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Phase 3 Completed N=508 Randomized Treatment

Regimen Switch to Dolutegravir + Rilpivirine From Current Antiretroviral Regimen in Human Immunodeficiency Virus Type 1 Infected and Virologically Suppressed Adults (SWORD-1)

Source: ClinicalTrials.gov NCT02429791 ↗
Enrolled (actual)
508
Serious AEs
6.9%
Results posted
Dec 2017
Primary outcomePrimary: Percentage of Participants With Plasma HIV-1 RNA <50 c/mL at Week 48 Using Snapshot Algorithm — 95; 96 Percentage of participants
◆ Published Evidence
Highly cited
359citations · ~45 / year
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 (London, England) · 2018 · Likely link

Summary

The aim of this study was to determine if virologically suppressed human immunodeficiency virus type 1 (HIV-1) infected adults on an antiretroviral regimen (including 2 nucleoside reverse transcriptase inhibitors [NRTIs] plus a third agent) remain suppressed upon switching to a two-drug regimen with dolutegravir (DTG) + rilpivirine (RPV). The study primarily assessed the non-inferiority antiviral activity of switching to DTG + RPV once daily compared to continuation of current antiretroviral regimen (CAR) up to Week 48 with a switch visit for eligible subjects in the CAR group to initiate DTG + RPV therapy at Week 52. CAR included 2 NRTIs plus 1 HIV-1 integrase inhibitor (INI), or 1 non-nucleoside reverse transcriptase inhibitor (NNRTI), or 1 protease inhibitor (PI). The study included a 148-week open-label treatment phase, comprising of an Early Switch Phase (Day 1 to Week 52) and a Late Switch Phase (Week 52 to Week 148). The participants fulfilling the study eligibility criteria participated in the Early Switch Phase where they either switched from their CAR to DTG + RPV, or continued taking their CAR, until Week 52. At the end of Early Switch Phase, eligible participants proceeded to the Late Switch Phase where all participants in both DTG + RPV and CAR treatment groups received DTG + RPV therapy until Week 148. After Week 148, eligible subjects were given the opportunity to continue receiving DTG +RPV, in the Continuation Phase.

Linked Publications (3)

  • 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 (London, England) · 2018 · 359 citations · Likely link
  • Efficacy and safety of dolutegravir-rilpivirine for maintenance of virological suppression in adults with HIV-1: 100-week data from the randomised, open-label, phase 3 SWORD-1 and SWORD-2 studies.
    The lancet. HIV · 2019 · 122 citations · Likely link
  • Switch from tenofovir disoproxil fumarate combination to dolutegravir with rilpivirine improves parameters of bone health.
    AIDS (London, England) · 2018 · 55 citations · Open access · Likely link

