Factors Associated With Weight Change After Continuing or Switching to a Doravirine-based Regimen

Factors associated with weight change were examined in phase 3 studies in which adults living with HIV-1 continued or switched to doravirine-based antiretroviral regimens.

Participants were randomized to first-line therapy with doravirine or darunavir/ritonavir, each given with 2 nucleos(t)ide reverse transcriptase inhibitors (NRTIs) (DRIVE-FORWARD) and to doravirine/lamivudine/tenofovir disoproxil fumarate (TDF) or efavirenz/emtricitabine/TDF (DRIVE-AHEAD); after 96 weeks, participants continued (n = 466) or switched to (n = 423) doravirine for 96-week open-label extensions. In DRIVE-SHIFT, virologically suppressed participants on stable antiretroviral therapy were randomized to switch to doravirine/lamivudine/TDF at day 1 or week 24 through week 144 (n = 535). Generalized logistic models were used to analyze factors associated with weight loss (≥5% decrease), stable weight (<5% change), and weight gain (≥5% increase) after continuation or switch.

Most participants who continued or switched to doravirine also received TDF (>74%) and had stable weight (>57%). Weight loss (odds ratio [OR], 6.14) or stable weight (OR, 2.15) was more common in participants of non-Black versus Black heritage after switching to doravirine. More participants switching from weight-suppressive non-nucleoside reverse transcriptase inhibitors versus protease inhibitors experienced weight gain versus weight loss in DRIVE-SHIFT (OR, 0.41) and weight gain versus stable weight in DRIVE-FORWARD and DRIVE-AHEAD (OR, 0.60). No significant association between weight change and prior NRTI use was observed in DRIVE-SHIFT.

Overall, switching to doravirine was weight neutral, although weight change may differ by demographics and weight-suppressive properties of a prior regimen. More research in historically underrepresented groups may help explain these findings.

NCT02275780, NCT02403674, NCT02397096.