Dual Therapy in HIV Patients in 4 Days a Week Versus 7 Days a Week

Summary

The trial is an open-label, multicenter, prospective, randomized trial in 2 parallel groups, evaluating at W48 the non inferiority of antiretroviral dual therapy taken 4 consecutive days per week versus antiretroviral dual therapy 7/7 days per week in HIV-1 infected patients with controlled viral load under antiretroviral dual therapy.

Timeline

Start

2021-06-21

Primary completion

2023-07

Completion

2024-07

Outcome

Missed primary endpoint

paper Virological failure occurred in eight (4%) of 219 participants in the 4/7-days group and none of 214 in the 7/7-days group (adjusted difference of 3·7%, 95% CI 1·2-6·2). PMID 42140217 ↗

paper The per-protocol analysis yielded a similar result (3·7%, 95% CI 1·2-6·3), meaning that non-inferiority was not demonstrated. PMID 42140217 ↗

Publications

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• Background Ferry JA, Sohani AR, Longtine JA, Schwartz RA, Harris NL. HHV8-positive, EBV-positive Hodgkin lymphoma-like large B-cell lymphoma and HHV8-positive intravascular large B-cell lymphoma. Mod Pathol. 2009 May;22(5):618-26. doi: 10.1038/modpathol.2009.36. Epub 2009 Mar 13.
• Background Ho JE, Hsue PY. Cardiovascular manifestations of HIV infection. Heart. 2009 Jul;95(14):1193-202. doi: 10.1136/hrt.2008.161463. No abstract available.
• Background Edelman EJ, Gordon KS, Glover J, McNicholl IR, Fiellin DA, Justice AC. The next therapeutic challenge in HIV: polypharmacy. Drugs Aging. 2013 Aug;30(8):613-28. doi: 10.1007/s40266-013-0093-9.
• Background Flandre P, Raffi F, Descamps D, Calvez V, Peytavin G, Meiffredy V, Harel M, Hazebrouck S, Pialoux G, Aboulker JP, Brun Vezinet F. Final analysis of the Trilege induction-maintenance trial: results at 18 months. AIDS. 2002 Mar 8;16(4):561-8. doi: 10.1097/00002030-200203080-00007.
• Background Bowersox J. ACTG 343: three drugs better than two for maintaining HIV suppression. NIAID AIDS Agenda. 1998 Mar:1-2, 10-1.
• Background Arribas JR, Girard PM, Landman R, Pich J, Mallolas J, Martinez-Rebollar M, Zamora FX, Estrada V, Crespo M, Podzamczer D, Portilla J, Dronda F, Iribarren JA, Domingo P, Pulido F, Montero M, Knobel H, Cabie A, Weiss L, Gatell JM; OLE/RIS-EST13 Study Group. Dual treatment with lopinavir-ritonavir plus lamivudine versus triple treatment with lopinavir-ritonavir plus lamivudine or emtricitabine and a second nucleos(t)ide reverse transcriptase inhibitor for maintenance of HIV-1 viral suppression (OLE): a randomised, open-label, non-inferiority trial. Lancet Infect Dis. 2015 Jul;15(7):785-92. doi: 10.1016/S1473-3099(15)00096-1. Epub 2015 Jun 7.
• Background Perez-Molina JA, Rubio R, Rivero A, Pasquau J, Suarez-Lozano I, Riera M, Estebanez M, Palacios R, Sanz-Moreno J, Troya J, Marino A, Antela A, Navarro J, Esteban H, Moreno S; GeSIDA 7011 Study Group. Simplification to dual therapy (atazanavir/ritonavir + lamivudine) versus standard triple therapy [atazanavir/ritonavir + two nucleos(t)ides] in virologically stable patients on antiretroviral therapy: 96 week results from an open-label, non-inferiority, randomized clinical trial (SALT study). J Antimicrob Chemother. 2017 Jan;72(1):246-253. doi: 10.1093/jac/dkw379. Epub 2016 Sep 13.