Outcome Measures

OutcomeResultp-value
PRIMARY
Percentage of Participants With Plasma HIV-1 RNA <50 c/mL at Week 48 Using Snapshot Algorithm
95; 96 —
SECONDARY
Changes From Baseline in Cluster Designation (CD)4+ Lymphocyte Count at Weeks 24 and 48
16.2; 47.4; 32.3; 41.8 —
SECONDARY
Percentage of Participants With Plasma HIV 1 RNA <50 c/mL at Week 24 Using Snapshot Algorithm
98; 96 —
SECONDARY
Number of Participants With Common Non-serious Adverse Event (AE), Any Serious AE (SAE), AE of Maximum Toxicity Grade 1, 2, 3 or 4 and AE Leading to Discontinuation (AELD)
158; 126; 37; 30; 82; 73 —
SECONDARY
Number of Participants With Maximum Post-baseline Emergent Chemistry Toxicities Over 48 Weeks
95; 78; 61; 86; 22; 23 —
SECONDARY
Number of Participants With Maximum Post-Baseline Emergent Hematology Toxicities Over 48 Weeks
11; 11; 3; 2; 3; 1 —
SECONDARY
Mean Change From Baseline in High-sensitivity C-reactive Protein (Hs-CRP) at Week 48
0.11; 0.15 —
SECONDARY
Mean Change From Baseline in Cystatin C at Week 48
0.00; -0.01 —
SECONDARY
Mean Change From Baseline in D-Dimer at Week 48
-0.02; 0.02 —
SECONDARY
Mean Change From Baseline in Fatty Acid Binding Protein 2 (FABP) and Soluble Cluster Designation (CD)14 at Week 48
-2.79; -1.93; 379.72; 754.54 —
SECONDARY
Mean Change From Baseline in Soluble CD163 and Oxidized Low Density Lipoprotein (LDL) at Week 48
50.18; 54.26; 9.49; -41.30 —
SECONDARY
Mean Change From Baseline in Retinol Binding Protein (RBP), Serum Creatinine and Glucose at Week 48
-0.13; 0.03; 0.087; 0.011; 0.762; 2.492 —
SECONDARY
Mean Change From Baseline in Urine Phosphate at Week 48
-1.079; -1.511 —
SECONDARY
Mean Change From Baseline in Beta-2-microglobulin (B2M) (Blood and Urine), Urine RBP and 25 Hydroxy-vitamin D (Blood) at Week 48
-15.1452; -4.5995; -13.9; -8.2; -128.2045; 39.8394 0.007 sig
SECONDARY
Mean Change From Baseline in Urine Albumin/Creatinine Ratio and Urine Protein/Creatinine Ratio at Week 48
-1.19; -2.59; -5.63; -1.43 —
SECONDARY
Mean Change From Baseline in Bone-specific Alkaline Phosphatase, Procollagen 1 N-terminal Propeptide, Osteocalcin, Type I Collagen C-Telopeptides and Soluble Vascular Cell Adhesion Molecule (sVCAM) at Week 48
-2.89; 0.90; -9.1; -1.4; -4.40; -0.68 0.001 sig
SECONDARY
Mean Change From Baseline in Interleukin 6 (IL-6) at Week 48
0.17; -0.18 —
SECONDARY
Mean Change From Baseline in Insulin Resistance Based on Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) at Week 48
-0.30; 0.51 —
SECONDARY
Mean Change From Baseline in Fasting Lipids at Weeks 24 and 48
0.076; 0.061; 0.089; 0.064; 0.165; 0.103 —
SECONDARY
Number of Participants With Genotypic Resistance- Early Switch Phase
1; NA; 0; NA; 0; NA —
SECONDARY
Number of Participants With Genotypic Resistance-DTG+RPV Group Through Early and Late Switch Phase
5; 0; 0; 0; 0; 4 —
SECONDARY
Number of Participants With Genotypic Resistance-CAR Group Through Late Switch Phase
1; 0; 0; 0; 0; 1 —
SECONDARY
Number of Participants With Phenotypic Resistance-Early Switch Phase
0; 0; 0; 0; 1; 1 —
SECONDARY
Number of Participants With Phenotypic Resistance-DTG+RPV Group Through Early and Late Switch Phase
0; 0; 5; 0; 0; 5 —
SECONDARY
Number of Participants With Phenotypic Resistance-CAR Group Through Late Switch Phase
1; 0; 0; 1; 0; 0 —
SECONDARY
Pre-dose Concentrations of DTG and RPV at Weeks 4, 24, 48, 56, 76 and 100 in Participants Switching to DTG + RPV-DTG+RPV Group Through Early and Late Switch Phase
1581.06; 92.05; 1835.68; 87.88; 1915.11; 95.18 —
SECONDARY
Pre-dose Concentrations of DTG and RPV at Weeks 56, 76 and 100 in Participants Switching to DTG+RPV-CAR Group Through Late Switch Phase
1738.55; 84.14; 1800.39; 97.79; 1907.20; 101.93 —
SECONDARY
Pre-dose Concentrations of DTG and RPV at Weeks 2, 4 and 8 in the First 20 Participants Who Switch From Efavirenz (EFV) or Nevirapine (NVP) to DTG + RPV
