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.

Background Switching to dolutegravir/lamivudine (DTG/3TC) was non-inferior to continuing tenofovir alafenamide (TAF)-based regimens for maintaining virologic suppression at Week 48 of the TANGO study. Here we present Week 144 outcomes (efficacy, safety, weight, and biomarkers). Methods TANGO is a randomized (1:1, stratified by baseline third agent class), open-label, non-inferiority phase 3 study. Virologically suppressed (>6 months) adults with HIV-1 switched to once-daily DTG/3TC or continued TAF-based regimens. Results 741 participants received study treatment (DTG/3TC, n=369; TAF-based regimen, n=372). At Week 144, proportion of participants with HIV-1 RNA ≥50 copies/mL (primary endpoint, Snapshot, intention-to-treat–exposed population) after switching to DTG/3TC was 0.3% (1/369) vs 1.3% (5/372) of those continuing TAF-based regimens, demonstrating non-inferiority (adjusted treatment difference, −1.1; 95% CI, −2.4, 0.2), and favored DTG/3TC in the per-protocol analysis (adjusted treatment difference, −1.1; 95% CI, −2.3, −0.0; P=0.044). Few participants met confirmed virologic withdrawal criteria (DTG/3TC, n=0; TAF-based regimen, n=3), with no resistance observed. Drug-related adverse events were more frequent with DTG/3TC (15%; 4% led to discontinuation) than TAF-based regimens (5%; 1% led to discontinuation) through Week 144 and were comparable post-Week 48 (4%; 1% led to discontinuation in both groups). Change from baseline in lipids generally favored DTG/3TC; no clinical impact on renal function and comparable changes in inflammatory and bone biomarkers across groups were observed. Conclusions Switching to DTG/3TC demonstrated non-inferior and durable efficacy vs continuing TAF-based regimens in treatment-experienced adults with HIV-1, with good safety and tolerability, and no resistance through 144 weeks

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As treatment improves, people living with HIV (PLWHIV) can now expect to live longer, which means that the foci of HIV-related care for them and their medical practitioners continue to change. With an increasingly older cohort of patients with HIV infection, practitioners' key considerations are shifting from issues of acute treatment and patient survival to multiple comorbidities, toxicities associated with chronic therapy, and ongoing health maintenance. Within this context, this paper explores the current standard of practice for the management of HIV infection in Australia. We surveyed 56 Australian practitioners currently involved in managing HIV infection: 'HIV section 100' (HIV therapy-prescribing) general practitioners (s100 GPs; n = 26), sexual health physicians (SHPs; n = 24) and hospital-based physicians (HBPs; n = 6). Survey results for practice approaches and challenges were broadly consistent across the three practitioner specialties, apart from a few key areas. s100 GPs reported less prophylaxis use among patients whom they deemed at risk of HIV infection in comparison with SHPs, which may reflect differences in patient populations. Further, a higher proportion of s100 GPs nominated older HIV treatment regimens as their preferred therapy choices compared with the other specialties. In contrast with SHPs, s100 GPs were less likely to switch HIV therapies to simplify the treatment protocol, and to immediately initiate treatment upon patient request in those newly diagnosed with HIV infection. Considerably lower levels of satisfaction with current HIV practice guidelines were also reported by s100 GPs. It appears that greater support for s100 GPs may be needed to address these identified challenges and enhance approaches to HIV practice. Across all specialties, increasing access to mental health services for patients with HIV infection was reported as a key management issue. A renewed focus on providing improved mental health and wellbeing supports is recommended, particularly in the face of an ageing HIV-infected population.

