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INFLAMMATORY AND ATHEROGENESIS MARKERS 148 WEEKS POSTSWITCH TO DTG+RPV IN SWORD-1/ -2
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CROI 2021 March 6-10 Reported by Jules Levin
Josep María Llibre1, Luis Fernando Lopez Cortes2, Alicia Aylott3, Brian Wynne4, Jessica Matthews4, Jean A. Van Wyk5, Lesley P. Kahl5
1Hospital Universitari Germans Trias i Pujol, Barcelona, Spain, 2Hospital Universitario Virgen del Rocío, Sevilla, Spain, 3GlaxoSmithKline, Uxbridge, UK, 4ViiV Healthcare, Research Triangle Park, NC, USA, 5ViiV Healthcare, Brentford, UK
Background: The SWORD studies demonstrated noninferiority post-switch to the 2-drug regimen (2DR) dolutegravir (DTG) + rilpivirine (RPV) vs 3- or 4-drug current antiretroviral therapy (CAR) at Week (W) 48 and maintained viral suppression to W148. Evaluation of whether switching from CAR to DTG+RPV influences markers of inflammation and atherogenesis is an area of current interest.
Methods: Adults with suppressed HIV-1 RNA were randomized to DTG+RPV (Early Switch [ES] group) or continue CAR. CAR participants (pts) suppressed at W48 switched to DTG+RPV at W52 (Late Switch [LS] group). Biomarkers of inflammation and atherogenesis were evaluated from Baseline (BL) to W48 for DTG+RPV and CAR and non-comparatively for DTG+RPV post-switch through W148.
Results:1024 pts were randomized across both studies and exposed to DTG+RPV (n=513) or CAR (n=511). Regarding inflammatory markers through W48, participants on CAR had a greater increase in sCD14 (P<0.0001) vs those on DTG+RPV. No other significant changes from BL to W48 were observed between pts receiving DTG+RPV and CAR. Longitudinally to W148, no significant change in C-reactive protein was observed in the ES and LS groups. Increases in the ES group in sCD14 at W48 and W100 and decreases in the LS group at W100 were observed, although both groups showed significant decreases in sCD14 at W148 (P<0.001). A similar inconsistent pattern of change was observed longitudinally in ES and LS groups for interleukin-6 and sCD163; however, pooled SWORD data showed significant increases in sCD163 at W148 in both groups (P<0.001). Overall, no consistent reproducible pattern of change was seen post-switch across markers (Figure). Regarding atherogenesis markers, in both SWORD studies, FABP-2 and sVCAM-1 for the ES and LS groups showed consistent significant, sustained reductions post-switch to DTG+RPV through W148 (P<0.001) except for a nonsignificant reduction in sVCAM-1 in the ES group at W48. Change from BL to W148 in D-dimer was inconsistent across SWORD-1/-2 and the ES and LS groups at W100; however, significant increases from BL at W148 (P<0.001) was observed in both groups across both studies.
Conclusion: In the controlled ES phase, no significant differences between arms were observed at W48 except for sCD14 favoring DTG+RPV. Longitudinally up to W148, there was no consistent, reproducible pattern of change post-switch, providing no evidence of increased inflammation or atherogenesis markers on the 2-drug regimen, DTG+RPV, while maintaining viral suppression.
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