Portal de Periódicos da CAPES

A 4-days-on and 3-days-off maintenance treatment strategy for adults with HIV-1 (ANRS 170 QUATUOR): a randomised, open-label, multicentre, parallel, non-inferiority trial

2022; Elsevier BV; Volume: 9; Issue: 2 Linguagem: Inglês

10.1016/s2352-3018(21)00300-3

2405-4704

Roland Landman, Pierre de Truchis, Lambert Assoumou, Sidonie Lambert, Jonathan Bellet, Karine Amat, Bénédicte Lefebvre, Clotilde Allavena, Christine Katlama, Yazdan Yazdanpanah, Jean‐Michel Molina, Ventzislava Petrov–Sanchez, Séverine Gibowski, Jean‐Claude Alvarez, Jacques Leibowitch, Jacqueline Capeau, Soraya Fellahi, Martin Duracinský, Laurence Morand‐Joubert, Dominique Costagliola, Pierre‐Marie Girard, Isabelle LAMAURY, Firouzé Bani‐Sadr, Gilles FORCE, Amélie CHABROL, Fabienne CABY, Olivier PATEY, Anne FRESARD, Amandine Gagneux-Brunon, Catherine CHIROUZE, Claudine Duvivier, Jérémie LOURENCO, Violaine TOLSMA, C. Janssen, Nathalie LEROLLE, Pilartxo CATALAN, Agathe RAMI, Lucile DE PONTHAUD, Gilles PICHANCOURT, Safa NASRI, Stéphanie LANDOWSKI, Julie Bottero, Flory MFUTILA KAYKAY, Gilles Pialoux, Olivier Bouchaud, Sophie ABGRALL, Caroline GATEY, Laurence Weiss, Juliette PAVIE, Dominique SALMON-CERON, David Zucman, Jean-Daniel Lelievre, Romain Palich, Anne SIMON, Marie-Caroline MEYOHAS, Julien GRAS, André Cabie, Mathilde PIRCHER, Philippe Morlat, Mojgam HESSAMFAR, Didier Neau, Charles CAZENAVE, Claire GENET, Jean-François FAUCHER, Djamila MAKHLOUFI, André Boibieux, Sylvie BREGIGEON-RONOT, Hélène LAROCHE, Aurélie SAUTEREAU, Jacques REYNES, Alain Makinson, François Raffi, Olivier BOLLENGIER-STRAGIER, Alissa Naqvi, Eric CUA, Eric ROSENTHAL, Cédrick ARVIEUX, Rodolphe BUZELE, David Rey, Marie-Laure BATARD, Louis Bernard, Pierre Delobel, Marie PIFFAUT, Renaud Verdon, Lionel Piroth, Mathieu Blot, Pascale LECLERCQ, Anne Signori-Schmuck, Thomas HULEUX, Agnès Meybeck, Thierry May, Patrick MIAILHES, Thomas PERPOINT, Alix GREDER-BELAN, Brigitte Elharrar, Marie-Aude KHUONG, Marie POUPARD, Laurent BLUM, Christophe Michau, Thierry PRAZUCK, Patrick Philibert, Laurence SLAMA, Hitoto HIKOMBO, Iuliana DARASTEANU, Pierre-Marie GIRARD, Jean‐Claude Alvarez, Dominique Mathez, Pierre DE TRUCHIS, Roland Landman, Jean‐Luc Meynard, Laurence Morand‐Joubert, Sidonie LAMBERT, Damien LE DU, Christian PERRONNE, Lambert Assoumou, Dominique Costagliola, Jean‐Claude Melchior, Martin DURACINSKI, Ventzislava Petrov-Sanchez, Karine Amat, Aı̈da Benalychérif, Babacar Sylla, Ambre GELLEY, Séverine GIBOWSKI, Guillaume Le Meut, Rodolphe THIEBAUT, Nathan Clumeck, Vincent Leclercq, Francesca CECCHERINI-SILBERSTEIN, Laurent DECOSTER, Isabelle LAMAURY, Firouzé Bani‐Sadr, Gilles FORCE, Amélie CHABROL, Fabienne Caby, Olivier PATEY, Anne FRESARD, Amandine Gagneux-Brunon, Catherine Chirouze, Claudine Duvivier, Jérémie LOURENCO, Violaine TOLSMA, C. Janssen, Nathalie LEROLLE, Pilartxo CATALAN, Agathe RAMI, Lucile DE PONTHAUD, Gilles PICHANCOURT, Safa NASRI, Stéphanie LANDOWSKI, Julie Bottero, Flory MFUTILA KAYKAY, Gilles Pialoux, Olivier Bouchaud, Sophie Abgrall, Caroline GATEY, Laurence Weiss, Juliette PAVIE, Dominique SALMON-CERON, David Zucman, Jean‐Daniel Lelièvre, Romain Palich, Anne SIMON, Marie-Caroline MEYOHAS, Julien GRAS, André Cabie, Mathilde Pircher, Philippe Morlat, Mojgam HESSAMFAR, Didier Neau, Charles CAZENAVE, Claire GENET, Jean-François FAUCHER, Djamila MAKHLOUFI, André Boibieux, Sylvie BREGIGEON-RONOT, Hélène LAROCHE, Aurélie SAUTEREAU, Jacques REYNES, Alain Makinson, François Raffi, Olivier BOLLENGIER-STRAGIER, Alissa Naqvi, Eric CUA, Eric ROSENTHAL, Cédrick ARVIEUX, Rodolphe BUZELE, David Rey, Marie-Laure BATARD, Louis Bernard, Pierre Delobel, M Piffaut, Renaud Verdon, Lionel Piroth, Mathieu Blot, Pascale LECLERCQ, Anne Signori-Schmuck, Thomas HULEUX, Agnès Meybeck, Thierry May, Patrick MIAILHES, Thomas PERPOINT, Alix GREDER-BELAN, Brigitte Elharrar, Marie-Aude KHUONG, Marie POUPARD, L. Blum, Christophe Michau, Thierry PRAZUCK, Patrick Philibert, Laurence SLAMA, Hitoto HIKOMBO, Iuliana DARASTEANU, Pierre-Marie GIRARD, Jean‐Claude Alvarez, Dominique Mathez, Pierre de Truchis, Roland Landman, Jean‐Luc Meynard, Laurence MORAND-JOUBERT, Sidonie LAMBERT, Damien LE DU, Christian PERRONNE, Lambert Assoumou, Dominique Costagliola, Jean‐Claude Melchior, Martin DURACINSKI, Ventzislava Petrov–Sanchez, Karine Amat, Aı̈da Benalychérif, Babacar Sylla, Ambre Gelley, Séverine GIBOWSKI, Guillaume Le Meut, Rodolphe THIEBAUT, Nathan Clumeck, Vincent Leclercq, Francesca CECCHERINI-SILBERSTEIN, Laurent DECOSTER,

