Improvement in insulin sensitivity after switching from an integrase inhibitor‐based regimen to doravirine/tenofovir disoproxil fumarate/lamivudine in people with significant weight gain.

Objectives: We performed an observational, retrospective, cohort study to assess changes in insulin sensitivity after a switch from dolutegravir/lamivudine (DOL/3TC) or bictegravir/emtricitabine/tenofovir alafenamide (BIC/F/TAF) to doravirine/tenofovir disoproxil fumarate/3TC (DOR/TDF/3TC) in virologically suppressed people living with HIV with recent significant weight gain. Methods: All non‐diabetic patients with HIV treated with DOL/3TC or BIC/F/TAF for ≥12 months, with HIV RNA <20 copies/mL, and with a weight increase ≥3 kg in the last year, who underwent a switch to DOR/TDF/3TC were enrolled into the study. Serum levels of glucose, insulin, and homeostasis model assessment of insulin resistance (HOMA‐IR) index were evaluated every 6 months during a 12‐month follow‐up. Results: Overall, 81 patients were enrolled: 41 were treated with DOL/3TC and 40 with BIC/F/TAF. At baseline, median HOMA‐IR index was 3.18 and insulin resistance (HOMA‐IR index >2.5) was present in 49 subjects (60%). At 12 months after the switch to DOR/TDF/3TC, change in mean serum glucose concentration was not significant, but the reduction in median concentration of insulin was significant (−3.54 mcrUI/L [interquartile range −4.22 to −2.87]; p = 0.012), associated with a significant reduction in mean HOMA‐IR index (−0.54 [interquartile range −0.91 to −0.18]; p = 0.021). A significant reduction in total and low‐density lipoprotein cholesterol was also reported, whereas decreases in mean body weight and mean body mass index were not significant. Conclusions: In our retrospective study in virologically suppressed people living with HIV treated with DOL/3TC or BIC/F/TAF and with recent weight gain, the switch to DOR/TDF/3TC led to a significant improvement in insulin sensitivity and plasma lipids, with a trend to decreased body weight. [ABSTRACT FROM AUTHOR]