Switch Study to Evaluate Dolutegravir Plus Lamivudine in Virologically Suppressed Human Immunodeficiency Virus Type 1 Positive Adults (TANGO)

Summary

The aim of the study is to establish if human immunodeficiency virus type 1 (HIV-1) infected adult participants with current virologic suppression on a \>=3-drug tenofovir alafenamide (TAF) based regimen (TBR) remain suppressed upon switching to a two-drug regimen of dolutegravir (DTG) 50 milligram (mg) + lamivudine (3TC) 300 mg. This study will also provide important information regarding the safety and participant satisfaction with this two-drug regimen. The primary objective of this trial is to demonstrate the non-inferior antiviral activity of switching to DTG + 3TC once daily compared to continuation of TBR over 48 weeks in HIV-1 infected, antiretroviral therapy (ART)-experienced, virologically suppressed participants. This study also will characterize the long-term antiviral activity, tolerability and safety of DTG + 3TC compared to TBR through Week 144 and characterize the long-term antiviral activity, tolerability and safety of DTG + 3TC through Week 200. This will be a 200-week, Phase III, randomized, open-label, active-controlled, multicenter, parallel- group study. The study will include a screening phase (up to 28 days), a randomized early switch phase (Day 1 up to Week 148), a randomized late switch phase (Week 148 up to Week 200), and a continuation phase (post Week 200). HIV-1 infected adults on stable TBR will be randomized 1:1 to switch to DTG + 3TC once daily for up to 200 weeks, or to continue their TBR for 148 weeks, at which time and if HIV-1 ribonucleic acid (RNA) \<50 copies per milliliter (c/mL) at Week 144, these participants will switch to DTG + 3TC up to Week 200.

Timeline

Start

2018-01-18

Primary completion

2019-05-20

Completion

2022-05-03

Publications

• 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.
• Scholten S, Cahn P, Portilla J, Bisshop F, Hodder S, Ruane P, Kaplan R, Wynne BR, Man CY, Grove R, Wang R, Jones B, Ait-Khaled M, Kisare M, Okoli C. Dolutegravir/Lamivudine Efficacy and Safety Outcomes in People With HIV-1 With or Without Historical Resistance Results at Screening: 48-Week Pooled Analysis. Open Forum Infect Dis. 2024 Jul 1;11(7):ofae365. doi: 10.1093/ofid/ofae365. eCollection 2024 Jul.
• Ait-Khaled M, Oyee J, Ooi AYR, Wynne B, Maldonado A, Jones B, Wang T. Efficacy and Safety of Switching to Dolutegravir/Lamivudine Versus Continuing a Tenofovir Alafenamide-Based Regimen in Virologically Suppressed Adults With Human Immunodeficiency Virus Type 1: Subgroup Analysis of Participants With Elvitegravir as Baseline Third Agent From the TANGO Study. Open Forum Infect Dis. 2024 May 2;11(5):ofae227. doi: 10.1093/ofid/ofae227. eCollection 2024 May.
• Chandasana H, Singh R, Adkison K, Ait-Khaled M, Pene Dumitrescu T. Population pharmacokinetic modeling of dolutegravir/lamivudine to support a once-daily fixed-dose combination regimen in virologically suppressed adults living with HIV-1. Antimicrob Agents Chemother. 2024 May 2;68(5):e0150423. doi: 10.1128/aac.01504-23. Epub 2024 Apr 8.
• Walmsley S, Smith DE, Gorgolas M, Cahn PE, Lutz T, Lacombe K, Kumar PN, Wynne B, Grove R, Bontempo G, Moodley R, Okoli C, Kisare M, Jones B, Clark A, Ait-Khaled M. Efficacy and safety of switching to dolutegravir/lamivudine in virologically suppressed people with HIV-1 aged >/= 50 years: week 48 pooled results from the TANGO and SALSA studies. AIDS Res Ther. 2024 Mar 21;21(1):17. doi: 10.1186/s12981-024-00604-9.
• Wang R, Underwood M, Llibre JM, Bernal Morell E, Brinson C, Sanz Moreno J, Scholten S, Moore R, Saggu P, Oyee J, Moodley R, Wynne B, Kisare M, Jones B, Ait-Khaled M. Very-Low-Level Viremia, Inflammatory Biomarkers, and Associated Baseline Variables: Three-Year Results of the Randomized TANGO Study. Open Forum Infect Dis. 2023 Dec 9;11(1):ofad626. doi: 10.1093/ofid/ofad626. eCollection 2024 Jan.
• Batterham RL, Espinosa N, Katlama C, McKellar M, Scholten S, Smith DE, Ait-Khaled M, George N, Wright J, Gordon LA, Moodley R, Wynne B, van Wyk J. Cardiometabolic Parameters 3 Years After Switch to Dolutegravir/Lamivudine vs Maintenance of Tenofovir Alafenamide-Based Regimens. Open Forum Infect Dis. 2023 Jul 12;10(7):ofad359. doi: 10.1093/ofid/ofad359. eCollection 2023 Jul.
• Wang R, Wright J, Saggu P, Ait-Khaled M, Moodley R, Parry CM, Lutz T, Podzamczer D, Moore R, Gorgolas Hernandez-Mora M, Kinder C, Wynne B, van Wyk J, Underwood M. Assessing the Virologic Impact of Archived Resistance in the Dolutegravir/Lamivudine 2-Drug Regimen HIV-1 Switch Study TANGO through Week 144. Viruses. 2023 Jun 11;15(6):1350. doi: 10.3390/v15061350.
• Osiyemi O, De Wit S, Ajana F, Bisshop F, Portilla J, Routy JP, Wyen C, Ait-Khaled M, Leone P, Pappa KA, Wang R, Wright J, George N, Wynne B, Aboud M, van Wyk J, Smith KY. Efficacy and Safety of Switching to Dolutegravir/Lamivudine Versus Continuing a Tenofovir Alafenamide-Based 3- or 4-Drug Regimen for Maintenance of Virologic Suppression in Adults Living With Human Immunodeficiency Virus Type 1: Results Through Week 144 From the Phase 3, Noninferiority TANGO Randomized Trial. Clin Infect Dis. 2022 Sep 29;75(6):975-986. doi: 10.1093/cid/ciac036.
• van Wyk J, Ait-Khaled M, Santos J, Scholten S, Wohlfeiler M, Ajana F, Jones B, Nascimento MC, Tenorio AR, Smith DE, Wright J, Wynne B. Brief Report: Improvement in Metabolic Health Parameters at Week 48 After Switching From a Tenofovir Alafenamide-Based 3- or 4-Drug Regimen to the 2-Drug Regimen of Dolutegravir/Lamivudine: The TANGO Study. J Acquir Immune Defic Syndr. 2021 Jun 1;87(2):794-800. doi: 10.1097/QAI.0000000000002655.

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