821.25; 65.360; 994.00; 67.374; 1561.34; 77.416 —
SECONDARY
Percentage of Participants With Plasma HIV 1 RNA <50 c/mL at Week 48 Using Snapshot Algorithm by Baseline Third Agent Treatment Class
95; 98; 98; 96; 95; 92 0.317
SECONDARY
Changes From Baseline in Cluster Designation (CD)4+ Lymphocyte Count at Week 48 by Baseline Third Agent Treatment Class
47.9; 25.0; 19.9; 39.9; 12.5; 74.7 —
SECONDARY
Number of Participants With Any AE, AELD or AE With Grade 1, 2, 3 or 4 Toxicity Over 48 Weeks by Baseline Third Agent Treatment Class
102; 98; 38; 34; 60; 58 —
SECONDARY
Number of Participants With Maximum Post-baseline Emergent Chemistry Toxicities Over 48 Weeks by Baseline Third Agent Treatment Class
47; 42; 32; 48; 13; 13 —
SECONDARY
Number of Participants With Maximum Post-Baseline Emergent Hematology Toxicities Over 48 Weeks by Baseline Third Agent Treatment Class
5; 3; 1; 1; 1; 1 —
SECONDARY
Number of Participants With Observed Genotypic Resistance for Participants Meeting Virologic Withdrawal Criteria by Baseline Third Agent Treatment Class
— —
SECONDARY
Number of Participants With Observed Phenotypic Resistance for Participants Meeting Virologic Withdrawal Criteria by Baseline Third Agent Treatment Class
— —
SECONDARY
Change From Baseline in Fasting Lipids at Weeks 24 and 48 by Baseline Third Agent Treatment Class
3.239; 2.375; 3.596; 2.472; 3.383; 4.099 —
SECONDARY
Change From Baseline in Pre-specified Treatment Symptoms Using the Symptom Distress Module at Weeks 4, 24 and 48-Early Switch Phase
-1.6; 0.2; -0.8; -0.2; -0.4; 0.0 0.940
SECONDARY
Change From Baseline in Pre-specified Treatment Symptoms Using the Symptom Distress Module at Weeks 56, 76, 100 and 148-DTG+RPV Group Through Early and Late Switch Phase
-0.9; -0.2; -0.4; -0.6; -1.6; -0.9 —
SECONDARY
Change From LS Baseline in Pre-specified Treatment Symptoms Using the Symptom Distress Module at Weeks 56, 76, 100 and 148-CAR Group Through Late Switch Phase
-0.7; 0.1; 0.0; 0.4; -2.0; -0.4 —
SECONDARY
Change From Baseline Treatment Satisfaction Using the HIV Treatment Satisfaction Questionnaire (HIV TSQ) at Weeks 4, 24 and 48-Early Switch Phase
0.0; 0.0; 1.0; 0.0; 0.5; 0.0 0.002 sig
SECONDARY
Change From Baseline Treatment Satisfaction Using HIV TSQ at Weeks 56, 76, 100 and 148 - DTG+RPV Group Through Early and Late Switch Phase
0.0; 0.5; 0.0; 1.0; 0.0; 0.0 —
SECONDARY
Change From LS Baseline Treatment Satisfaction Using HIV TSQ at Weeks 56, 76, 100 and 148-CAR Group Through Late Switch Phase
0.0; 0.0; 0.0; 0.0; 0.0; 0.0 —
SECONDARY
Number of Participants With Observed Genotypic Resistance for Participants Meeting Virologic Withdrawal Criteria by Baseline Third Agent Treatment Class-DTG+RPV Group Through Continuation Phase
3; 0; 0; 0; 0; 3 —
SECONDARY
Number of Participants With Observed Phenotypic Resistance for Participants Meeting Virologic Withdrawal Criteria by Baseline Third Agent Treatment Class-DTG+RPV Group Through Continuation Phase
0; 0; 2; 0; 0; 2 —
SECONDARY
Number of Participants With Observed Genotypic Resistance for Participants Meeting Virologic Withdrawal Criteria by Baseline Third Agent Treatment Class- CAR Group Through Continuation Phase
1; 0; 0; 0; 0; 1 —
SECONDARY
Number of Participants With Observed Phenotypic Resistance for Participants Meeting Virologic Withdrawal Criteria by Baseline Third Agent Treatment Class- CAR Group Through Continuation Phase
1; 0; 0; 1; 0; 0 —
SECONDARY
Number of Participants With Genotypic Resistance-DTG+RPV Group Through Continuation Phase
6; 0; 0; 0; 0; 5 —
SECONDARY
Number of Participants With Phenotypic Resistance-DTG+RPV Group Through Continuation Phase
0; 0; 5; 0; 0; 5 —
SECONDARY
Number of Participants With Genotypic Resistance-CAR Group Through Continuation Phase
1; 0; 0; 0; 0; 1 —
SECONDARY
Number of Participants With Phenotypic Resistance- CAR Group Through Continuation Phase
1; 0; 0; 1; 0; 0 —

