after baseline correction were 10.7 (15.3) and 23.3 (28.4) ms, respectively. Steady-state administration of rilpivirine 75 mg once daily and 300 mg once daily resulted in a mean Cmax approximately 2.6-fold and 6.7-fold, respectively, higher than the mean steady-state Cmax observed with the recommended 25 mg once daily dose of rilpivirine (see section 4.4).
No relevant effects were seen with dolutegravir on the QTc interval, with doses exceeding the clinical dose by approximately three fold.
Clinical efficacy and safety
The efficacy and safety of switching from an antiretroviral regimen (containing 2 NRTIs plus either an INI, an NNRTI, or a PI) to a dual regimen of dolutegravir 50 mg and rilpivirine 25 mg was eva luated in 2 identical 48-week, randomised, open-label, multicentre, parallel-group, non-inferiority studies SWORD-1 (201636) and SWORD-2 (201637). Subjects were enrolled if they were on their first or second antiretroviral regimen with no history of virological failure, had no suspected or known resistance to any antiretroviral and had been stably suppressed (HIV-1 RNA < 50 copies/mL) for at least 6 months prior to screening. Subjects were randomised 1:1 to continue their CAR or be switched to a two-drug regimen dolutegravir plus rilpivirine administered once daily. The primary efficacy endpoint for the SWORD studies was the proportion of subjects with plasma HIV-1 RNA <50 copies/mL at Week 48 (Snapshot algorithm for the ITT-E population).
At baseline, in the pooled analysis, characteristics were similar between treatment arms with the median age of subjects of 43 years (28%, 50 years of age or older; 3%, 65 years of age or older), 22% female, 20% non-white and 77% were CDC Class A. Median CD+cell count was about 600 cells per mm3 with 11% having CD4+ cell count less than 350 cells per mm3. In the pooled analysis, 54%, 26%, and 20% of subjects were receiving an NNRTI, PI, or INI (respectively) as their baseline third treatment agent class prior to randomisation.
The pooled primary analysis demonstrated that dolutegravir plus rilpivirine is non-inferior to CAR, with 95% of subjects in both arms achieving the primary endpoint of <50 copies/mL plasma HIV-1 RNA at Week 48 based on the Snapshot algorithm (Table 3).
The primary endpoint and other outcomes (including outcomes by key baseline covariates) for the pooled SWORD-1 and SWORD-2 studies are shown in Table 3.
Table 3: Virologic Outcomes of Randomized Treatment at Week 48 (Snapshot algorithm)
SWORD-1 and SWORD-2 Pooled Data***
DTG + RPV
N=513
n (%)
CAR
N=511
n (%)
HIV-1 RNA <50 copies/mL
486 (95%)
485 (95%)
Treatment Difference*
-0.2 (-3.0, 2.5)
Virologic non response**
3 (<1%)
6 (1%)
Reasons
Data in window not <50 copies/mL
0
2 (<1%)
Discontinued for lack of efficacy
2 (<1%)
2 (<1%)
Discontinued for other reasons while not <50 copies/mL
1 (<1%)
1 (<1%)
Change in ART
0
1 (<1%)
No virologic data at Week 48 window
24 (5%)
20 (4%)
Reasons
Discontinued study/study drug due to adverse event or death
17 (3%)
3 (<1%)
Discontinued study/study drug for other reasons
7 (1%)
16 (3%)
Missing data during window but on study
0
1 (<1%)
HIV-1 RNA <50 copies/mL by baseline covariates
n/N (%)
n/N (%)
Baseline CD4+ (cells/ mm3)
<350
51 / 58 (88%)
46 / 52 (88%)
≥350
435 / 455 (96%)
439 / 459 (96%)
Baseline Third Treatment Agent Class
INI
99 / 105 (94%)
92 / 97 (95%)
NNRTI
263 / 275 |
