Energy balance and body composition after switch between integrase strand transfer inhibitors and doravirine among people with HIV

Abstract Background Integrase strand transfer inhibitors (INSTIs) are associated with excessive weight gain among a subset of persons with HIV (PWH), due to unclear mechanisms. We assessed energy intake (EI) and expenditure (EE) following switch off and onto INSTIs. Methods PWH with >10% weight gain on an INSTI-based regimen switched INSTI to doravirine for 12 weeks, then back to INSTI for 12 weeks while keeping their remaining regimen stable. Twenty-four-hour EE, EI and weight were measured on INSTI, following switch to doravirine, and upon INSTI restart. Mixed models analysed changes over time. Results Among 18 participants, unadjusted 24 h EE decreased by 83 (95% CI −181 to 14) kcal following switch to doravirine, and by 2 (−105 to 100) kcal after INSTI restart; energy balance (EE−EI) increased by 266 (−126 to 658) kcal from Week 0 to Week 12, and decreased by 3 (−429 to 423) kcal from Week 12 to Week 24. Trends toward weight loss occurred following switch to doravirine [mean −1.25 (−3.18 to 0.69) kg] and when back on INSTI [−0.47 (−2.45 to 1.52) kg]. Trunk fat decreased on doravirine [−474 (−1398 to 449) g], with some regain following INSTI restart [199 (−747 to 1145) g]. Fat-free mass decreased on doravirine [−491 (−1399 to 417) g] and increased slightly after INSTI restart [178 (−753 to 1108) g]. Conclusions Among PWH with >10% weight gain on an INSTI, switch to doravirine was associated with a trend towards decreases in 24 h EE, weight, trunk fat mass and fat-free mass. Observed changes were not significant, but suggest a mild weight-suppressive effect of doravirine among PWH.