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

Abstract

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.

Keywords: 2-drug regimen; integrase strand transfer inhibitor; nucleoside reverse transcriptase inhibitor; simplification; virologic suppression.

© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America.

Figures

Figure 1.

Trial profile. aParticipants could have multiple reasons for ineligibility. bThe most common reasons for not meeting inclusion criteria or meeting exclusion criteria are listed. All other reasons occurred in <1% of participants. cOne participant in the TAF–based regimen group was found to be taking a tenofovir disoproxil fumarate–based regimen at baseline and therefore was excluded from the safety population. dProtocol deviations leading to exclusion from the per-protocol population; participants could have had more than 1 reason. Abbreviations: AE, adverse event; ART, antiretroviral therapy; DTG, dolutegravir; HIV-1, human immunodeficiency virus type 1; 3TC, lamivudine; TAF, tenofovir alafenamide.

Figure 2.

A, Virologic outcomes at week 48 in the intention-to-treat–exposed population by US Food and Drug Administration Snapshot algorithm. B, Adjusted treatment differences. aOne fatal adverse event unrelated to study treatment occurred (homicide). bBased on Cochran-Mantel-Haenszel stratified analysis adjusting for baseline third agent class. Abbreviations: 3TC, lamivudine; AE, adverse event; DTG, dolutegravir; HIV-1, human immunodeficiency virus type 1; TAF, tenofovir alafenamide.

Figure 3.

Proportion of participants with HIV-1 RNA

Figure 4.

Change from baseline in homeostasis model assessment–insulin resistance (HOMA-IR) in the safety population. Geometric mean ratio and 95% confidence interval for postbaseline values based on a loge transformation. Change from baseline was calculated using a repeated measures model adjusting for treatment, visit, baseline third agent class, CD4+ cell count (continuous), age (continuous), sex, race, body mass index (continuous), presence of hypertension, loge-transformed baseline HOMA-IR, treatment-by-visit interaction, and baseline value-by-visit interaction, with visit as the repeated factor. Abbreviations: 3TC, lamivudine; CI, confidence interval; DTG, dolutegravir; TAF, tenofovir alafenamide.

Figure 5.

Change from baseline at week 48 in renal biomarkers. aEstimated mean change from baseline at week 48 in each group calculated from mixed model repeated measures adjusting for treatment, visit, baseline third agent class, CD4+ cell count (continuous), age (continuous), sex, race, body mass index (continuous), presence of diabetes mellitus, presence of hypertension, baseline biomarker (continuous), treatment-by-visit interaction, and baseline value-by-visit interaction, with visit as the repeated factor. bBased on estimated geometric means ratio of week 48 vs baseline. Based on the same model as plasma/serum markers except adjusting for loge-transformed baseline biomarker (continuous). *P < .001. Abbreviations: 3TC, lamivudine; CKD-EPI, Chronic Kidney Disease Epidemiology Collaboration equation; DTG, dolutegravir; eGFR, estimated glomerular filtration rate; TAF, tenofovir alafenamide.

Figure 6.

Change from baseline in serum or plasma lipids at week 48. an = number of participants with nonmissing fasting lipid data at baseline and week 48, removing those with lipid-modifying agent administered at baseline (lipid data collected after initiation of a lipid-modifying agent were censored and a last observation carried forward method was applied so that the last available fasted, on-treatment lipid value before initiation of a lipid-modifying agent was used). bPercent change from baseline based on adjusted ratio (week 48 to baseline) in each group calculated from a repeated measures model applied to change from baseline in loge-transformed data adjusting for the following: treatment, visit, baseline third agent class, CD4+ cell count (continuous), loge-transformed baseline value (continuous), treatment-by-visit interaction, and baseline value-by-visit interaction, with visit as the repeated factor. *P = .017. **P < .001. Abbreviations: 3TC, lamivudine; DTG, dolutegravir; HDL, high-density lipoprotein; LDL, low-density lipoprotein; TAF, tenofovir alafenamide.