzeau-Jayle, Patrick Zoveda, Véronique Leflon, Marie Levy, Aurélie Labé, Bruno Soulie, Raoul Jacques Bensaude, Hecham Moussa, Sylviane Catteu, Nathalie Biron, Loïc Masson, Georges Mourad, Nejla Aissa, Dragos Ciocan, Hubert De Boysson, Jean-Luc Bouyer, Patrick Yeni, Thierry-Pascal Zame, Caroline Thomas, François Cavalié, Laurence Koulmann, Christophe Rioux, Olivier Barraud, François Bricaire, Marguerite Le Poulain, Marie-Noelle Noulard, René Thomas, Guy Semet, Laurent Mosser, Olivier Marret, Brigitte Rivière, Vincent Jarlier, Jean-Philippe Coindre, Marc Villemain, Martin Pierre, Yacine Benkaci, Philippe Chiron, Hoang Vu-Thien, Jérôme Gournay, Andrea Labaune-Kiss, Brigitte Lauzanne, Fanny Lemercier, Souad Silhadi, Imad Kansau, Christophe Poncelet, Olivier Baldesi, Francis Thuet, Olivier Leroy, Aurore Lamberet, Camille Petit Hoang, Sophie Micheli, Ayman Abokasem, Hakima Nesrine, Pierre Lureau, Christian Chidiac, Vincent Piriou, Fabien Zoulim, Dieudonné Nicobaharaye, Anne Tixier, Isabelle Matheron, Soumeth Abasse, Victoria Cacheux, Serge Herson, Christine Fuhrmann, Olivier Proost, Bernard Bedock, Olivier Rogeaux, Mostapha Hajjar, Anne Reverseau, René Courcol, Françoise Carmagnol, Yves Guénard, Céline Ménard, Bouchra Lamia, Bruno Lemmens, Damien Bouhour, L. Lequen, Gaëlle Baty, Cédric Bouet, Dominique Guerrot, Stéphane Blanc, Catherine Chirouze, Anne-Hélène Reboux, A. Vachée, Gregory Taurin, Myriam Mein-Bottini, Jean-Pierre Belot, Alain Lafeuillade, Patricia Gabez-Therou, Philippe Labrousse, Bernard Jarrousse, Philippe Noto, Vincent Brunot, Philippe Condominas, Marion Challier, Béatrice Berçot, Delphine Anuset, Mélanie Daval Cote, François Bernasconi, Y. Costa, Chandrah Goburdhun, Bernard Gressier, Alban Michaud-herbst, Franck Charlier, Moussa Hecham, Luc Boulain, Hélène Corneloup, Alix Greder Belan, Nicolas Boussekey, Claire-Antoinette Dupuy, Yannick Rouquet, Benoit Renard, Benifla Jl, Etienne Javouhey, Michèle Granier, Marie-Christine Jaffarbandjee, Emilie Piet, Benoît Bergues, Claire Malbrunot, Catherine Tiry, Philippe Mérigot, Mouna Ben Soltana, Chantal Roure Sobas, Florian Radenac, Yves Thomas, Agathe Blaise, Sylvie De Martino, Laurence Legout, Gabriel Choukroun, Jean-François Muir, Peggy Dupretz, Patrick Dupont, François Guichart, Julie Jean, Jean-Michel Descamps, Bernard Kittschke, Anne Gruson, Gerard Viquesnel, Marie Keller, Pascal Chavanet, Françis Vallet, Yvan Vaschalde, Jean-Luc Hanouz, Gerard Lina, Françoise Loison, Simon Vincent, Jean-Paul Thellier, Moncef Afi, Dominique Zagozda, Hélène Sokeng-Affoule, Marc Le Bideau, Jean-François Loriferne, Alain Gravet, Sophie Deprecq, Tarik Naceur, Severine Mielczarek, René-Jean Bensadoun, Bernard Karkous, Yves Bléher, Jocelyne Poulain, Véronique Goulet, Laurence Nicolet, Sophie Arista, Antônio Lúcio Teixeira, Jean-François Schved, Laurent Nicolet, Claire Lecomte, Faiza Benddif-Fin, Michel Aumersier, Laurence Burc-Struxiano, Maxime Thouvenin, Samia Harbi, Mathieu Detave, Catherine Rebeyrotte, Jean-Paul Kisterman, Bruno Berdin, Pascal Vincent, Laurent Argaud, Elisabeth Parisi-Duchene, Geneviève Julienne, Fernanda Farto-Bensasson, Georges-Fabrice Blum, Sad Gaizi, Tali-Anne Szwebel, Raphaël Lepeule, Marie-Thérèse Climas, Anne-Françoise Dillies, Amar Boudhane, Umberto Simeoni, Pierre-François Dequin, Gérard Oliviero, Alain Gourlaouen, Caroline Piau, Marie-France Lutz-Murphy, Benoît Claude, Jean-Paul Aubry, Nadine Dubosc-Marchenay, Kamilla Chraibi, Emmanuelle Heusse, Sylvain Le Chevallier, Nathalie Brieu, Farid Sifaoui, Lorraine Letranchant, Hélène Durox, Jean-Pierre Lagasse, Adel Ghedira, Xavier Roubert, Fatma Magdoud, Hélène Jean-Pierre, Etienne Carbonelle, Olivier Dereeper, Lionel Carbillon, Christophe Billy, Mélanie Roblin, Marie-José Kodzin, Philippe Niel, Solène Makdessi, Matteo Vassallo, Maryse Archambaud, Fabian Haccourt, Didier Blaise, Stéphane Bourgeois, Elena Marcu, Charles Kubiak, Brisse Castel, François Guinet, Marie Pouzoullic, Frédérique Nathan-Bonnet, Vincent Gendrin, Céline Becherrawy, Aline Secher, Pierre Abgueguen, Clarence Eloy, Jean-Marc Tourani, Frédéric Klapczynski, Bernard Montmasson, Philippe Real, Joanna Pofelski, Yves Welker, Karim Krechiem, Eric Caumes, Martine Elena-Daumas, Christophe Saigne, Gilles Hittinger, Chantal Delesalle, Jonathan Messika, Fabrice Lesage, Daniela Pop, Daniel Coetmeur, Renato Colamarino, Chetaou Mahaza, Patrick Plésiat, Isabelle Fredenucci, Mylène Baret, Guy Mager, Pascale Chavel, Isabelle Labourdette, Anne-Claude Menguy, Nicolas Fortineau, Ludovic Le Sec, Valérie Gauduchon, Francis Barraud, Nicolas Letellier, Didier Vincent, Janine Frey, Philippe Riegel, Michel Pavic, Jean-Luc Fabre, Jean-Pierre Fauchart, Alain Goudeau, Stéphanie Husson-Wetzel, Philippe Eymerit, Mohamed Camara, Nathalie Seta, Elisabeth Carole Ngo Bell, Philippe Repellin, Laurent Alric, Vincent Leroy, Françoise Delisle Mizon, Jean-Philippe Emond, Marie-Françoise Borie, Lise Crémet, Wladimir Chelle, Elisabeth Brottier-Mancini, Bernard Garrigues, Claire Letellier, Loïc Geffray, Frédéric Méchaï, Julien Bador, Benoit Guery, Alain-Charles Fouilhoux, Corinne Dagada, Pierre Duhaut, Julien Goustille, Arnaud Sément, Francis Carcenac, Isabelle Girard-Buttaz, Claire Chapuzet, Fabienne Jouatte, Bruno Riou, Fabrice Hayoun, Chloé Di Meglio, Youssef Ali, Michel