Background:
Integrase strand transfer inhibitors (INSTIs) and tenofovir alafenamide–based regimens are potentially associated with weight gain and metabolic perturbations in people living with HIV (PLWH). Cabotegravir (CAB), an INSTI, plus rilpivirine (RPV), a non-nucleoside reverse transcriptase inhibitor, administered monthly or every 2 months (Q2M) is the first complete long-acting (LA) regimen recommended by treatment guidelines for the maintenance of HIV-1 virologic suppression. Modest body weight and lipid changes have been observed in participants receiving CAB+RPV LA therapy in Phase 3/3b studies. SOLAR (NCT04542070) is a Phase 3b noninferiority efficacy study, also evaluating weight and metabolic changes from baseline (BL) to Month (M)11/12 as additional endpoints, in PLWH switching to CAB+RPV LA Q2M vs. continuing on bictegravir/emtricitabine/tenofovir alafenamide (B/FTC/TAF).
Methods:
Among 687 participants randomized (2:1; n=6 not dosed), 454 switched to CAB+RPV LA Q2M (175 elected for oral lead-in [OLI] and 279 elected for therapy without an OLI) and 227 continued on B/FTC/TAF. Changes from BL in body weight, body mass index (BMI) category, waist and hip circumferences (WC, HC), waist-to-height ratio (WHtR), waist-to-hip ratio (WHR), muscle mass, total body fat, and proportion of participants with insulin resistance or metabolic syndrome were analyzed at M11 (LA without OLI)/M12 (LA with OLI and B/FTC/TAF).
Results:
Median (interquartile range) change in body weight from BL was –0.40 kg (–2.95, 2.10) in the LA arm and +0.05 kg (–2.30, 1.95) in the B/FTC/TAF arm at M11/12 (Table). Mean (standard deviation) change in WC and HC was +0.19 cm (8.01) and +0.26 cm (7.81) in the LA arm, and +1.64 cm (9.19) and +0.51 cm (11.44) in the B/FTC/TAF arm at M11/12. There were no clinically relevant changes from BL to M11/12 in participants’ WHtR, WHR, or the proportion of participants with metabolic syndrome, abdominal obesity, or insulin resistance in either arm.
Conclusions:
This is the first randomized Phase 3b study to compare weight, anthropometric, and metabolic changes in a standardized manner among PLWH switching to CAB+RPV LA Q2M or continuing B/FTC/TAF. Changes in weight, BMI, and body composition measurements were minor and similar between treatment arms through M11/M12. There were no clinically relevant changes in the proportion of participants with metabolic syndrome, abdominal obesity, or insulin resistance between arms at M11/12.
Baseline Characteristics, Weight, and Metabolic Changes Through Month 11 or Month 12 From SOLAR