• Background Di Giambenedetto S, Fabbiani M, Quiros Roldan E, Latini A, D'Ettorre G, Antinori A, Castagna A, Orofino G, Francisci D, Chinello P, Madeddu G, Grima P, Rusconi S, Di Pietro M, Mondi A, Ciccarelli N, Borghetti A, Foca E, Colafigli M, De Luca A, Cauda R; Atlas-M Study Group. Treatment simplification to atazanavir/ritonavir + lamivudine versus maintenance of atazanavir/ritonavir + two NRTIs in virologically suppressed HIV-1-infected patients: 48 week results from a randomized trial (ATLAS-M). J Antimicrob Chemother. 2017 Apr 1;72(4):1163-1171. doi: 10.1093/jac/dkw557.
• Background Pulido F, Ribera E, Lagarde M, Perez-Valero I, Palacios R, Iribarren JA, Payeras A, Domingo P, Sanz J, Cervero M, Curran A, Rodriguez-Gomez FJ, Tellez MJ, Ryan P, Barrufet P, Knobel H, Rivero A, Alejos B, Yllescas M, Arribas JR; DUAL-GESIDA-8014-RIS-EST45 Study Group. Dual Therapy With Darunavir and Ritonavir Plus Lamivudine vs Triple Therapy With Darunavir and Ritonavir Plus Tenofovir Disoproxil Fumarate and Emtricitabine or Abacavir and Lamivudine for Maintenance of Human Immunodeficiency Virus Type 1 Viral Suppression: Randomized, Open-Label, Noninferiority DUAL-GESIDA 8014-RIS-EST45 Trial. Clin Infect Dis. 2017 Nov 29;65(12):2112-2118. doi: 10.1093/cid/cix734.
• Background Llibre JM, Hung CC, Brinson C, Castelli F, Girard PM, Kahl LP, Blair EA, Angelis K, Wynne B, Vandermeulen K, Underwood M, Smith K, Gartland M, Aboud M. Efficacy, safety, and tolerability of dolutegravir-rilpivirine for the maintenance of virological suppression in adults with HIV-1: phase 3, randomised, non-inferiority SWORD-1 and SWORD-2 studies. Lancet. 2018 Mar 3;391(10123):839-849. doi: 10.1016/S0140-6736(17)33095-7. Epub 2018 Jan 6.
• Background Katlama C, Assoumou L, Valantin MA, Soulie C, Martinez E, Beniguel L, Bouchaud O, Raffi F, Molina JM, Fellahi S, Peytavin G, Marcelin AG, Kolta S, Capeau J, Gibowski S, Cardon F, Reynes J, Costagliola D; members of the ANRS 163 ETRAL study. Dual therapy combining raltegravir with etravirine maintains a high level of viral suppression over 96 weeks in long-term experienced HIV-infected individuals over 45 years on a PI-based regimen: results from the Phase II ANRS 163 ETRAL study. J Antimicrob Chemother. 2019 Sep 1;74(9):2742-2751. doi: 10.1093/jac/dkz224.
• Background Joly V, Burdet C, Landman R, Vigan M, Charpentier C, Katlama C, Cabie A, Benalycherif A, Peytavin G, Yeni P, Mentre F, Argoud AL, Amri I, Descamps D, Yazdanpanah Y; LAMIDOL Study Group. Dolutegravir and lamivudine maintenance therapy in HIV-1 virologically suppressed patients: results of the ANRS 167 trial (LAMIDOL). J Antimicrob Chemother. 2019 Mar 1;74(3):739-745. doi: 10.1093/jac/dky467.
• Background Taiwo BO, Marconi VC, Berzins B, Moser CB, Nyaku AN, Fichtenbaum CJ, Benson CA, Wilkin T, Koletar SL, Colasanti J, Acosta EP, Li JZ, Sax PE. Dolutegravir Plus Lamivudine Maintains Human Immunodeficiency Virus-1 Suppression Through Week 48 in a Pilot Randomized Trial. Clin Infect Dis. 2018 May 17;66(11):1794-1797. doi: 10.1093/cid/cix1131.
