1. Efficacy and safety of varenicline for smoking cessation in people living with HIV in France (ANRS 144 Inter-ACTIV): a randomised controlled phase 3 clinical trial
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Patrick Mercié, Julie Arsandaux, Christine Katlama, Samuel Ferret, Aurélie Beuscart, Christian Spadone, Claudine Duvivier, Jacques Reynes, Nathalie Wirth, Laetitia Moinot, Antoine Bénard, David Zucman, Xavier Duval, Jean-Michel Molina, Bruno Spire, Catherine Fagard, Geneviève Chêne, Hélène Allaguy-Salachy, Henri-Jean Aubin, Claudine Bernard-Henry, Claude Beuscart, Anne Borgne, Olivier Bouchaud, Charles Brahmy, Dominique Breilh, André Cabié, Claude Cateland, Antoine Cheret, Sandrine Couffin-Cadiergues, Marie-Dominique Dautzenberg, Pierre Dellamonica, Pascale Denis-Kandel, Christine Denis-Vatant, Michel Detilleux, Michel Dupon, Brigitte El Harrar, Marie Christine Fagnen Sylvaire, Simone Guillermet, Christine Jacomet, Vincent Jeantils, Marek Korzek, Estibaliz Lazaro, Béatrice Le Maitre, Frédéric Lucht, Marianne Maquet, Audrey Mathieu, Thierry May, Sonia Merigeaud, Philippe Morlat, Alissa Naqvi, Didier Neau, Jean Perriot, Sandrine Pierre-François, Isabelle Poizot-Martin, Elisabeth Quoix, Matthieu Rebillard, Caroline Roussillon, Eric Rosenthal, Thierry Sainte-Marie, Dominique Salmon-Céron, Luminita Schneider, Anne Simon, Malika Soussi, Albert Sotto, Anne-Marie Taburet, Elina Teicher, Monique Termote, Valery Trosini-Desert, Renaud Verdon, Jean-Paul Viard, Daniel Vittecoq, Muriel Vray, David Youssi, Service de Médecine Interne et Immunologie Clinique [CHU Bordeaux] (Pôle Médecine Interne), CHU Bordeaux [Bordeaux], Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), CIC Bordeaux, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Service des maladies infectieuses et tropicales [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [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), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), Centre d'infectiologie Necker-Pasteur [CHU Necker], Institut Pasteur [Paris]-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Infection à VIH, réservoirs, diversité génétique et résistance aux antirétroviraux (ARV) (EA 7327), Université Paris Descartes - Paris 5 (UPD5), Université Sorbonne Paris Cité (USPC), 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, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service d’information Médicale [CHU de Bordeaux] (Pôle de Santé Publique), Service de Médecine Interne [Hôpital Foch, Suresnes] (SMI), Hôpital Foch [Suresnes], CIC Bichat [AP-HP, Hôpital Bichat-Claude-Bernard] (CIC 1425 Inserm), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC), Service des Maladies Infectieuses et Tropicales [CHU Saint Louis], Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], 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), 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), ANRS 144 Inter-ACTIV study group : Allaguy-Salachy H, Arsandaux J, Aubin HJ, Bénard A, Bernard-Henry C, Beuscart A, Beuscart C, Borgne A, Bouchaud O, Brahmy C, Breilh D, Cabié A, Cateland C, Chêne G, Cheret A, Couffin-Cadiergues S, Dautzenberg MD, Dellamonica P, Denis-Kandel P, Denis-Vatant C, Detilleux M, Dupon M, Duval X, Duvivier C, El Harrar B, Fagard C, Fagnen Sylvaire MC, Ferret S, Guillermet S, Jacomet C, Jeantils V, Katlama C, Korzek M, Lazaro E, Le Maitre B, Lucht F, Maquet M, Mathieu A, May T, Mercié P, Merigeaud S, Moinot L, Molina JM, Morlat P, Naqvi A, Neau D, Perriot J, Pierre-François S, Poizot-Martin I, Quoix E, Rebillard M, Reynes J, Roussillon C, Rosenthal E, Sainte-Marie T, Salmon-Céron D, Schneider L, Simon A, Soussi M, Sotto A, Spadone C, Spire B, Taburet AM, Teicher E, Termote M, Trosini-Desert V, Verdon R, Viard JP, Vittecoq D, Vray M, Wirth N, Youssi D, Zucman D., Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut National de la Santé et de la Recherche Médicale (INSERM)-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], Institut Pasteur [Paris] (IP)-CHU Necker - Enfants Malades [AP-HP], Centre Médical de l'Institut Pasteur (CMIP), Institut Pasteur [Paris] (IP), Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques et émergentes (TransVIHMI), Institut de Recherche pour le Développement (IRD)-Université de Yaoundé I-Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Maladies Infectieuses et Tropicales [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Dupuis, Christine