Leneveu, Nathalie Montagne, Yves Garcera, Audrey Moustache, Pierre-Eric Danin, Geneviève Le Lay, Dominique Courouge-Dorcier, Isabelle Worcel, Emmanuel Morelon, Vincent Pestre, Jean-Pierre Vilque, Jean-Christophe Paquet, Lucien Bodson, Anne-Marie Forest, Fabrice Pierre, Christian Pommier, Fabien Dutasta, Pierre Fournel, Stéphanie Courtois, Elodie Dubois, Serge Vanden Einjden, Patrick Honderlick, Pascal Richette, Fabienne Tamion, Véronique Chassy, Richard Megbemado, Anne-Marie Le Reste, Bernard Simian, Henri Osman, Anthony Texier, Badih Ayach, François Simon, Jean-Michel Filloux, Béatrice Dubourdieu, Jean-Claude Semet, Sarah Kubab, Tawfiq Henni, Patrick Dudeffant, Delphine Hequet, Olivier Mimoz, Marc Auburtin, Amélie Chabrol, Mickael Bonnan, Caroline Léonnet, Claire Wintenberger, Serge Ilunga, Patrice Lanba, Sophie Rosello, Alexandre Damage, Flore Bouche, Michel Thibault, Frederic Faibis, Chantal Dhennain, Jean-Philippe Talarmin, Armelle Lamour, Remi Boussier, Fabien Garnier, Marie-Laure Brival, Nourredine Hedjem, Philippe Vande-perre, Raphaël Coint, Jean-Claude Reveil, Eva Weinbronn, Emmanuelle Lavalard, Alexandra Fille, Françoise Le Turdu, Lionel Leroux, Jean-Yves Lefrant, Jean Berthet, Radia Bouaziz, Alain Ravaud, Sylvaine Rousseau, Yacine Merrouche, Alain Le Coustumier, Bertrand Guider, Gisèle Dewulf, Jean-Marc Faucheux, Jacques Piquet, Franck Leibinger, Charles Cerf, Robin Stephan, Jean-Philippe Redonnet, Jean-Paul Stahl, Ella Dzeing, Simona Pavel, Guy Vernet, Ghada Hatem, Samer Kayal, Jacques Deschamps, Dominique Descamps, Marion Levast, Marc Bouiller, Sylvie Dargere, Claire Dingremont, Stéphane Gaudry, François Maillot, Sylvie Odent, Nathalie Cervantes, Hélène Zanaldi, Laurence Gachassin, Olivier Ruyer, David Patin, Benoît Cazenave, Pascal Jacquier, Michelle Boyer, Béatrice Berteaux, Virginie Zarrouk, Jacques Bor, Isabelle Legoff, Hélène Albinet, Florence Rousseau, Gilles Pialoux, Guenaelle Salaun-Beretta, Alexandra Moura, Véronique Vernet Garnier, Didier Lepelletier, Pierre-Alexandre Hauss, Joëlle Belaisch-Amart, Didier Lepeletier, Jacob Xavier, Aline Nare, Annie Motard-Picheloup, Alain Améri, Bertrand Lioger, Jean-Valère Malfuson, Centre d'infectiologie Necker-Pasteur [CHU Necker], Institut Pasteur [Paris] (IP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre National de Référence Listeria - National Reference Center Listeria (CNRL), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre collaborateur de l'OMS Listeria / WHO Collaborating Centre Listeria (CC-OMS / WHO-CC), Institut Pasteur [Paris] (IP)-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Pierre et Marie Curie - Paris 6 - UFR de Médecine Pierre et Marie Curie (UPMC), Université Pierre et Marie Curie - Paris 6 (UPMC), Département de Médecine interne [Lariboisière], Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Biologie des Infections - Biology of Infection, Service de Gynécologie et Obstétrique [Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Investigation Clinique et d’Accès aux Ressources Biologiques (Plate-forme) - Clinical Investigation and Access to BioResources (ICAReB), Institut Pasteur [Paris] (IP), Infectious Disease Department [Saint Maurice], Agence Nationale de la Santé Publique [Saint-Maurice] (ANSP), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Paris 5 (UPD5), CHU Amiens-Picardie, Mécanismes physiopathologiques et conséquences des calcifications vasculaires - UR UPJV 7517 (MP3CV), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, MONALISA study group, Programme Hospitalier Recherche Clinique, Institut Pasteur, Inserm, French Public Health Agency., ROZIER, marie-Claire, CHU Necker - Enfants Malades [AP-HP], Centre National de Référence Listeria - Biologie des Infections (CNRL), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre collaborateur de l'OMS Listeria - Biologie des Infections (CCOMS), CHU Pitié-Salpêtrière [APHP], Hôpital Lariboisière-Université Paris Diderot - Paris 7 (UPD7), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Cochin [AP-HP], Institut Pasteur [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Centre National de Référence Listeria - Biologie des Infections ( CNRL ), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre collaborateur de l'OMS (CCOMS) des Listeria ( CCOMS ), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité ( CRESS (U1153 / UMR_A 1125) ), Institut National de la Recherche Agronomique ( INRA ) -Université Sorbonne Paris Cité ( USPC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Pierre et Marie Curie - Paris 6 - UFR de Médecine Pierre et Marie Curie ( UPMC ), Université Pierre et Marie Curie - Paris 6 ( UPMC ), Université Paris Diderot - Paris 7 ( UPD7 ) -Hôpital Lariboisière, Biologie des Infections, Institut Pasteur [Paris]-Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Investigation Clinique et d’Accès aux Ressources Biologiques (Plate-forme) - Clinical Investigation and Access to BioResources ( ICAReB ), Agence Nationale de la Santé Publique [Saint-Maurice] ( ANSP ), Assistance Publique - Hôpitaux de Paris, Assistance publique - Hôpitaux de Paris (AP-HP), Université Paris Descartes - Paris 5 ( UPD5 ), Institut Pasteur [Paris]-CHU Necker - Enfants Malades [AP-HP], Institut Pasteur [Paris]-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)