Background DTG/3TC is a complete 2-drug regimen (2DR) for the treatment of HIV-1 infection. Non-inferior virologic efficacy has been proven over 3 years in treatment-naive people living with HIV (PLWH) and 2 years in a stable switch setting. Methods TANGO, a randomized, open-label, non-inferiority study, evaluates efficacy and safety of switching to DTG/3TC in PLWH who are virologically suppressed ( > 6 months, no prior virologic failure [VF], no major NRTI/INSTI resistance) vs remaining on a 3- or 4-drug TAF-based regimen (TBR), stratified by baseline 3rd agent class. Week 144 analyses assessed non-inferiority (NI) with a 4% NI margin for Snapshot virologic failure (VF) and 8% for virologic success (VS; FDA Snapshot algorithm, intention-to-treat–exposed [ITT-E] population). Results Of 741 randomized/exposed pts (DTG/3TC: 369; TBR: 372), most pts entered the study on EVG/c (66%). For Week 144 Snapshot VF, switching to DTG/3TC was non-inferior to continuing TBR in the ITT-E analysis: 0.3% vs 1.3%; adjusted difference (95% CI): −1.1% (−2.4%, 0.2%) and superior to TBR in the per-protocol analysis: 0% vs 1.1%; adjusted difference: −1.1% (−2.3, −0.0); P=0.044 (2-sided). Snapshot VS was high in both arms and demonstrated non-inferiority (Table). Zero pts on DTG/3TC and 3 (0.8%) on TBR met confirmed virologic withdrawal criteria with no resistance observed. Zero pts on DTG/3TC and 6 (1.6%) on TBR discontinued for lack of efficacy. Overall AE rates were similar between arms (Table). TC, LDL-C, and triglycerides improved with DTG/3TC, HDL-C improved with TBR, with no difference in TC/HDL-C ratio between arms. Changes in eGFR (cystatin C) and proximal tubular function marker were similar across arms. Adjusted mean change from BL in weight was 2.2 and 1.7 kg in the DTG/3TC and TBR arms, respectively, and proportion of pts with > 10% weight increase was similar across arms (13% and 12%, respectively). Table. Efficacy and Key Safety Results for the ITT-E and Safety Population Conclusion Switching to the 2-drug regimen of DTG/3TC from a TAF-based 3- or 4-drug regimen resulted in high, non-inferior efficacy with zero confirmed virologic withdrawals and good tolerability over 3 years of treatment. DTG/3TC 2DR is a robust switch option with durable efficacy, good safety and tolerability, and a high barrier to resistance. Disclosures Olayemi Osiyemi, M.D, Gilead (Advisor or Review Panel member, Speaker’s Bureau)Merck (Advisor or Review Panel member)ViiV Healthcare (Advisor or Review Panel member, Speaker’s Bureau) Fiona Bisshop, MBBBS, Gilead (Grant/Research Support)ViiV Healthcare (Grant/Research Support) Stéphane De Wit, MD, Gilead (Grant/Research Support)Janssen (Grant/Research Support)Merck Sharpe & Dohme (Grant/Research Support)ViiV Healthcare (Grant/Research Support) Joaquín Portilla, MD, AbbVie (Other Financial or Material Support)Gilead (Grant/Research Support, Other Financial or Material Support)Janssen (Grant/Research Support, Other Financial or Material Support)Merck Sharpe & Dohme (Other Financial or Material Support)ViiV Healthcare (Grant/Research Support, Other Financial or Material Support) Jean-Pierre Routy, MD, FRCPC, ViiV Healthcare (Grant/Research Support) Mounir Ait-Khaled, PhD, ViiV Healthcare (Employee) Keith Pappa, PharmD, Glaxo Smith Kline (Shareholder)ViiV Healthcare (Employee) Ruolan Wang, Master of Science, ViiV Healthcare (Employee) Peter Leone, MD, viiv healthcare (Employee) Jonathan Wright, MSc, GlaxoSmithKline (Employee, Shareholder) Brian Wynne, MD, ViiV Healthcare (Employee, Shareholder, I have shares in GSK, the part owner of ViiV) Jean A. van Wyk, MB,ChB, GlaxoSmithKline (Shareholder)ViiV Healthcare (Employee) Michael Aboud, MBChB, MRCP, GlaxoSmithKline (Shareholder)ViiV Healthcare (Employee) Kimberly Smith, MD, GlaxoSmithKline (Shareholder)ViiV Healthcare (Employee)