Eligibility Criteria

Inclusion Criteria

  • Participants must have been able to understand and comply with protocol requirements, instructions, and restrictions.
  • Participants must have been likely to complete the study as planned.
  • Participants must have been considered appropriate candidates for participation in an investigative clinical trial with oral medication (e.g., no active substance abuse, acute major organ disease, or planned long-term work assignments out of the country, etc.).
  • HIV-1 infected men or women of greater than or equal to (>=)18 years of age.
  • Must have been on uninterrupted current regimen (either the initial or second combination antiretroviral therapy [cART] regimen) for at least 6 months prior to screening; Any prior switch, defined as a change of a single drug or multiple drugs simultaneously, must have occurred due to tolerability and/or safety concerns or access to medications, or convenience/simplification. Acceptable stable cART regimens prior to screening include 2 NRTIs plus INI (either the initial or second cART regimen), or an NNRTI (either the initial or second cART regimen), or a Boosted PI (or atazanavir unboosted) (either the initial or second PI-based cART regimen).
  • Documented evidence of at least two plasma HIV-1 RNA measurements =45 years of age) or physically incapable of becoming pregnant with documented tubal ligation, hysterectomy or bilateral oophorectomy or, Child-bearing potential with a negative pregnancy test at both Screening and Day 1 and agrees to use one of the following methods of contraception to avoid pregnancy: Complete abstinence from intercourse from 2 weeks prior to administration of study drug, throughout the study, and for at least 2 weeks after discontinuation of all study medications and completion of the Follow-up visit; Any intrauterine device (IUD) with published data showing that the expected failure rate is =50 c/mL.
  • Within the 6 to 12 month window prior to screening and after confirmed suppression to 200 c/mL.
  • Within the 6 to 12 month window prior to screening and after confirmed suppression to =50 c/mL.
  • Any drug holiday during the window between initiating first HIV ART and 6 months prior to screening, except for brief periods (less than 1 month) where all ART was stopped due to tolerability and/or safety concerns.
  • Any switch to a second line regimen, defined as change of a single drug or multiple drugs simultaneously, due to virologic failure to therapy (defined as a confirmed plasma HIV 1 RNA measurement >=400 c/mL after initial suppression to =5 × upper limit of normal (ULN), or ALT >=3 × ULN and bilirubin >=1.5 × ULN (with greater than [>] 35% direct bilirubin).
  • Corrected QT interval (QTc [Bazett]) >450 milliseconds or QTc (Bazett) >480 milliseconds for participants with bundle branch block. The QTc was the QT interval corrected for heart rate according to Bazett's formula (QTcB).
View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT02429791) and the linked publication. Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.

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