Supplementary webappendix

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1 Supplementary webappendix This webappendix formed part of the original submission and has been peer reviewed. We post it as supplied by the authors. Supplement to: Chéret A, Nembot G, Mélard A, et al, for the OPTIPRIM ANRS Study Group. Intensive five-drug antiretroviral therapy regimen versus standard triple-drug therapy during primary HIV-1 infection (OPTIPRIM-ANRS 147): a randomised, open-label, phase 3 trial. Lancet Infect Dis 2015; published online Feb org/ /s (15)

2 OPTIPRIM Scientific Committee Brigitte Autran, Marie-Laure Chaix, Antoine Chéret, Sandrine Couffin-Cadiergues, Cécile Goujard, Bruno Hoen, Alain Lafeuillade, Caroline Lascoux-Combe, Camille Lécuroux, Annie Le Palec, Yann Mazens, Laurence Meyer, Georges Nembot, Daniel Olive, Gianfranco Pancino, Isabelle Ravaux, Christine Rouzioux, Assia Samri, Asier Saez-Cirion, Juliette Saillard, Bruno Spire, Catherine Tamalet, Jean-Marc Tréluyer, Alain Venet. Study OPTIPRIM-ANRS 147 sites CHRU Saint-Jacques (Besançon) - Service de Médecine Interne B. Hoen, C. Bourdeaux Hôpital de Bicêtre (Paris) - Service de Médecine Interne et Maladies Infectieuses J.F. Delfraissy, C. Goujard, I. Amri, E. Fourn, Y. Quertainmont, M. Môle Hôpital Lariboisière (Paris) - Service de Médecine Interne A. Rami, A. Durel, M. Diemer, M. Parrinello CHR Aix en Provence - Service d'hématologie Oncologie T. Allègre Hôpital Font-Pré (Toulon) - Service d'infectiologie A. Lafeuillade, G. Hittinger, V. Lambry, M. Carrerre, G.Philip Institut Pasteur - Centre Médical C. Duvivier, P.H. Consigny, C. Charlier, M. Shoai, F. Touam Hôpital Tenon (Paris) - Service des Maladies Infectieuses G. Pialoux, L. Slama, T. L Yavanc, P. Mathurin, A. Adda, V. Berrebi Hôpital Cochin (Paris) - Département de Médecine Interne D. Salmon, E. Chakvetadze, T. Tassadit, E. Ousseima, M.P. Pietri Hôpital Henri Mondor (Paris) - Service d'immunologie Clinique Y. Levy, A.S. Lascaux, J. D. Lelievre, M Giovanna, S. Dominguez, C. Dumont Hôpital Pitié Salpétrière (Paris) - Service des Maladies Infectieuses et Tropicales C. Katlama, M.A. Valentin, S. Seang, L. Schneider, N. Kiorza, A. Chermak, S. Ben Abdallah Hôpital Pitié Salpétrière (Paris) - Service de Médecine Interne A. Simon, F. Pichon, M. Pauchard Hôpital Saint-Louis (Paris) - Service des Maladies Infectieuses J.M. Molina, C. Lascoux, D. Ponscarme, N. Colin De Verdiere, A. Scemla, N. De Castro, Rachline, Garrait, w. Rozenbaum, S. Ferret, S. Balkan, F. Clavel, M. Tourdjman, M. Lafaurie, A. Aslan J. Goguel, S.M. Thierry, V. De Lastours, S. Gallien, J. Pavie, J. Delgado, C. Mededji, R. Veron Hôpital P. Zobda Quitman (Fort de France) - Service des Maladies Infectieuses et Tropicales S. Abel, S. Pierre- François, C. Baringhton CHU Angers - Service des Maladies Infectieuses et Tropicales J.M. Chennebault, Y.M. Vandamme, P.Fialaire, S. Rehaiem, V. Rabier, P. Abgueguen Hôpital Saint André (Bordeaux) - Service de Médecine Interne et Maladies Infectieuses P. Morlat, M.A. Vandenhende, N. Bernard, D. Lacoste, C. Michaux, F. Paccalin, M.C. Receveur, S. Caldato, J. Delaune Hôpital Pellegrin (Bordeaux) - Service des Maladies Infectieuses et Tropicales J.M. Ragnaud, D. Neau, L. Lacaze- Buzy Hôpital Edouard Herriot (Lyon) - Service d'immunologie Clinique J.M. Livrozet, F. Jeanblanc, D. Makhloufi, F. Brunel Dalmas, J.J Jourdain, P. Chiarello Hôpital Bichat Claude Bernard (Paris) - Service des Maladies Infectieuses et Tropicales P. Yeni, B. Phung, C. Rioux, C. Godard, F. Louni, N. El Alami Talbi, G. Catalano, F. Guiroy Hôpital Gui de Chauliac (Montpellier) - Service des Maladies Infectieuses et Tropicales J. Reynes, J.M. Jacquet, V. Fauchere, C. Merle. V. Lemoine, M. Loriette, Morquin, A. Makinson, N. Atoui, C. Tramoni Hôtel Dieu (Nantes) - Service d'infectiologie F. Raffi, C. Allavena, B. Bonnet, S. Bouchez, N. Feuillebois, C. Brunet-François, V. Reliquet, O. Mounoury, P. Morineau-Le-Houssine, E. Billaud, D. Brosseau, H. Hüe Hôpital de l'archet 1 (Nice) - Service des Maladies Infectieuses et Tropicales P. Dellamonica, M. Vassallo, A. Leplatois, J. Durant, A. Naqvi, A. Joulié. Hôpital Pontchaillou (Rennes) - Service des Maladies Infectieuses F. Souala, C. Michelet, C. Arvieux, P. Tattevin, H. Leroy, M. Revest, F. Fily, J.M. Chapplain, C. M. Ratajczak Hôpital Bretonneau (Tours) - Service de Médecine Interne et Maladies Infectieuses G. Gras, L. Bernard, J.F. Dailloux, V. Laplantine Hôpital Purpan (Toulouse) - Service des Maladies Infectieuses et Tropicales L. Cuzin, B. Marchou, S. Larrigue, M. Chauveau, F. Balsarin, M. Obadia

