Trial Design

Two identically designed Phase 3, randomized, multicenter, open-label, parallel-group, noninferiority trials

Designed to evaluate the safety and efficacy of switching to JULUCA vs continuation of stable, suppressive ART (2 NRTIs plus either an INSTI, an NNRTI, or a PI)

Patients were treatment-experienced, virologically suppressed (HIV-1 RNA <50 copies/mL; on stable suppressive uninterrupted therapy for ≥6 months prior to screening) adults (≥18 years) with HIV-1

Exclusion criteria1

  • Severe hepatic impairment, positive for hepatitis B virus (HBV) surface antigen, or with an anticipated need for hepatitis C virus (HCV) therapy during the study
  • History of treatment failure
  • Known substitutions associated with resistance to dolutegravir or rilpivirine

 

ART=antiretroviral therapy; NRTIs=nucleoside reverse transcriptase inhibitors; INSTI=integrase strand transfer inhibitor; NNRTI=non-nucleoside reverse transcriptase inhibitor; PI=protease inhibitor.

SWORD 1 & 2: Baseline Characteristics and Study Design (pooled analysis)1

*70% of patients were on a baseline regimen of an FTC/TDF NRTI combination.

CDC=Centers for Disease Control and Prevention; FTC=emtricitabine; TDF=tenofovir disoproxil fumarate.

*At Week 48, patients in the continuing ART arm who remained virologically suppressed were switched to JULUCA at Week 52 and followed to Week 100.

For virologically suppressed adult patients with HIV-1

JULUCA Maintained Virologic Suppression as Effectively as Traditional 3-drug Regimens at 48 Weeks

 
  • Treatment difference was –0.2% (95% CI; –3.0%, 2.5%); assessed using a noninferiority margin of –8%1

 

Rates of virologic nonresponse

 

HIV-1 RNA ≥50 copies/mL: JULUCA <1% (n=3); continuing baseline ART 1% (n=6)

 

  • Treatment difference: –0.6% (95% CI; –1.7%, 0.6%); assessed using a noninferiority margin of –4%1

 

CI=confidence interval.

For virologically suppressed adult patients with HIV-1

Durable Virologic Suppression Maintained With JULUCA at Week 1002

 

Rates of virologic nonresponse at Week 100

  • HIV-1 RNA ≥50 copies/mL, 3% (n=13)2

For virologically suppressed adult patients with HIV-1

Patients Switched to JULUCA at Week 52 Maintained Virologic Suppression3

 

Rates of virologic nonresponse from Week 52 to Week 100

  • HIV-1 RNA ≥50 copies/mL, 2% (n=10)3

For virologically suppressed adult patients with HIV-1

High Barrier to Resistance Through Week 1002

  • One patient receiving JULUCA (dolutegravir and rilpivirine) had a detectable decrease in susceptibility (>4-fold) to the rilpivirine component of JULUCA in the resistance analysis data set (n=8 with confirmed HIV-1 RNA ≥200 copies/mL at failure or last visit and having resistance data)*

*The confirmed virologic failure population (pooled data from SWORD 1 & 2) who had 2 consecutive viral loads of ≥50 copies/mL, with the second one ≥200 copies/mL.
Resistance testing not performed in 2 patients (1 patient in each treatment arm) because of low viral load.
INSTI resistance test failed in 2 patients (1 patient in each treatment arm).

For virologically suppressed adult patients with HIV-1

Adverse Reactions and Rates of Discontinuation Due to Adverse Events Through Week 1002*

The most common adverse reactions Grades 1 to 4 with ≥2% frequency in the JULUCA arm through 48 weeks were diarrhea (2%) and headache (2%). Withdrawals due to adverse events through 48 weeks occurred in 4% (21/513) of patients in the JULUCA arm compared to <1% (3/511) with continuing ART.

 

 

*SWORD 1 & 2 (pooled data).
Most common AEs leading to discontinuation were psychiatric disorders: 2% of patients who continued on JULUCA through Week 100 and 1% of patients who switched to JULUCA at Week 52.
AEs=adverse events.

For virologically suppressed adult patients with HIV-1

Neutral Effect on Lipids

  • No discernible pattern of changes from baseline in mean serum concentrations of lipids at Week 1002

 

HDL=high-density lipoprotein; LDL=low-density lipoprotein.

For virologically suppressed adult patients with HIV-1

Fractures Reported in SWORD 1 & 2 (pooled data) at 48 Weeks

For virologically suppressed adult patients with HIV-1

A DEXA Substudy of SWORD 1 & 2 Evaluating Bone Mineral Density3

DEXA=dual-energy X-ray absorptiometry; BMD=bone mineral density.

  • BMD declines of ≥5% at the lumbar spine were experienced by 2% of patients receiving JULUCA and 5% of patients who continued their TDF-containing regimen
  • The long-term clinical significance of these BMD changes is not known

References:

  1. Llibre JM, Hung C-C, Brinson C, Castelli F, et al. Efficacy, safety, and tolerability of dolutegravir-rilpivirine for the maintenance of virological suppression in adults with HIV-1: phase 3, randomised, non-inferiority SWORD-1 and SWORD-2 studies. Lancet. 2018;391(10123):839-849.
  2. Aboud M, Orkin C, Podzamczer D, et al. Durable suppression 2 years after switch to the DTG+RPV 2-drug regimen: SWORD-1 and SWORD-2 studies. Presented at the 22nd International AIDS Conference (IAC); July 23-27, 2018; Amsterdam, the Netherlands. Poster THPEB047.
  3. Data on file, ViiV Healthcare.

Sword 1 and Sword 2 Trial Design