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Adult ,Counseling ,Male ,medicine.medical_specialty ,Epidemiology ,medicine.medical_treatment ,Immunology ,Population ,HIV Infections ,Placebo ,Drug Administration Schedule ,law.invention ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Double-Blind Method ,Randomized controlled trial ,law ,Virology ,Internal medicine ,medicine ,Humans ,Nicotinic Agonists ,030212 general & internal medicine ,education ,Varenicline ,education.field_of_study ,030505 public health ,business.industry ,Incidence (epidemiology) ,Smoking ,Odds ratio ,Middle Aged ,3. Good health ,Clinical trial ,Treatment Outcome ,Infectious Diseases ,chemistry ,[SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie ,Smoking cessation ,Female ,[SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie ,France ,0305 other medical science ,business - Abstract
International audience; BACKGROUND:Tobacco smoking is common in people living with HIV, but high-quality evidence on interventions for smoking cessation is not available in this population. We aimed to assess the efficacy and safety of varenicline with counselling to aid smoking cessation in people living with HIV.METHODS:The ANRS 144 Inter-ACTIV randomised, parallel, double-blind, multicentre, placebo-controlled phase 3 trial was done at 30 clinical hospital sites in France. People living with HIV who had smoked at least ten cigarettes per day for 1 year or longer, were motivated to stop smoking, were not dependent on another psychoactive substance, and had no history of depression or suicide attempt were eligible. Using a computer-generated randomisation sequence, we allocated (1:1) the patients to receive either varenicline titrated to two 0·5 mg doses twice daily or placebo twice daily for 12 weeks, plus face-to-face counselling. Patients and investigators were masked to treatment group allocation. Patients who were not abstinent at week 24 were offered open-label varenicline for 12 additional weeks. The primary outcome was the proportion of smokers continuously abstinent from week 9 to week 48. Smoking status was confirmed by carbon monoxide in exhaled air. Primary analyses were done in both the intention-to-treat (ITT) population and modified ITT (mITT) population, which comprised all patients who took at least one tablet of their assigned study treatment. The safety analyses were done in the mITT population. The trial is registered at ClinicalTrials.gov, number NCT00918307. The trial status is complete.FINDINGS:From Oct 26, 2009, to Dec 20, 2012, of 303 patients assessed for eligibility, 248 patients were randomly assigned to the varenicline group (n=123) or the placebo group (n=125). After randomisation, one participant initially assigned to the placebo group was excluded from the ITT analysis for a regulatory reason (no French health-care coverage). 102 patients in the varenicline group and 111 patients in the placebo group received at least one dose of their assigned treatment and were included in the mITT analysis. In the ITT analysis, varenicline was associated with a higher proportion of patients achieving continuous abstinence over the study period (week 9-48): 18 (15%, 95% CI 8-21) of 123 in the varenicline group versus eight (6%, 2-11) of 124 in the placebo group, adjusted odds ratio (OR) 2·5 (95% CI 1·0-6·1; p=0·041). In the mITT analysis, varenicline was also associated with higher continuous abstinence: 18 (18%, 95% CI 10-25) of 102 versus eight (7%, 2-12) of 111 in the placebo group (adjusted OR 2·7, 95% CI 1·1-6·5; p=0·029). The incidence of depression was 2·4 per 100 person-years (95% CI 0·6-9·5; two [2%] of 102) in the varenicline group and 12·4 per 100 person-years (95% CI 6·9-22·5; 11 [10%] of 111) in the placebo group. 14 (7%) of 213 participants had 18 cardiovascular events: six (6%) of 102 people in the varenicline group and eight (7%) of 111 people in the placebo group.INTERPRETATION:Varenicline is safe and efficacious for smoking cessation in people living with HIV and should be recommended as the standard of care.FUNDING:The French National Institute for Health and Medical Research (INSERM)-French National Agency for Research on AIDS and Viral Hepatitis (ANRS) and Pfizer.
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- 2018