(96%)
265 / 278 (95%)
PI
124 / 133 (93%)
128 / 136 (94%)
Gender
Male
375 / 393 (95%)
387 / 403 (96%)
Female
111 / 120 (93%)
98 / 108 (91%)
Race
White
395 / 421 (94%)
380 / 400 (95%)
African-America/African Heritage/Other
91 / 92 (99%)
105 / 111 (95%)
Age (years)
<50
350 / 366 (96%)
348 / 369 (94%)
≥50
136 / 147 (93%)
137 / 142 (96%)
* Adjusted for baseline stratification factors and assessed using a non-inferiority margin of - 8%.
** Non-inferiority of dolutegravir plus rilpivirine to CAR, in the proportion of subjects classified as virologic non-responders, was demonstrated using a non-inferiority margin of 4%. Adjusted difference (95% CI) -0.6 (-1.7, 0.6).
*** The results of the pooled analysis are in line with those of the individual studies, for which differences in proportions meeting the primary endpoint of <50 copies/mL plasma HIV-1 RNA at Week 48 (based on the Snapshot algorithm) for DTG+RPV versus CAR were -0.6 (95% CI: -4.3; 3.0) for SWORD-1 and 0.2 (95% CI: -3.9; 4.2) for SWORD-2 with a preset non-inferiority margin of -10%.
N = Number of subjects in each treatment arm
CAR = current antiretroviral regimen; DTG+RPV = dolutegravir plus rilpivirine; INI = Integrase inhibitor; NNRTI = Non-nucleoside reverse transcriptase inhibitor; PI = Protease Inhibitor
Effects on bone
In a DEXA substudy mean bone mineral density (BMD) increased from Baseline to Week 48 in subjects who switched to dolutegravir plus rilpivirine (1.34% total hip and 1.46% lumbar spine) compared with those who continued on treatment with a TDF-containing antiretroviral regimen (0.05% total hip and 0.15% lumbar spine. Any beneficial effect on fracture rate was not studied.
Pregnancy
No efficacy and safety data are available for the combination of dolutegravir and rilpivirine in pregnancy. Rilpivirine in combination with a background regimen was eva luated in a clinical trial of 19 pregnant women during the second and third trimesters, and postpartum. The pharmacokinetic data demonstrate that total exposure (AUC) to rilpivirine as a part of an antiretroviral regimen was approximately 30% lower during pregnancy compared with postpartum (6-12 weeks). Of the 12 subjects that completed the study, 10 subjects were suppressed at the end of the study; in the other 2 subjects an increase in viral load was observed postpartum, for 1 subject due to suspected suboptimal adherence. No mother to child transmission occurred in all 10 infants born to the mothers who completed the trial and for whom the HIV status was available. There were no new safety findings compared with the known safety profile of rilpivirine in HIV-1 infected adults.
In limited data from small numbers of women who received dolutegravir 50 mg once daily in combination with a background regimen, the total exposure (AUC) to dolutegravir was 37% lower during the 2nd trimester of pregnancy, and 29% lower during the 3rd trimester of pregnancy, compared with postpartum (6-12 weeks). Of the 29 subjects that completed the study, 27 subjects were suppressed at the end of the study. No mother to child transmission was identified. While 24 infants were confirmed to be uninfected, 5 were indeterminate due to incomplete testing, see sections 4.2, 4.4 and 5.2.
Paediatric population
The European Medicines Agency has deferred the obligation to submit the results of studies with Juluca in one or more subsets of the paediatric population in the treatment of HIV infection.
5.2 Pharmacokinetic properties
Jul |
