Dolutegravir and lamivudine maintenance therapy in HIV-1 virologically suppressed patients: results of the ANRS 167 trial (LAMIDOL)

Joly,; Burdet, Charles; Landman, Roland; Vigan, Marie; Charpentier, Charlotte; Katlama, Christine; Cabie, André; Benalychérif, Aı̈da; Peytavin, Gilles; Yéni, Patrick; Mentré, France; Al, Argoud; Amri, Imane; Descamps, Diane; Yazdanpanah, Yazdan

doi:10.1093/jac/dky467

Cited by 71 publications

(45 citation statements)

References 24 publications

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“…11 In EMERALD, exclusion criteria were less restrictive (and thus participants may be more representative of the real world) than in other recent switch studies for HIV ART. [26][27][28][29][30][31][32][33] While participants in EMERALD were ART experienced, with 58% of participants having received ‡5 previous antiretroviral agents, and 15% had previous VF, few participants had PDVR cumulative through week 48. Subgroup analyses by previous antiretroviral use and VF showed no effect on rebound rates, virologic response, and VF rates by the FDAsnapshot analysis.…”

Section: Discussionmentioning

confidence: 99%

Week 48 Resistance Analyses of the Once-Daily, Single-Tablet Regimen Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (D/C/F/TAF) in Adults Living with HIV-1 from the Phase III Randomized AMBER and EMERALD Trials

Lathouwers

Wong

Brown

et al. 2020

AIDS Research and Human Retroviruses

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Darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) 800/150/200/10 mg is being investigated in two Phase III trials, AMBER (NCT02431247; treatment-naive adults) and EMERALD (NCT02269917; treatmentexperienced, virologically suppressed adults). Week 48 AMBER and EMERALD resistance analyses are presented. Postbaseline samples for genotyping/phenotyping were analyzed from protocol-defined virologic failures (PDVFs) with viral load (VL) ‡400 copies/mL at failure/later time points. Post hoc analyses were deep sequencing in AMBER, and HIV-1 proviral DNA from baseline samples (VL <50 copies/mL) in EMERALD. Through week 48 across both studies, no darunavir, primary PI, or tenofovir resistance-associated mutations (RAMs) were observed in HIV-1 viruses of 1,125 participants receiving D/C/F/TAF or 629 receiving boosted darunavir plus emtricitabine/ tenofovir-disoproxil-fumarate. In AMBER, the nucleos(t)ide analog reverse transcriptase inhibitor (N(t)RTI) RAM M184I/V was identified in HIV-1 of one participant during D/C/F/TAF treatment. M184V was detected pretreatment as a minority variant (9%). In EMERALD, in participants with prior VF and genoarchive data (N = 140; 98 D/C/F/TAF and 42 control), 4% had viruses with darunavir RAMs, 38% with emtricitabine RAMs, mainly at position 184 (41% not fully susceptible to emtricitabine), 4% with tenofovir RAMs, and 21% ‡ 3 thymidine analogassociated mutations (24% not fully susceptible to tenofovir) detected at screening. All achieved VL <50 copies/mL at week 48 or prior discontinuation. D/C/F/TAF has a high genetic barrier to resistance; no darunavir, primary PI, or tenofovir RAMs were observed through 48 weeks in AMBER and EMERALD. Only one postbaseline M184I/V RAM was observed in HIV-1 of an AMBER participant. In EMERALD, baseline archived RAMs to darunavir, emtricitabine, and tenofovir in participants with prior VF did not preclude virologic response.

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Section: Discussionmentioning

confidence: 99%

Week 48 Resistance Analyses of the Once-Daily, Single-Tablet Regimen Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (D/C/F/TAF) in Adults Living with HIV-1 from the Phase III Randomized AMBER and EMERALD Trials

Lathouwers

Wong

Brown

et al. 2020

AIDS Research and Human Retroviruses

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“…The main objectives of the cohort are to assess the virological efficacy of DTG in real clinical practice settings and to assess the overall tolerability of DTG-based regimens. Moreover, the ongoing widespread use of less-drug regimens, following the results from clinical trials, showed promising results of DTG-based two-drug regimen both in treatment-experienced patients and in treatment-naïve subject 20–23. This fact has lead the ODOACRE cohort to focus on assessing the efficacy, safety and tolerability of DTG-based dual regimens (ie, DTG plus either rilpivirine, RPV, or lamivudine, 3TC) in clinical practice.…”

