1. Switch to DTG + RPV Switch to DTG + RPV SWORD Study
ARV-trial.com
Switch to DTG + RPV
Switch to DTG + RPV
SWORD Study
Switch to CAB LA + RPV LA IM
LATTE-2 Study

2. SWORD-1 & 2 Studies: Switch to DTG + RPV
ARV-trial.com
SWORD-1 & 2 Studies: Switch to DTG + RPV
Design
Randomisation
1:1
Open-label
W48
W148
HIV+ ≥ 18 years
On stable cART ≥ 6 months
(2 NRTI + INSTI or PI/r or NNRTI)
1st or 2nd cART with no prior
change for virologic failure
HIV RNA < 50 c/mL ≥ 12 months
HBs Ag negative
N = 513
DTG 50 mg QD + RPV 25 mg QD
DTG 50 mg QD + RPV 25 mg QD
Continuation
of cART
N = 511
Endpoint
Primary: proportion of patients maintaining HIV RNA < 50 c/mL at W48 (ITT-exposed, snapshot) ; non-inferiority if lower margin of a two-sided 95% CI for the difference = - 8% for pooled studies (- 10% for each individual study)
SWORD
Llibre JM. Lancet. 2018;391:839-49

3. SWORD-1 & 2 Studies: Switch to DTG + RPV
ARV-trial.com
SWORD-1 & 2 Studies: Switch to DTG + RPV
Baseline characteristics and patient disposition
DTG + RPV
N = 513
Continuation cART
N = 511
Mean age, years 43
Female, % 23 21
Race: non white, % 18 22
CD4/mm3, median
611
638
Baseline cART, %
PI-based
NNRTI-based
INSTI-based
With TDF
Duration of cART prior to Day 1, median months 51 53
Discontinuation by W52, N (%)
Adverse event
Lack of efficacy
Investigator decision
Consent withdrawal
Lost to follow-up
Protocol deviation
Protocol-defined stopping criteria
29 (5.7%) 17 3 5 2 1
34 (6.7%) 14 7
SWORD
Llibre JM. Lancet. 2018;391:839-49

4. SWORD-1 & 2 Studies: Switch to DTG + RPV
ARV-trial.com
SWORD-1 & 2 Studies: Switch to DTG + RPV
Virologic outcome at W48 (ITT-E, snapshot)
Other virologic results
at W48
Difference (95% CI) = - 0.2% (- 3.0 to 2.5)
94.7
0.6
4.7
94.9
1.2
3.9 20 40 60 80
100
Success
HIV RNA < 50 c/mL
Virologic
non-response
No virologic data %
DTG + RPV
Continuation cART
HIV RNA < 50 c/mL (ITT-E snapshot)
SWORD-1
95% DTG + RPV
96% continuation cART
Adjusted ≠: - 0.6% (95% CI: to + 3.0)
SWORD-2
94% DTG + RPV
94% continuation cART
Adjusted ≠: 0.2% (95% CI: to + 4.2)
Confirmed virologic failure: HIV RNA ≥ 50 c/mL, retest ≥ 200 c/mL
DTG + RPV, N = 2
Emergence of NNRTI resistance mutation (K101K/E)
Continued cART, N = 2
No mutations
SWORD
Llibre JM. Lancet. 2018;391:839-49

5. SWORD-1 & 2 Studies: Switch to DTG + RPV
ARV-trial.com
SWORD-1 & 2 Studies: Switch to DTG + RPV 80
HIV RNA of subject with NNRTI-resistant mutation
41-year-old female
Pre-cART HIV RNA > 2 millions c/mL ; 1st cART: TDF/FTC/EFV
Randomised to DTG + RPV
Documented non-adherence before W36 D1 W8 W4
W12
W36
W24
W39
W45
Screening
K101K/E on genotype
(fold change RPV = 1.2) ;
phenotype: sensitive to RPV
Resuppressed
on DTG + RPV
HIV RNA, c/mL
SWORD
Llibre JM. Lancet. 2018;391:839-49

6. SWORD-1 & 2 Studies: Switch to DTG + RPV
ARV-trial.com
SWORD-1 & 2 Studies: Switch to DTG + RPV
Adverse events at W48, %
DTG + RPV
N = 513
Continued cART
N = 511
Adverse events related to study drug
Grade 1-2
Grade 3-4 17 2
< 1
Serious adverse event 5 4
Adverse event leading to discontinuation
CNS adverse event leading to withdrawal
4.1 (N = 21 *)
N = 9
0.6 (N = 3)
N = 1
Most common adverse events (≥ 5% of patients)
Nasopharyngitis
Headache
Upper respiratory tract infection
Diarrhea
Back pain
10 8 6 3
10 5 7
* (some participants have more than 1 AE) ; anxiety (N = 4), depression (N = 3), insomnia (N = 2), depressed mood (N = 1), headache (N = 1), panic attack (N = 1), suicidal ideation (N = 1), tremor (N = 1), drug-induced liver injury (N = 1), eosinophilic pneumonia, acute (N = 1), abdominal distension (N = 2), dyspepsia (N = 2), peptic ulcer (N = 1), gastrointestinal haemorrhage (N = 1), pancreatitis, acute (N = 1), Hodgkin’s disease (N = 1), Kaposi sarcoma (N = 1), plasmablastic lymphoma (N = 1)
SWORD
Llibre JM. Lancet. 2018;391:839-49

