Phase III SWORD 1&2: Switch to DTG+RPV maintains virologic suppression at 48 weeks

Comment: Abstract follows:

This study demonstrates non-inferiority of treatment switch to dolutegravir/rilpivirine at 48 weeks versus remaining on current antiretroviral therapy. It’s satisfying to hear in person, data presented from a trial being conducted at our site.

Since 1996, triple therapy has been standard of care in treating HIV. As the HIV population ages, we are increasingly concerned by the potential toxicities associated with either TDF or abacavir use. While the development of TAF attempts to address this important clinical issue, it’s exciting that NRTI limiting strategies are also being pursued as an alternative strategy.

 Given its’ high genetic barrier to resistance, dolutegravir is an obvious candidate to explore this strategy and in addition to this study, late-breaker data regarding dolutegravir as maintenance monotherapy (Poster 451LB) will be presented in the coming days. A study of cabotegravir/rilpivirine as oral maintenance therapy is also being presented (Poster 442). 

44LB PHASE III SWORD 1&2: SWITCH TO DTG+RPV MAINTAINS VIROLOGIC SUPPRESSION THROUGH 48 WKS

Josep M. Llibre et al

Background: The requirement for life-long antiretroviral therapy (ART) of HIV infection has highlighted interest in 2-drug regimens (2DR) to minimize cumulative drug exposure. Dolutegravir’s (DTG) potency, safety and resistance barrier make it an optimal core agent for 2DR. Rilpivirine’s (RPV) safety, tolerability and efficacy in switch regimens make it an ideal potential partner.

Methods: Two identical open-label, multicenter, global, phase III, non-inferiority studies evaluated the efficacy and safety of switching from a 3 or 4-drug current antiretroviral regimen (CAR) to DTG+RPV once daily in HIV-1-infected adults, with HIV-1 RNA<50c/mL (VL<50c/mL) for at least 12 months and no history of virologic failure. Participants (pts) were randomized 1:1 (stratified by baseline 3rd agent class; age.

Results: 1024 pts were randomized and exposed (DTG+RPV 513; CAR 511), across both studies. Switching to DTG+RPV was non-inferior to continuing CAR at Wk48 for VL<50c/mL in pooled analysis of both the ITTe population [95% vs. 95%; difference: -0.4% (95% CI: -3.1%, 2.3%)] and the per-protocol population [96% vs. 96%; difference: 0.7% (95% CI: -3.3%, 1.8%)]. Efficacy results for SWORD-1 (VL<50c/mL in ITTe [95% vs. 96%; difference: -0.6% (95% CI: -4.3%, 3.0%)]) and SWORD-2 (VL<50c/mL in ITTe [94% vs. 95%;

difference: -0.2% (95% CI: -4.2%, 3.8%)]) were comparable. Low rates of snapshot virologic failures (VFs) at Wk48 were observed for both studies (Table 1). One pt on DTG+RPV with protocol defined VF had an NNRTI RAM (K101K/E); no pts had any INI RAMs. More adverse events (AEs) were reported and led to discontinuation in the DTG+RPV arm; no unexpected AEs were identified for either drug.

Conclusion: A switch to a novel, once daily 2DR of DTG+RPV demonstrated high efficacy and was non-inferior to the continuation of CAR in virologically suppressed HIV-1-infected adults. The safety profiles of both DTG and RPV were consistent with the respective labels. A DTG+RPV 2DR offers the potential for reduction in cumulative ART exposure, without an increased risk of virologic failure.