• Background van Wyk J, Ajana F, Bisshop F, De Wit S, Osiyemi O, Portilla Sogorb J, Routy JP, Wyen C, Ait-Khaled M, Nascimento MC, Pappa KA, Wang R, Wright J, Tenorio AR, Wynne B, Aboud M, Gartland MJ, Smith KY. Efficacy and Safety of Switching to Dolutegravir/Lamivudine Fixed-Dose 2-Drug Regimen vs Continuing a Tenofovir Alafenamide-Based 3- or 4-Drug Regimen for Maintenance of Virologic Suppression in Adults Living With Human Immunodeficiency Virus Type 1: Phase 3, Randomized, Noninferiority TANGO Study. Clin Infect Dis. 2020 Nov 5;71(8):1920-1929. doi: 10.1093/cid/ciz1243.
• Background Cahn P, Madero JS, Arribas JR, Antinori A, Ortiz R, Clarke AE, Hung CC, Rockstroh JK, Girard PM, Sievers J, Man C, Currie A, Underwood M, Tenorio AR, Pappa K, Wynne B, Fettiplace A, Gartland M, Aboud M, Smith K; GEMINI Study Team. Dolutegravir plus lamivudine versus dolutegravir plus tenofovir disoproxil fumarate and emtricitabine in antiretroviral-naive adults with HIV-1 infection (GEMINI-1 and GEMINI-2): week 48 results from two multicentre, double-blind, randomised, non-inferiority, phase 3 trials. Lancet. 2019 Jan 12;393(10167):143-155. doi: 10.1016/S0140-6736(18)32462-0. Epub 2018 Nov 9.
• Background Dybul M, Chun TW, Yoder C, Hidalgo B, Belson M, Hertogs K, Larder B, Dewar RL, Fox CH, Hallahan CW, Justement JS, Migueles SA, Metcalf JA, Davey RT, Daucher M, Pandya P, Baseler M, Ward DJ, Fauci AS. Short-cycle structured intermittent treatment of chronic HIV infection with highly active antiretroviral therapy: effects on virologic, immunologic, and toxicity parameters. Proc Natl Acad Sci U S A. 2001 Dec 18;98(26):15161-6. doi: 10.1073/pnas.261568398. Epub 2001 Dec 4.
• Background Dybul M, Nies-Kraske E, Dewar R, Maldarelli F, Hallahan CW, Daucher M, Piscitelli SC, Ehler L, Weigand A, Palmer S, Metcalf JA, Davey RT, Rock Kress DM, Powers A, Beck I, Frenkel L, Baseler M, Coffin J, Fauci AS. A proof-of-concept study of short-cycle intermittent antiretroviral therapy with a once-daily regimen of didanosine, lamivudine, and efavirenz for the treatment of chronic HIV infection. J Infect Dis. 2004 Jun 1;189(11):1974-82. doi: 10.1086/386344. Epub 2004 May 10.
• Background Cohen CJ, Colson AE, Sheble-Hall AG, McLaughlin KA, Morse GD. Pilot study of a novel short-cycle antiretroviral treatment interruption strategy: 48-week results of the five-days-on, two-days-off (FOTO) study. HIV Clin Trials. 2007 Jan-Feb;8(1):19-23. doi: 10.1310/hct0801-19.
• Background Cohen C, Colson A, Pierone G. The FOTO study: Twenty-Four week results support the safety of a two day break on efavirenz-based antiretroviral therapy. Presented at: Ninth International Congress on Drug Therapy in HIV Infection; November 8-13, 2008; Glasgow, UK
• Background Cohen C, Colson A, Pierone G, et al. The FOTO study: The 48 week extension to assess durability of the strategy of taking efavirenz, tenofovir and emtricitabine Five days On, Two days Off (FOTO) each week in virologically suppressed patients. Presented at: Fifth International AIDS Society Conference on HIV Pathogenesis, Treatment, and Prevention; July 19-22, 2009; Cape Town, South Africa
