Opti-DOR: doravirine regimen non-inferior to dolutegravir with 2 kg less weight gain

Design

Open-label randomised non-inferiority trial, 48 weeks

Population

600 treatment-naive adults with HIV at two South African sites

Primary outcome

HIV RNA below 50 copies/mL at week 48

Effect

89.0% vs 90.7% (difference -1.7, 95% CI -6.6 to 3.1); weight +3.0 vs +5.0 kg

Opti-DOR, published in JAMA on 20 October 2026, randomised 600 treatment-naive adults at two South African sites to once-daily doravirine, lamivudine and tenofovir disoproxil fumarate, or dolutegravir, emtricitabine and tenofovir alafenamide. Participants were almost all Black African, two-thirds were women, and the median age was 34. Those with high-level baseline doravirine resistance were excluded.

At 48 weeks, 89.0% on the doravirine regimen and 90.7% on the dolutegravir regimen had HIV RNA below 50 copies/mL (difference -1.7 points, 95% CI -6.6 to 3.1), meeting non-inferiority. Median weight gain was 3.0 kg against 5.0 kg (difference -2.0 kg, 95% CI -3.0 to -1.0). Hip and spine bone density fell more on the doravirine regimen, as expected with tenofovir disoproxil. Of 9 virological failures on doravirine, 7 developed doravirine resistance; most resuppressed on dolutegravir.

This gives an alternative for people where weight gain is the main concern, but it trades weight for bone and has a lower barrier to resistance than dolutegravir. It applies most directly to settings similar to the trial population.

• Consider a doravirine-based regimen when weight gain is a major concern at ART initiation, after resistance testing.
• Check baseline resistance before using doravirine; failures on it often selected resistance.
• Weigh the larger fall in bone density with tenofovir disoproxil, particularly in people with osteoporosis risk.
• Keep dolutegravir-based therapy as the default where adherence is uncertain, given its higher barrier to resistance.
• Monitor weight at every visit on any first-line regimen.

Why it matters

Weight gain on integrase-based therapy is a real cardiometabolic concern, and this is a randomised alternative that keeps suppression.

Don't overread it

Weight was a secondary outcome; the trial was powered for viral suppression, and lasted 48 weeks.

The statistics, in plain English

Non-inferiority means the doravirine regimen was not worse by more than 10 points; the whole interval (-6.6 to 3.1) sits inside that margin. The 2 kg weight difference has an interval clear of zero.

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