Switching to a NRTI-free 2 drug regimen (2DR) –a sub-analysis of the 48 weeks DUALIS study on metabolic and renal changes

Abstract Background/Aims: Switching from a three-drug regimen (3DR: boosted darunavir [bDRV] and two nucleoside reverse transcriptase inhibitors [NRTIs]) to a two-drug regimen (2DR: bDRV and dolutegravir [DTG]) demonstrated non-inferiority with regard to viral suppression in people living with HIV (PLWH) in the DUALIS study. This sub-analysis focuses on changes in metabolic and renal parameters when sparing the NRTI backbone. Methods: DUALIS was a randomized, open-label, multicenter (27) phase 3-trial. Participants were virologically suppressed (HIV-RNA < 50 copies/mL) on 3DR for at least 24 weeks. Subjects were either switched to DTG 50 mg + bDRV 800 mg (with ritonavir 100 mg) (2DR) or continued their regimen consisting of two NRTIs in combination with ritonavir-bDRV (3DR) once daily. Data of metabolic and renal parameters at baseline and week 48 were compared. Results: The LDL-fraction increased by + 13.3 (−3.0 to +31.3) mg/dL on 2DRs and was stable (−14.0 to +18.0 mg/dL) on 3DRs (p < 0.0010). PLWH gained +2.0 (−0.2 to +4.0) kg and +0.2 (−1.9 to +2.1) kg in body weight on 2DRs and 3DRs, respectively 3 (p = 0.0006). The MDRD eGFR decreased by −7,8 (−17.4 to −0.3) mL/min/1.73m2 and 0.4 (−8.8 to +5.7) mL/min/1.73m2 on 2DRs and 3DRs, respectively (p = 0.0002), while serum levels of cystatin C were stable in both arms (2DR: −0.1 to +0.1 mg/L; 3DR: 0.0 to +0.1 mg/L). Conclusions: While being non-inferior in terms of viral suppression, sparing the NRTI backbone showed a non-favorable profile in metabolic or renal parameters over 48 weeks.