3 Hôpital G. Dron (Tourcoing) - Service Universitaire régional des Maladies Infectieuses et du Voyageur - A. Chéret, S. Bonne, T. Huleux, F. Ajana, I. Alcaraz, V. Baclet, H. Melliez, N. Viget, X. De La Tribonniere, E. Aissi, J. Poissy Hôpital de la Conception (Marseille) - Service des Maladies Infectieuses - I. Ravaux, A. Vallon, M. Varan Hôpital de Brabois (Nancy) - Service des Maladies Infectieuses et Tropicales - T. May, L. Letranchant, C. Burty, A. Briaud, S. Wassoumbou, M. Stenzel, M.P. Bouillon CHU Charles Nicolle (Rouen) - Hôpital de Jour Maladies Infectieuses et Tropicales - Y. Debab, F. Caron, I. Gueit, C. Chapuzet, F. Borsa Lebas, M. Etienne Hôpital de la Croix Rousse (Lyon) - Service des Maladies Infectieuses P. Miailhes, T. Perpoint, A. Senechal, I. Schlienger, L. Cotte, C. Augustin Normand, A. Boibieux, T. Ferry, N. Corsini, E. Braun, J. Lippran, F. Biron, C. Chidiac, S. Pailhes, J. Lipman, E. Braun, J. Koffi, V. Thoirain, C. Brochier Hôpital Mignot (Le Chesnay) ) - Service des Maladies Infectieuses et Tropicales - A. Greder Belan, A. Therby, S. Monnier, M. Ruquet Centre Hospitalier Intercommunal (Créteil) - Service de Médecine Interne - V. Garrait, L. Richier Hôpital La Grave (Toulouse) - Service de Dermatologie et Médecine Sociale - F. Prevoteau Du Clary Hôpital Ambroise Paré (Marseille) Dispensaire - P. Philibert, C. Chapus Centre hospitalier Universitaire de Fort de France (Martinique)-Service de Maladies Infectieuses-A. Cabié, S. Abel.

