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.