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Title
Weight and body composition 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
Grace A. McComsey
Authors
G.A. McComsey1, J.-M. Molina2, A.M. Mills3, J.K. Rockstroh4, S. Walmsley5, R. Mngqibisa6, D. Braun7, Y.-P. Zhou8, S.O. Klopfer8, A. Grandhi8, F.-H. Su8, M.C. Fox8, A.J. Kim8, T.A. Correll8
Institutions
1Case Western Reserve University, Cleveland, United States, 2University of Paris Cité, Paris, France, 3Men's Health Foundation, Los Angeles, United States, 4University Hospital Bonn, Department of Medicine I, Bonn, Germany, 5University Health Network, University of Toronto, Department of Medicine, Toronto, Canada, 6Enhancing Care Foundation, Wentworth Hospital, Durban, South Africa, 7University of Zurich, Institute of Medical Virology, Zurich, Switzerland, 8Merck & Co., Inc., Rahway, United States

BACKGROUND: Some components of approved antiretroviral therapies (ART) are associated with weight gain and/or lipodystrophy (peripheral lipoatrophy and/or central fat hypertrophy). We evaluated changes in weight and body composition 48 weeks after switch to once-daily DOR/ISL (100/0.75mg) in two phase 3 studies.
METHODS: P017 (NCT04223778) was an open-label study in adults receiving any oral 2- or 3-drug ART regimen. P018 (NCT04223791) was a double-blind study in adults receiving bictegravir/emtricitabine/ tenofovir alafenamide (B/F/TAF). Participants with HIV-1 RNA <50 copies/mL were randomized (1:1) to switch to once-daily DOR/ISL (100/0.75mg) or to continue baseline ART (bART) (P017) or B/F/TAF (P018); P017 randomization was stratified by bART, which was PI-based in 14% of participants, InSTI-based in 52%, and Other (mainly NNRTI-based) in 34%. Peripheral fat and trunk fat were measured by DEXA scan and were evaluated by a central imaging reader.
RESULTS: 658 participants switched to DOR/ISL (100/0.75mg), 336 remained on bART, and 319 remained on B/F/TAF. Baseline weight differed by prior regimen in P017 (Table). Mean weight gain was similar for DOR/ISL vs continued B/F/TAF or other InSTI-based regimens but was higher for DOR/ISL vs continued PI-based or NNRTI-based regimens (Table). Mean changes from baseline in peripheral and trunk fat were similar for DOR/ISL vs continued B/F/TAF in P018 but were higher for DOR/ISL vs continued bART in P017 (Table). In a post hoc analysis of P017, mean increases in weight, peripheral fat, and trunk fat were higher for DOR/ISL vs continued bART containing efavirenz (EFV) and/or TDF but were similar for DOR/ISL vs continued non-EFV/non-TDF regimens (Table).
CONCLUSIONS: Changes in weight and body fat after switch to DOR/ISL were similar to continuing bART, except among participants who switched from EFV and/or TDF, which are known to suppress weight gain. Switching from InSTI-based regimens to DOR/ISL did not reduce weight over 48 weeks.