4 Inclusion criteria Age 18 years at the screening visit Patients with acute or recent primary HIV-1 infection - Acute infection defined by the presence of negative or weakly positive HIV-1 ELISA, with negative or incomplete HIV-1 Western blot ( 1 antibody) and positive HIV RNA and/or positive Ag p24. - Recent infection defined by the presence of positive HIV-1 ELISA with incomplete HIV-1 Western blot ( 2 and < 5 antibodies with the presence of anti-p24 antibody associated with antigp160 or anti-gp120 or anti-gp41 antibody) and positive HIV RNA. Symptomatic primary infection or CD4 < 500/mm3. Inclusion within 10 weeks following the date of diagnosis of primary HIV infection. Free, informed and written consent signed by the patient and the investigator at the latest on the day of screening and before any examination required by the trial. Patient covered by French national health insurance. Patients participating in ancillary virological and immunological studies must be followed in a centre chosen to participate in these studies and must accept the additional sampling constraints. Exclusion criteria Patient with an isolated HIV-2 viral strain. Patient who has received prophylactic antiretroviral therapy after exposure to HIV during the 6 months preceding inclusion. Woman of childbearing potential not using effective contraception (IUCD and condom). Pregnant woman or nursing mother. AIDS-defining opportunistic infection apart from oesophageal candidiasis. Patient with HBs antigen. Decompensated cirrhosis (Child-Pugh stage B and C). Neoplastic disease currently treated by chemotherapy and/or radiotherapy. Co-administration of unauthorized treatments ASAT, ALAT or bilirubin 10 times the upper limit of normal PT < 50% Creatinine clearance < 60 ml/min Number of platelet count < 25,000/mm3 Person placed under legal guardianship. Patient participating in another study evaluating other treatments comprising an exclusion period that still applies at the time of screening.

5 Other secondary endpoints Virological and immunological endpoints - Compare HIV DNA levels per million PBMC (estimation of the frequency of infected PBMC), per ml of blood (estimation of the absolute value), and per million CD4 (estimation of the frequency of infected CD4). Compare percentages of patients with HIV DNA < 70 copies/million PBMC at D14, M1, M3, M6, M12, M18, M24 M26 and M30 between the two arms. - In the case of virological failure, estimate the number and type of resistance mutations on protease, reverse transcriptase, and/or integrase genes. Investigate progression to an X4-tropic strain and, in the light of data of the literature, a maraviroc resistance mutation. Clinical endpoints - Progression of HIV infection defined by the development of class B or C clinical events or death between D0 and M30 Other analyses: - Search for predictive markers of HIV DNA levels < 70 copies/million PBMC at M24 - Search for predictive markers of HIV RNA levels after discontinuation

6 Supplementary figure 1: Trial profile post-treatment interruption Month 24 (N=39 ; per protocol analysis) Month 24 (N=43; per protocol analysis) Primary endpoint 2 did not meet treatment interruption criteria 2 did not meet treatment interruption criteria Interruption treatment criteria achieved N=37 Interruption treatment criteria achieved N=41 8 did not accept to interrupt treatment 7 did not accept to interrupt treatment 29 accepted to interrupt treatment at Month accepted to interrupt treatment at Month resumed treatment according to protocol criteria 4 resumed treatment without protocol criteria 9 resumed treatment according to protocol criteria 2 resumed treatment without protocol criteria 10 did not resume until Month did not resume until Month 30

7 Supplementary figure 2: Probability to maintain HIV RNA <400 copies/ml after treatment interruption