Title

Renal safety parameters after switch to doravirine/islatravir (DOR/ISL 100/0.75mg) once-daily: week 48 results from 2 randomized, active-controlled phase 3 trials, MK8591A-017 (P017) and MK8591A-018 (P018)

Presenter

Frank A. Post

Authors

F.A. Post¹, J.-M. Molina², A.M. Mills³, K. Lacombe⁴, J.K. Rockstroh⁵, C.J. McMullan⁶, Y.-P. Zhou⁶, A. Grandhi⁶, F.-H. Su⁶, A.J. Kim⁶, M.C. Fox⁶, T.A. Correll⁶

Institutions

¹King's College Hospital NHS Foundation Trust, London, United Kingdom, ²University of Paris Diderot and St-Louis Hospital, Paris, France, ³Men's Health Foundation, Los Angeles, United States, ⁴INSERM IPLESP, St. Antoine Hospital, AP-HP, Sorbonne Université, Paris, France, ⁵Medizinische Klink und Poliklinik, University of Bonn, Bonn, Germany, ⁶Merck & Co., Inc., Rahway, United States

BACKGROUND: Certain antiretroviral drugs may affect renal function. The objective of this post-hoc analysis was to evaluate renal safety parameters after 48 weeks in 2 phase 3 DOR/ISL (100/0.75mg) switch trials.
METHODS: P017 (NCT04223778) was an open-label switch from any oral 2- or 3-drug regimen, with randomization stratified by baseline antiretroviral therapy (bART). P018 (NCT04223791) was a double-blind switch; bART was bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF). Adults with HIV-1 were randomized 1:1 to switch to DOR/ISL (100/0.75mg) once-daily or continue bART. Participants with creatinine clearance=30 mL/min were excluded. Renal safety parameters were assessed, including estimated glomerular filtration rate (eGFR) using CKD-Epi Cystatin-C equation to avoid reliance on creatinine-based eGFR confounded by inhibition of renal creatinine secretion by several antiretroviral agents.
RESULTS: 658 participants switched to DOR/ISL (100/0.75mg); 655 remained on bART, of which 319 remained on B/F/TAF in P018. In P017, bART was InSTI-based in 52%, PI-based in 14%, and Other in 34% of participants; 30% of bART included TDF, 39% included TAF, and 28% included other NRTIs. No differences in mean change from baseline between treatment arms were observed for cystatin-C or urine albumin/creatinine ratio in either trial at 48 weeks. An increase in cystatin-C based eGFR and a decrease in urine retinol-binding protein/creatinine ratio (URBP/UC) was observed in P017 for participants switched to DOR/ISL; a similar effect was not present in P018 (Table). Renal and urinary adverse events (RUAEs) were infrequent and similar between groups: P017 DOR/ISL 3.9%, bART 2.4%; P018 DOR/ISL 2.2%, B/F/TAF 3.4%; no participants switched to DOR/ISL had serious RUAEs or discontinued treatment due to RUAEs.
CONCLUSIONS: Overall, DOR/ISL (100/0.75mg) had no adverse impact on renal function after 48 weeks in participants who switched from bART across 2 phase 3 trials. Switching off certain bART in P017 may account for mild improvements observed in URBP/UC and eGFR with DOR/ISL.

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