2D-STUDY

Fundació de Lluita contra la SIDA, les Malalties Infeccioses i la Promoció de la Salut i La Ciència

S/N Carretera de Canyet, Badalona, Spain,

Project Manager, Fundació Lluita contra les Infeccions, +34 93497 84 14, jtoro@fls-rs.com

Project Manager, Fundació Lluita contra les Infeccions, +34 93497 84 14, jtoro@fls-rs.com

No

No

No

Final

10 Aug 2021

Yes

10 Aug 2021

Yes

10 Aug 2021

No

To evaluate and compare the efficacy of DTG plus DRV/cobi bitherapy as a once-daily simplification strategy versus maintenance of the current antiretroviral regimen in maintaining virological suppression (RNA HIV-1 < 50 copies/mL) at Week 48 (by Time to Loss of Virological Response, TLOVR) in well suppressed and highly experienced patients harboring archived DRM against at least two antiretroviral classes.

When 75% of the planned sample has been enrolled and has reached its Week 12 visit, an interim efficacy review will be done by an independent Data Monitoring Committee (Internal DMC), to ensure the rate of virologic failure is not unacceptably high. An efficacy rate (by TLOVR) of < 80% will be considered unacceptable and cause the study to be prematurely stopped.

01 Jun 2018

No

Yes

Spain: 89

89

89

0

0

0

0

0

0

89

0

0

Overall Trial (overall period)

Randomised - controlled

Yes

Dolutegravir

DTG QD

Tablet

Oral use

Dosage: 50 mg daily. Administration details: Orally administered during the 48 weeks of follow-up.

Darunavir/cobicistat

DRV/Cobi QD

Tablet

Oral use

dosage: 800/150 mg od DRV/Cobi QD Administration details: Orally administered during the 48 weeks of follow-up

Triple Antiretroviral Therapy

NRTI, NNRTI, NRTIs, PIs, INI, CCR5 Receptor antagonist

Tablet

Oral use

The formulation of the study products will be the commercial one. Both treatments will be orally administered during the 48 weeks of follow-up.

Overall Trial

Experimental Arm

Control Group

ITT analysis set

ITT analysis set included 89 subjects: 45 in the 2D group and 44 in the SOC group

Virologic failure was defined as detection of HIV-1 RNA ≥50 copies/mL at 2 consecutive visits measured within 2 to 4 weeks or as a single determination of HIV-1 RNA ≥50 copies/ mL followed by premature treatment discontinuation. A genotyping test was performed at virologic failure confirmation. If adverse events resulted in treatment discontinuation or dropout, they were treated as virologic failure for efficacy assessment. The Kaplan-Meier estimation was used to describe TLOVR analysis for all participants and by treatment arm.

Primary

At week 48

In the primary efficacy analysis, the Kaplan–Meier estimator will be used to describe the TLOVR, for all patients and by the treatment arms

Experimental Arm v Control Group

89

Pre-specified

12.5

2-sided

Standard deviation

0.05

In the 2D group, 3 patients experienced adverse events leading to treatment discontinuation, and an additional 3 patients were lost to follow-up, as opposed to none in the SOC group.

Secondary

At week 48

The proportion with HIV-1 RNA <50 copies/mL at week 48 according to the FDA snapshot was evaluated. In the FDA snapshot analysis, participants were classified according to 3 outcomes: Responders: HIV-1 RNA <50 copies/mL at week 48 Nonresponders: HIV-1 RNA ≥50 copies/mL at week 48— participants with virologic failure or blips (in window) or participants who discontinued the study drug because of adverse events, death, or other reasons before week 48 with last available HIV-1 RNA ≥50 copies/mL No virologic data: participants who discontinued the study drug before week 48 for reasons other than low efficacy, including adverse event and death with last available HIV-1 RNA <50 copies/mL, and participants who were still taking the study drug but for whom HIV-1 RNA data were missing at week 48

Secondary

at week 48

The median (IQR) change from baseline in CD4+ cell count at week 48 was −1.0 cells/mm3 (−2.9 to 0.5) in the 2D arm and 0.4 cells/mm3 (−2.7 to 2.8) in the SOC arm (P = .130)

Secondary

At week 48

Participants had a median 3 (2–8) and 5 (4–7) associated DRMs in the genes of protease and reverse transcriptase, respectively

Secondary

At 48 weeks

The median change in total cholesterol from baseline was −0.8 mg/dL (−19.3 to 26.0) in the 2D group and 3.00 mg/dL (−10.0 to 15.5) in the SOC group (P = .970). Median changes in low- and high-density lipoprotein cholesterol were 0.0 mg/dL (−26.6 to 24.0) and −1.1 mg/dL (−6.4 to 4.4) in the 2D group and −2.3 mg/dL (−19.0 to 16.0) and −2.0 mg/dL (−5.4 to 2.8) in the SOC group (P = .590 and P = .740), respectively. Triglyceride levels did not show significant changes, with a median change of −7.0 mg/dL (−35.3 to 60.0) in the 2D group and 10.0 mg/dL (−17.3 to 40.6) in the SOC group (P = .570).

Secondary

At week 48

From 01-Jun-2018 to 10-Aug-2021

10

Experimental Group

Control Group