Subjects
Bacteremia/epidemiology/mortality, 0301 basic medicine, Male, Pediatrics, bacteraemia, Infectious Disease Transmission, [SDV]Life Sciences [q-bio], Bacteremia, France/epidemiology, Infant, Newborn, Diseases, Foodborne Diseases, Meningoencephalitis, Pregnancy, Risk Factors, Vertical, Medicine, Listeriosis, Prospective Studies, Pregnancy Complications, Infectious, Prospective cohort study, ddc:618, diabetes, alcoholism, Hazard ratio, Foodborne Diseases/microbiology, immuno suppressive therapies, Prognosis, 3. Good health, [SDV] Life Sciences [q-bio], Hospitalization, Infectious Diseases, isolates, Population Surveillance, Female, France, Listeria monocytogenes/classification/isolation & purification, Cohort study, Adult, medicine.medical_specialty, 030106 microbiology, Notifiable disease, Listeriosis/diagnosis/epidemiology/microbiology, Context (language use), macromolecular substances, 03 medical and health sciences, Humans, study, Aged, [ SDV ] Life Sciences [q-bio], business.industry, Public health, cirrhosis, Infant, Newborn, Infant, Diseases/epidemiology/microbiology, HIV, Mandatory Reporting, Newborn, medicine.disease, Listeria monocytogenes, infection, Infectious Disease Transmission, Vertical, Pregnancy Complications, Infectious/epidemiology/microbiology, Meningoencephalitis/epidemiology/microbiology/mortality, Observational study, business, prognostic, mellitus
Abstract