• Background Reynolds SJ, Kityo C, Hallahan CW, Kabuye G, Atwiine D, Mbamanya F, Ssali F, Dewar R, Daucher M, Davey RT Jr, Mugyenyi P, Fauci AS, Quinn TC, Dybul MR. A randomized, controlled, trial of short cycle intermittent compared to continuous antiretroviral therapy for the treatment of HIV infection in Uganda. PLoS One. 2010 Apr 22;5(4):e10307. doi: 10.1371/journal.pone.0010307.
• Background Leibowitch J, Mathez D, de Truchis P, Ledu D, Melchior JC, Carcelain G, Izopet J, Perronne C, David JR. Four days a week or less on appropriate anti-HIV drug combinations provided long-term optimal maintenance in 94 patients: the ICCARRE project. FASEB J. 2015 Jun;29(6):2223-34. doi: 10.1096/fj.14-260315. Epub 2015 Apr 1.
• Background BREATHER (PENTA 16) Trial Group. Weekends-off efavirenz-based antiretroviral therapy in HIV-infected children, adolescents, and young adults (BREATHER): a randomised, open-label, non-inferiority, phase 2/3 trial. Lancet HIV. 2016 Sep;3(9):e421-e430. doi: 10.1016/S2352-3018(16)30054-6. Epub 2016 Jun 20.
• Background de Truchis P, Assoumou L, Landman R, Mathez D, Le Du D, Bellet J, Amat K, Katlama C, Gras G, Bouchaud O, Duracinsky M, Abe E, Alvarez JC, Izopet J, Saillard J, Melchior JC, Leibowitch J, Costagliola D, Girard PM, Perronne C; ANRS 162-4D Study Group. Four-days-a-week antiretroviral maintenance therapy in virologically controlled HIV-1-infected adults: the ANRS 162-4D trial. J Antimicrob Chemother. 2018 Mar 1;73(3):738-747. doi: 10.1093/jac/dkx434.
• Background R. Landman, P. De Truchis, L. Assoumou, S. Lambert, K. Amat, J. Bellet, B. Lefebvre, C. Allavena, C. Katlama, Y. Yazdanpanah, J.-M. Molina, A. Gelley, S. Gibowski, J.-C. Alvarez, L. Morand-Joubert, D. Costagliola, P.-M. Girard, ANRS 170 QUATUOR study group -ANRS 170 QUATUOR 4/7 days maintenance strategy in antiretroviral treated adults with HIV-1 infection: an open randomised parallel non-inferiority phase III trial Abstract IAS2019 WEAB0406LB
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• Background Zehnacker L, Abe E, Mathez D, Alvarez JC, Leibowitch J, Azoulay S. Plasma and Intracellular Antiretroviral Concentrations in HIV-Infected Patients under Short Cycles of Antiretroviral Therapy. AIDS Res Treat. 2014;2014:724958. doi: 10.1155/2014/724958. Epub 2014 Nov 9.
• Landman R, Assoumou L, Lambert-Niclot S, Amat K, Katlama C, Allavena C, Lacombe K, Bouchaud O, Liegeon G, Ghosn J, Gibowski S, Alvarez JC, Abe E, Capeau J, Fellahi S, Barkat S, Parienti JJ, Morand-Joubert L, De Truchis P; ANRS-177 DUETTO study group. Short-cycle 4-days-per-week maintenance two-drug therapy in people living with HIV (ANRS-177 DUETTO): a randomised, open-label, multicentre, non-inferiority trial. Lancet HIV. 2026 Jun;13(6):e380-e391. doi: 10.1016/S2352-3018(26)00012-3. Epub 2026 May 15.

Drugs

Evaluation	Drug	Modality	Dose	Route
Subject	Darunavir	Small molecule	800 mg	—
Subject	Dolutegravir	Other / unclassified	50 mg	—
Subject	Lamivudine	Other / unclassified	300 mg	—
Subject	Rilpivirine	Small molecule	25 mg	—

Indications