Section: Cohort Descriptionmentioning

confidence: 99%

Cohort profile: The Observational cohort for the study of DOlutegravir in Antiretroviral Combination REgimens (ODOACRE)

et al. 2019

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PurposeThe Observational cohort for the study of DOlutegravir in Antiretroviral Combination REgimens (ODOACRE) cohort was established in Italy in 2016 to evaluate the overall efficacy and tolerability of dolutegravir (DTG)-based antiretroviral (ARV) regimens in clinical practice.ParticipantsThe ODOACRE cohort enrols all adult HIV-1-infected patients, both treatment-naïve and treatment-experienced, starting a DTG-based ARV regimen, in 11 clinical centres in Italy from 2014.Findings to dateIn recent years, various works by the ODOACRE cohort have been produced, demonstrating the high efficacy and tolerability of DTG-based ARV regimens in clinical practice, both in ART-naïve (in the setting of acute HIV-1 infection and late presenters patient) and experienced patients. We confirmed the virological efficacy of DTG-based regimens and we evaluated predictors of virological failure. We investigated cause of discontinuation and evaluated tolerability and metabolic profile of the regimens. Within these investigations, we explored particularly the use of DTG in simplification in two-drug regimen with either rilpivirine or lamivudine. We also compared DTG-based regimens with other integrase inhibitors in clinical practice.Future plansTo continue to study long-term efficacy and tolerability of DTG-based regimens is the purpose of the ODOACRE cohort.

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“…In the GEMINI trials, DTG + 3TC and DTG + TDF/FTC showed similar rapid declines in plasma viral load, regardless of baseline viral load, and no resistance was reported for up to 96 weeks [ 8 , 10 ]. The efficacy and safety of switching to DTG + 3TC in adults suppressed on 3DRs have been demonstrated in smaller studies [ 11 , 12 ]. Here, we present the week 48 primary end-point analysis of the phase 3 TANGO study in which the efficacy and safety of a switch to DTG/3TC FDC in adults living with HIV-1 with virologic suppression on a 3- or 4-drug tenofovir alafenamide (TAF)–based regimen was evaluated.…”

mentioning

confidence: 99%

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

Wyk

Ajana

Bisshop

et al. 2020

Clinical Infectious Diseases

183

192

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Background The 2-drug regimen dolutegravir (DTG) + lamivudine (3TC) is indicated for treatment-naive adults with human immunodeficiency virus type 1 (HIV-1). We present efficacy and safety of switching to DTG/3TC in virologically suppressed individuals. Methods TANGO is an open-label, multicenter, phase 3 study that randomized adults (1:1, stratified by baseline third agent class) with HIV-1 RNA <50 copies/mL to switch to once-daily fixed-dose DTG/3TC or remain on a tenofovir alafenamide (TAF)–based regimen. The primary end point was proportion of participants with HIV-1 RNA ≥50 copies/mL at week 48 (US Food and Drug Administration Snapshot algorithm) in the intention-to-treat–exposed population (4% noninferiority margin). Results 743 adults were enrolled; 741 received ≥1 dose of study drug (DTG/3TC, N = 369; TAF-based regimen, N = 372). At week 48, proportion of participants with HIV-1 RNA ≥50 copies/mL receiving DTG/3TC was 0.3% (1/369) vs 0.5% (2/372) with a TAF-based regimen (adjusted treatment difference [95% confidence interval], −0.3 [−1.2 to .7]), meeting noninferiority criteria. No participants receiving DTG/3TC and 1 receiving a TAF-based regimen met confirmed virologic withdrawal criteria, with no emergent resistance at failure. Drug-related grade ≥2 adverse events and withdrawals due to adverse events occurred in 17 (4.6%) and 13 (3.5%) participants with DTG/3TC and 3 (0.8%) and 2 (0.5%) with a TAF-based regimen, respectively. Conclusions DTG/3TC was noninferior in maintaining virologic suppression vs a TAF-based regimen at week 48, with no virologic failure or emergent resistance reported with DTG/3TC, supporting it as a simplification strategy for virologically suppressed people with HIV-1. Clinical Trials Registration NCT03446573.

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Dolutegravir and lamivudine maintenance therapy in HIV-1 virologically suppressed patients: results of the ANRS 167 trial (LAMIDOL)

Cited by 71 publications

References 24 publications

Week 48 Resistance Analyses of the Once-Daily, Single-Tablet Regimen Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (D/C/F/TAF) in Adults Living with HIV-1 from the Phase III Randomized AMBER and EMERALD Trials

Week 48 Resistance Analyses of the Once-Daily, Single-Tablet Regimen Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (D/C/F/TAF) in Adults Living with HIV-1 from the Phase III Randomized AMBER and EMERALD Trials

Cohort profile: The Observational cohort for the study of DOlutegravir in Antiretroviral Combination REgimens (ODOACRE)

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

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