International audience; Evidence before this study We searched PubMed on June 30, 2016, for English-language cohort studies published since Jan 1, 1980, of patients with invasive listeriosis worldwide with the keywords " listeria " , " listeriosis " , " maternal " , and " neurolisteriosis ". Studies had to include epidemiological or clinical data on listeriosis. All clinical forms of infection were included (bacteraemia, neurolisteriosis, and maternal–neonatal infection). Host risk factors for listeriosis have been well identified, but the clinical features and prognostic factors of the disease are based on retrospective studies compiling heterogeneous data or random collected cases. Furthermore, no clinical trial has ever been done and medical management is not evidence based. Added value of the study Our study is the first prospective clinical study focusing on all forms of invasive listeriosis. The study is based on a national mandatory system that allowed the nearly complete capture of microbiologically proven cases. The study shows a higher burden of listeriosis than reported before: more than 80% of infected mothers experienced major fetal or neonatal complications (fetal loss, very high prematurity, early or late onset disease); only 39% of patients with neurolisteriosis survived and fully recovered. The study provides important new data to improve management and predict outcome in listeriosis, such as determination of the time window for fetal losses (

Published
2016
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47. Increased Time Exposure to Tenofovir Is Associated with a Greater Decrease in Estimated Glomerular Filtration Rate in HIV Patients with Kidney Function of Less than 60 ml/min/1.73 m2

Author

P. Dellamonica, V. Rahelinirina, Christian Pradier, Pascal Pugliese, O. Moranne, Eric Cua, V. Mondain, C. Fafin, V. Esnault, Jacques Durant, Pierre-Marie Roger, Eric Rosenthal, C. Ceppi, I. Perbost, and F. De Salvador

Subjects
Male, medicine.medical_specialty, Time Factors, Anti-HIV Agents, Organophosphonates, Urology, Renal function, HIV Infections, Kidney Function Tests, Risk Factors, Indinavir, medicine, Humans, Tenofovir, Univariate analysis, business.industry, Adenine, Confounding, General Medicine, Middle Aged, medicine.disease, Standard error, Blood pressure, Nephrology, Cohort, Kidney Failure, Chronic, Female, business, Glomerular Filtration Rate, medicine.drug, Kidney disease
Abstract

