Hernandez B, Kahl L, Matthews J, Vincent T, Angelis K, Koteff J, Jones CB, Wynne B, Aboud M

Affiliates

A(1), B(2), C(3), D(2), E(4), F(3), G(2), H(5), I(2) 1- ViiV Healthcare, Tres Cantos, Spain 2- ViiV Healthcare, Brentford, UK 3- ViiV Healthcare, Research Triangle Park, NC, USA 4 - GlaxoSmithKline, Uxbridge, UK 5- ViiV Healthcare, Collegeville, Pennsylvania, USA

Abstract

Background: Treatment modalities that reduce long term cumulative ARV exposure in the form of 2-drug regimens (2DR) are an area of active research. DTG + RPV as a 2DR for the maintenance of virologic suppression was non-inferior to 3DRs at week (Wk) 48 in SWORD 1&2 studies and has reported durable efficacy to Wk 100. We summarize the impact on bone, renal and inflammatory biomarkers through to Wk 100.

Methods: Two identical open-label, multicenter, randomized, phase III, non-inferiority studies demonstrated the efficacy and safety of switching from CAR to DTG + RPV once daily in HIV-1-infected adults, with HIV-1 RNA< 50c/mL for at least 6 months and no history of virologic failure. Participants were randomized 1:1 to switch immediately to DTG + RPV (Early Switch group) or continue CAR. Participants randomised to CAR with confirmed suppression at Wk 48 switched to DTG + RPV at Wk 52 (Late Switch group). Additional endpoints included change from Baseline to Wk 100 for bone, renal, inflammatory and atherogenesis biomarkers quantitated on cryopreserved samples.

Results: Of 1024 participants randomized and treated with DTG + RPV or CAR, 892 (87%) completed the Wk 100 study visit. Durable suppression 89% (n=513) was reported up to Wk 100 in the Early Switch Group; suppression rates were consistent among the Late Switch Group 93% (n=477) with that seen within the Early Switch Group at Week 48 (95%, n=513). Bone biomarkers: The Early Switch Group had a significant decrease from baseline to Wk 48 in markers of bone turnover (type-1 collagen C-telopeptide, bone specific alkaline phosphatase, osteocalcin and procollagen 1 N-terminal propeptide). This decrease was maintained in 3 of the 4 markers at Wk 100. Significant decreases in all bone biomarkers were observed in the Late Switch Group. Renal biomarkers: Significant decreases in urinary retinol binding protein/creatinine ratio were maintained to Wk 100 in the Early Switch Group and post switch in the Late Switch Group. Inflammatory and atherogenesis biomarkers (C-reactive protein, D-dimer, Interleukin-6, soluble (s) CD14, sCD163, FABP-2 and sVCAM-1): DTG + RPV was associated with a neutral effect on inflammatory and atherogenesis biomarkers with no clear pattern of change noted at either Wk 48 or Wk 100 as compared to baseline.

Conclusion: Together, these data indicate that the switch to the 2DR of DTG + RPV through Wk 100 is associated with improvement in markers of bone health, a favorable effect on renal tubular function and has a neutral impact on biomarkers of inflammation and atherogenesis, while preserving virologic suppression.