Glasgow 2018—Comparison of viral replication for 2-drug (DTG + RPV) vs 3-drug current antiretroviral regimen (CAR) in the SWORD-1 and SWORD-2 studies1

 

Introduction:  The overall goal of HIV therapy is to maintain virologic suppression over the entire course of a patient’s treatment. Despite that the clinical significance and subject management of transient ‘blips’ remains controversial, their appearance may lead to concerns about the durability of an ART regimen. Within the SWORD trial we assessed elevated viral loads, including blips during 2 years of study conduct with the 2-drug regimen (2DR) of DTG+RPV.

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) and no history of virologic failure. Subjects either switch to DTG+RPV on Day 1 (Early Switch (ES) DTG+RPV group) or remain on CAR (CAR group) and switch to DTG+RPV at Week 52 (Late Switch (LS) DTG+RPV group) if still on study and suppressed. FDA Snapshot algorithm uses HIV-1 RNA 50 copies/mL as the viral suppression cut-off. Patients with one or more on-treatment viral loads ≥50c/mL were categorized as either: (1) subjects with viral loads between 50-200 c/mL and no VL ≥200 c/mL and (2) subjects with at least one VL ≥200 c/mL. Blips were defined as any VL between 50 and 200 c/mL preceded and followed by VL below 50 c/mL.

Results: 1024 participants were randomized and exposed (DTG+RPV 513; CAR 511) across both studies. At Week100 in the ES DTG+RPV group, 456 (89%) participants had Snapshot VL <50c/mL and 6 (1.2%) met Confirmed Virologic Withdrawal (CVW) criterion, and in the LS DTG+RPV group, 444 (93%) had Snapshot VL <50c/mL and 2 (<1%) met CVW criterion. During the first year of exposure to DTG+RPV 34 (6.6%) and 20 (4.2%) participants had blips in the Early and Late Switch groups, respectively. During the second year of follow up of the ES DTG+RPV group there were only an additional 3% of subjects with blips.

Conclusions: The incidence of blips in the first year after switching to DTG+RPV 2DR was low in both the ES and LS DTG+RPV groups, and comparable to the 3-drug regimen comparator and remained low in the second year. All other categories of VL>50 occurred infrequently in all groups. These results suggest no difference in blip rates or any clinical consequences from VL elevations ≥200c/mL, as efficacy rates were high and equal between arms (95% each) and CVW numbers were low DTG+RPV and traditional 3 DRs of therapy.1

  1. Wang R, Underwood M, Koteff J, et al. Comparison of viral replication for 2-drug (DTG + RPV) vs 3-drug current antiretroviral regimen 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