Doravirine-based first-line HIV therapy: non-inferior suppression, less weight gain, more bone loss

Design

Open-label, randomised, non-inferiority trial

Population

600 treatment-naive adults with HIV at 2 South African sites

Primary outcome

HIV RNA below 50 copies/mL at week 48

Effect

89.0% vs 90.7% (difference −1.7 points, 95% CI −6.6 to 3.1); weight gain 3.0 vs 5.0 kg

Weight gain after starting antiretroviral therapy, particularly with dolutegravir and tenofovir alafenamide, has become a real cardiometabolic concern. Opti-DOR randomised 600 treatment-naive adults at two South African sites — median age 34, about two-thirds women — to once-daily doravirine, lamivudine and tenofovir disoproxil fumarate (TDF) or dolutegravir, emtricitabine and tenofovir alafenamide (TAF). It was open-label and designed for non-inferiority on viral suppression.

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). Bone density fell more with the doravirine regimen: hip −2.1% against −0.5%, spine −3.2% against −1.3%. Of nine virological failures on doravirine, seven developed doravirine resistance; most resuppressed after switching to dolutegravir.

Dolutegravir-based therapy remains the WHO-preferred first-line regimen and its high barrier to resistance matters most where viral load monitoring is limited. The doravirine regimen is a reasonable alternative for people for whom weight gain is a priority concern, provided resistance testing and viral load follow-up are reliable. Some of the weight and bone differences reflect TDF versus TAF, not doravirine alone.

• Consider a doravirine, lamivudine and TDF regimen where weight gain is a major concern and monitoring is reliable.
• Keep dolutegravir-based therapy as the default where viral load monitoring or adherence support is limited.
• Check for baseline NNRTI resistance before starting doravirine, as the trial excluded high-level resistance.
• Expect more bone density loss with TDF-containing regimens; weigh this in people with osteoporosis risk.
• Check viral load early, because failure on doravirine usually brought resistance with it.

Why it matters

First-line HIV choice is starting to weigh long-term metabolic cost, not just suppression and resistance.

Don't overread it

A 2 kg difference at 48 weeks is a surrogate; the trial did not measure diabetes or cardiovascular events.

The statistics, in plain English

Non-inferiority was met because the lower bound of the suppression difference (−6.6 points) stayed above the pre-set −10 point margin. The weight difference of 2 kg has an interval of 1 to 3 kg, so the effect is real but modest.

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