7. SWORD-1 & 2 Studies: Switch to DTG + RPV
ARV-trial.com
SWORD-1 & 2 Studies: Switch to DTG + RPV
Fasting lipids at baseline and W48
Baseline
DTG + RPV
Continuation cART
mg/dL
Total cholesterol
HDL cholesterol
LDL cholesterol, calculated
Triglycerides
185.9 50
100
150
200
186
187.6
188.1
52.7
54.2
53.6
54.9
107.1
108.1
108.3
107.3
133.1
121.3
132.0
W48
Total cholesterol: HDL ratio 5 4 3 2 1
3.8
3.7
SWORD
Llibre JM. Lancet. 2018;391:839-49

8. SWORD-1 & 2 Studies: Switch to DTG + RPV
ARV-trial.com
SWORD-1 & 2 Studies: Switch to DTG + RPV
Conclusion at W48
A switch to a novel, once-daily 2 drug-regimen of DTG + RPV demonstrated high efficacy and was non-inferior to the continuation of a combined antiretroviral therapy in virologically suppressed HIV-1–infected adults
The safety profiles of both DTG and RPV were consistent with their respective labels
Switching to DTG + RPV had a neutral effect on lipids, while significantly improving bone turnover biomarkers 
SWORD
Llibre JM. Lancet. 2018;391:839-49

9. SWORD-1 & 2 Studies: Switch to DTG + RPV (W100 results)90
HIV RNA < 50 c/mL at W100, ITT snapshot 95 20 40 60 80
100
DO-W48
DTG + RPV
(N = 513)
Continuation cART
(N = 511) %
D0-W100
Deferred Switch
DTG + RPV W52-W100
(N = 477) 89 93
Confirmed virologic failure: 2 consecutive HIV RNA ≥ 50 c/mL, with HIV RNA ≥ 200 c/mL on confirmation sample
10/990 (1 %) patients on DTG + RPV between D0 and W100
No emergence of resistance mutation to INSTI
Emergence of resistance mutation to NNRTI: 3/10
SWORD
Aboud M, IAC 2018, Abs. THPEB047

10. SWORD-1 & 2 Studies: Switch to DTG + RPV (W100 results)91
Virologic failure on DTG + RPV between D0 and W100, N = 10 *
Failure
Previous ARV regimen
HIV RNA, c/mL
Resistance mutations
Fold Change
DNA genotype at baseline
Plasma genotype at failure
NNRTI
INSTI
INNTI
W24
EFV/TDF/FTC
88 ; 466
G193E
DTG : 1.02
W36
1059 ; 771
K101K/E
RPV : 1.21
W64
DTG/ABC/3TC
833
N155N/H, G163G/R ?
Amplification
failure ND
W76
ATV/ABC/3TC 79 -
W88
278
E138E/A
RPV : 1.61
DTG : 0.72
RPV/TDF/FTC
147 NR
W100
651
K101E, E138A
K101E, E138A, M230M/L
RPV : 31
DTG : ND
ATV/r/TDF/FTC
280
* Results available for 8/10 patients
In red: emerging mutations
SWORD
Aboud M, IAC 2018, Abs. THPEB047

11. SWORD-1 & 2 Studies: Switch to DTG + RPV (W100 results)90
Cumulative adverse events, %
DTG + RPV
N = 513
D0-W100
Deferred DTG + RPV
N = 477
W52-W100
Adverse events related to study drug 20 12
Drug-related adverse events in ≥ 2%
Headache
Nausea 2 1
Serious adverse event 11 6
Adverse event leading to discontinuation
Psychiatric disorders
7 (N = 34 *)
2.3
3 (N = 15 *)
1.0
Adverse events leading to DTG + RPV discontinuation: 49/990 (5%) at W100 including 17 for psychiatric disorders: suicidal ideation (N = 5), suicide (N = 1), anxiety (N = 4), depression (N = 5), depressed mood (N = 1), insomnia (N = 5), nightmare (N = 1), affective disorder (N = 1), abulia (N = 1), confusional state (N = 1), loss of libido (N = 1)
Bone, atherogenesis and inflammation biomarkers: no change on DTG + 3TC between W48 and W100
Renal tubular proteinuria (RBP/creatininuria and b2M/creatininuria): improvement maintained in immediate switch group at W100
SWORD
Aboud M, IAC 2018, Abs. THPEB047