HIV Research and Treatment

Background Intermittent (on 4 days per week) antiretroviral therapy (ART) for patients with HIV-1 might be more convenient, better tolerated, and cheaper than continuous treatment. We aimed to establish the efficacy and safety of a 4-days-on and 3-days-off (intermittent) maintenance regimen versus a standard 7 day (continuous) maintenance regimen. Methods In a randomised, open-label, multicentre, parallel, non-inferiority trial, we randomly assigned (1:1) adults with HIV-1 infection with a plasma viral load (pVL) of less than 50 copies per mL for more than 12 months and no drug-resistance mutations to either the intermittent regimen or their existing continuous maintenance regimen, with stratification according to third therapeutic agent (protease inhibitor, non-nucleoside reverse transcriptase inhibitor, or integrase-strand transfer inhibitor). Participants were recruited from 59 hospitals throughout France. The main exclusion criteria were CD4 cell count lower than 250 cells per μL and chronic hepatitis B virus infection. The primary endpoint was the proportion of participants in the modified intention-to-treat (mITT) population who started the study strategy presenting treatment success at week 48 (pVL <50 copies per mL without strategy modification), estimated using the US Federal Drug Administration snapshot approach, with a 5% non-inferiority margin. The study was registered with ClinicalTrials.gov (NCT03256422) and EudraCT (2017-000040-17). The trial is now closed. Findings From Sept 7, 2017, to Jan 22, 2018, 850 potential participants were screened for eligibility. 647 participants were enrolled and randomly assigned (1:1) to either the intermittent or the continuous treatment group. The mITT population included 636 participants (318 per group). At week 48, in the mITT population, treatment success was recorded in 304 (96%) of 318 participants in the intermittent treatment group and 308 (97%) of 318 in the continuous treatment group (adjusted difference –1·3%, 95% CI –4·2 to 1·7). Six (2%) participants in the intermittent treatment group and four (1%) participants in the continuous treatment group had virological failure. Grade 3–4 adverse events were reported in 29 (9%) participants in the intermittent treatment group and 39 (12%) participants in the continuous treatment group (p=0·320). Daily life satisfaction improved in 153 (59%) of 258 participants in the intermittent treatment group versus 19 (7%) of 255 in the continuous treatment group (p<0·0001). ART costs were 43% lower in the intermittent treatment group than in the continuous treatment group (p<0·0001). Interpretation These findings show the non-inferiority of the treatment strategy of 4-consecutive-days-on and 3-days-off strategy maintenance regimen relative to standard continuous ART triple therapy over 48 weeks. 4 days on and off treatment represents a workable, effective alternative strategy for patients with high adherence to ART, and using a drug combination with a high genetic barrier to resistance. Funding Institut National de la Santé et de la Recherche Médicale Agence Nationale de Recherche sur le Sida et les Hépatites Virales, Maladies Infectieuses Emergentes.