Tenofovir (TDF), atazanovir (ATAZ) and indinavir (IND) have been reported as possible risk factors for incident chronic kidney disease (CKD) in HIV-infected patients. We investigated the relationship between the duration of antiretroviral exposure and estimated glomerular filtration rate (eGFR) evolution in CKD patients. In a cohort of 1,750 HIV-infected patients, we identified 121 CKD patients with a mean follow-up of 44 ± 35 months. The relationship between mean eGFR at baseline, eGFR slope and time exposure to antiretroviral treatment as well as confounding factors were investigated using a joint modeling procedure. Seventy (58%), 30 (25%) and 33 patients (27%), with a mean age of 50.3 ± 11.7 years, mean eGFR at baseline of 53.0 ± 0.8 (ml/min/1.73 m2) and eGFR slope of 0.46 ± 0.07 ml/min/1.73 m2/year, were exposed to TDF, ATAZ and IND, respectively. In univariate analysis, hepatitis C virus infection, decreased nadir of log CD4 count, high blood pressure at baseline, angiotensin-converting enzyme inhibitor treatment and greater time exposure to TDF during follow-up were associated with a higher slope, whereas greater time exposure to IND was associated with a lower slope. In multivariate analysis, higher TDF time exposure was still significantly associated with eGFR decline, with a dose-effect relationship (slope ± standard error of the mean: 1.1 ± 0.1, 0.5 ± 0.1, –0.07 ± 0.08 and –0.87 ± 0.06 ml/min/1.73 m2/year for no time exposure

Published
2012
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48. Audit of antibiotic therapy used in 66 cases of endocarditis

Author

Pierre Dellamonica, E. Bernard, Pierre-Marie Roger, Eric Cua, Elisa Demonchy, and Céline Pulcini

Subjects
Adult, Male, Methicillin-Resistant Staphylococcus aureus, Pediatrics, medicine.medical_specialty, medicine.drug_class, Antibiotics, Administration, Oral, Nice, Inappropriate Prescribing, Comorbidity, Hospitals, University, Streptococcal Infections, Humans, Medicine, Endocarditis, Medical prescription, Infusions, Intravenous, Aged, Retrospective Studies, computer.programming_language, Infectious Disease Medicine, Medical Audit, business.industry, Retrospective cohort study, Endocarditis, Bacterial, Middle Aged, Staphylococcal Infections, medicine.disease, Drug Utilization, Anti-Bacterial Agents, Treatment Outcome, Infectious Diseases, Infective endocarditis, Practice Guidelines as Topic, Female, Gentamicin, France, Guideline Adherence, business, Hospital Units, computer, medicine.drug
Abstract

Objectives We wanted to assess the quality of antibiotic therapy prescribed for infective endocarditis in our ward. Design We conducted a retrospective audit of all adult patients with endocarditis hospitalized over a 3-year period in the Infectious Diseases Unit of the Nice University Hospital, France. The quality of antibiotic therapy was assessed using the 2004 European Society of Cardiology guidelines as a reference. Antibiotic therapy was considered as appropriate only if the five following items complied with guidelines: antibiotic, dose, route, interval of administration, and duration of antibiotic treatment. Results Sixty-six patients were included, 63 years of age on average. Antibiotic therapy complied with guidelines in 14% of the cases. The most frequent causes of inappropriate therapy were: gentamicin prescribed as a single daily dose in 55% (27/49) of the cases, unnecessary prescriptions of rifampin in 72% (18/25) of the cases, and too long duration of gentamicin course for staphylococcal endocarditis in 32% (9/28) of the cases. Antibiotic therapy was switched from intravenous to oral route in 29% of the patients (n = 19), 18 ± 9 days after starting therapy on average. These endocarditis were mainly left-sided (n = 12) and/or complicated (n = 15). There was no significant association between mortality and inappropriate antibiotic therapy (14% if inappropriate vs. 22%, P = 0.62) or between mortality and oral switch (0% if oral switch vs. 21%, P = 0.052). Conclusions Infective endocarditis antibiotic treatment rarely complied with the 2004 European guidelines, but this did not have a negative impact on mortality. Switching antibiotic therapy from intravenous to oral route was common, even for complicated left-sided endocarditis, and was associated with a favorable outcome in all cases.

