Glasgow 2018—Comparison of viral replication below 50 copies/mL for 2-drug (DTG + RPV) vs 3-drug current antiretroviral regimen (CAR) therapy in the SWORD-1 and SWORD-2 studies1
Author : Underwood M, Angelis K, Wang R, et al
Added On : 28/10/2018
Tags : Dolutegravir DTG rilpivirine RPV SWORD SWORD-1 SWORD-2 low-level viremia Abbot Realtime assay target detected target not detected
Introduction: Abbott Realtime assay measures quantitative HIV-1 RNA viral load (VL) from 40c/mL to 10,000,000c/mL, and generates qualitative target detected (TD) or target not detected (TND) for VL<40c/mL. FDA snapshot algorithm uses 50c/mL as cut-off. Clinical significance and subject management implications of low level quantitative and qualitative VL data remains controversial. We assessed the number of participants having 40c/mL≤VL<50c/mL and TD/TND over 48 weeks for DTG+RPV two-drug regimen versus CAR (PI-, NNRTI-, or INSTI-based three-drug current antiretroviral regimen).
Methodology: SWORD-1 and SWORD-2 are identical open-label, multicentre, global, phase III, non-inferiority studies evaluating efficacy and safety of switching from CAR to DTG+RPV once daily in HIV-1-infected adults, with HIV-1 RNA<50c/mL (VL<50c/mL) for at least 6 months and no history of virologic failure. We explored VL shifts from baseline, cumulative, and per visit classification of participants into >50 c/mL, 40c/mL≤VL<50c/mL, or TD/TND when <40c/mL, across arms throughout 48 Weeks.
Results: 1024 participants were randomized and exposed (DTG+RPV 513; CAR 511) across both studies. At Week 48, 95% of participants in both arms had Snapshot VL <50c/mL in Intention-To-Treat Exposed (ITT-E) population. Confirmed Virologic Withdrawal rates (CVW) were <1% in both arms. Similar proportion of participants at Week 48 had Snapshot VL <40c/mL and TND in the two arms (84% vs 80%, adjusted difference 3.1%, 95% CI -2.2%, 8.3%). Participants with Baseline TD had similar and low occurrence of at least one VL ≥50c/mL (DTG+RPV 14%; CAR 17%), or at least one VL between 40 c/mL and 50c/mL (DTG+RPV 4%; CAR 8%). Those participants with Baseline TND had similar and low occurrence of at least one VL≥50c/mL (DTG+RPV 5%; CAR 5%), or a similar percentage of at least one VL between 40c/mL and 50c/mL (DTG+RPV 3%, CAR 1%), or at least one VL<40c/mL and TD (DTG+RPV 44%; CAR 41%) through Week 48. See table 1.
Conclusions: DTG+RPV was non-inferior to CAR at Week 48 by Snapshot <50c/mL; The two groups were similar with Snapshot <40c/mL and TND as endpoint. Proportions of TD at Baseline and over time were similar between arms with higher rates of TD post-Baseline in those with TD at Baseline. Incident viremia (>40 and >50c/mL) was similar between arms by Baseline TD vs TND, but was more common with TD. However, this had limited clinical consequence, as efficacy rates were high (95%) and equal between arms and CVW numbers were low and equal between arms.
- Underwood M, Angelis K, Wang R, et al. Comparison of viral replication below 50 copies/mL for 2-drug (DTG + RPV) vs 3-drug current antiretroviral regimen (CAR) therapy in the SWORD-1 and SWORD-2 studies. Presented at: HIV Drug Therapy Glasgow 2018; October 28-31, 2018; Glasgow, UK.
UK/DTGP/0027/18 - November 2018