Initial HIV Therapy for Adults and Treatment-Associated Weight Gain: The Opti-DOR Randomized Clinical Trial.

In 30 seconds

The Opti-DOR open-label, noninferiority randomized trial compared two initial antiretroviral regimens in 600 ART-naive adults at two South African sites; 99.5% of participants were Black African. At week 48, viral suppression was achieved by 89.0% with doravirine, lamivudine, and tenofovir disoproxil fumarate and 90.7% with dolutegravir, emtricitabine, and tenofovir alafenamide, meeting the prespecified noninferiority margin. Median weight gain was 3.0 kg versus 5.0 kg, respectively (between-group difference, -2.0 kg [95% CI, -3.0 to -1.0 kg]; P < .001).

Key findings

• Week-48 viral suppression was 89.0% vs 90.7%; the between-group difference was -1.7 percentage points (95% CI, -6.6 to 3.1), meeting the -10 percentage-point noninferiority margin.
• Median weight gain was 3.0 kg with doravirine-based therapy vs 5.0 kg with dolutegravir-based therapy (difference, -2.0 kg [95% CI, -3.0 to -1.0 kg]; P < .001).
• Hip and spine bone mineral density declined more with doravirine, lamivudine, and tenofovir disoproxil fumarate than with the comparator regimen (P < .001 for each comparison).
• Doravirine resistance emerged in 7 of 9 participants with virologic failure in the doravirine-based group.

Why it matters

Weight gain after ART initiation may add to cardiometabolic risk. This trial found less median weight gain with the doravirine-based regimen while maintaining noninferior viral suppression at 48 weeks. The greater bone mineral density declines and emergence of doravirine resistance in some participants with virologic failure are also relevant when weighing the observed differences between regimens.

What to keep in mind

Follow-up reported here was 48 weeks, so longer-term weight, bone, and virologic outcomes are not established. The trial was conducted at two South African sites and enrolled a predominantly Black African population.