Published
2011
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49. Examens paracliniques et durée de l’antibiothérapie des infections ostéoarticulaires

Author

Pierre-Marie Roger, Pierre Dellamonica, Pascal Boileau, Christophe Trojani, V. Lesbats, Eric Cua, and R. Farhad

Subjects
Gynecology, medicine.medical_specialty, Infectious Diseases, business.industry, Antibiotic therapy, medicine, business, Antibacterial agent
Abstract

Resume Les modalites de suivi des infections osteo-articulaires (IOA) sont controversees, notamment quant a l’interet des examens paracliniques. Depuis 2005 nous avons systematise la duree d’antibiotherapie des IOA a six semaines pour tous les patients. Les examens biologiques et iconographiques realises durant l’antibiotherapie ne participent donc pas a la decision d’arret therapeutique. Cette approche doit permettre d’apprecier l’interet de ces examens. Patients et methodes Tous les patients presentant une IOA de juillet 2005 a juillet 2008 et ayant beneficie de six semaines d’antibiotherapie et d’examens paracliniques ( C-reactive protein [CRP], VS, scanner et/ou IRM) etaient inclus. Une CRP inferieure a 10 mg/L et une VS a la premiere heure inferieure a 15 mm etaient considerees comme normales. Les donnees radiologiques etaient interpretees par un radiologue referent en IOA avec un enregistrement systematique des parametres pertinents. Resultats Quatre-vingt-sept patients presentant une IOA avaient beneficie d’une duree moyenne d’antibiotherapie de 42 ± 0,3 jours. La guerison etait observee chez 82 patients (94 %) avec un recul de 36 ± 9 mois, cinq presentant une rechute. La CRP, disponible dans 71 cas en fin d’antibiotherapie, etait normale dans 44/68 evolutions favorables (65 %) et dans deux tiers des evolutions defavorables. La VS, disponible dans 22 cas en fin d’antibiotherapie, etait normale dans huit evolutions favorables (32 %). En fin d’antibiotherapie, le scanner montrait une infection active dans 18/27 evolutions favorables (67 %), l’IRM suggerant ce meme diagnostic dans 10/16 cas (63 %). Conclusion CRP et VS sont peu informatives pour le suivi therapeutique des IOA. De meme, les examens radiologiques sont inoperants pour determiner la duree d’antibiotherapie.

Published
2011
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50. Évaluation des pratiques professionnelles, tableau de bord et bon usage de l’antibiothérapie au cours des pneumonies aiguës communautaires

Author

M.-H. Schiano, R. Farhad, Pierre-Marie Roger, S. Rancurel, Céline Pulcini, E. Bernard, F. De Salvador, and Eric Cua

Subjects
Computerized databases, Gynecology, medicine.medical_specialty, business.industry, Treatment outcome, Professional practice, Surgery, Clinical Practice, Infectious Diseases, Lung disease, Antibiotic therapy, medicine, business, Beta lactam antibiotics, Antibacterial agent
Abstract

Resume L’evaluation des pratiques professionnelles (EPP) comporte trois phases : la mise en evidence de dysfonctionnements dans les pratiques medicales, des mesures correctives puis l’evaluation des ajustements induits. Notre objectif est de montrer qu’un tableau de bord (TB) est un outil pertinent pour realiser une EPP. Patients et methode Notre TB enregistre chaque hospitalisation, incluant 24 parametres dont le diagnostic et l’antibiotherapie. Utilisant le TB, la premiere phase d’EPP a revele une heterogeneite non justifiee des modalites therapeutiques des pneumonies aigues communautaires (PAC). La deuxieme phase a consiste en l’ecriture de notre protocole therapeutique, visant a reduire les fluoroquinolones (FQ) et les cephalosporines de troisieme generation (C3G). Nous rapportons ici la troisieme phase d’EPP, utilisant le TB pour evaluer l’application du protocole. Resultats Les PAC representaient 250 hospitalisations avant le protocole (octobre a janvier 2005, 2006 et 2007) et 113 apres (octobre 2008 au 30 mars 2009). La conformite avec le protocole etait augmentee de la premiere a la seconde periode : 58 % versus 69 %, p = 0,045. L’utilisation inadequate des FQ et/ou des C3G etait plus frequente durant la premiere periode, comparativement a la seconde : 49 % versus 38 %, p = 0,048. La duree d’hospitalisation etait plus longue avant (9 ± 5 jours) qu’apres l’application du protocole (7 ± 4 jours), p = 0,009. Une evolution defavorable etait observee dans respectivement 15/250 (6 %) et 3/113 cas ( Conclusion Un TB permet l’execution rapide de deux des trois phases de l’EPP et participe a l’appropriation du protocole, la reduction des FQ et des C3G etant sans impact sur la morbi-mortalite.

Published
2010
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