DORAL: doravirine plus raltegravir, once daily, held suppression in 114 adults

Design

Randomised 2:1 open-label phase 2 switch trial in three countries

Population

114 virologically suppressed adults with HIV-1, median age 57

Primary outcome

Virological failure (HIV-1 RNA 50 copies/mL or more, confirmed) at week 48

Effect

1 failure (1.3%, 95% CI 0.0 to 6.9) in the immediate-switch arm; none in the delayed-switch arm

DORAL was a multicentre, open-label, randomised phase 2 trial in France, Italy and Spain. Virologically suppressed adults on stable antiretroviral therapy, without prior doravirine and without raltegravir resistance, were randomised 2:1 to switch immediately to doravirine 100 mg plus raltegravir 1200 mg once daily or to continue their regimen and switch at week 48. Median age was 57 and median duration of suppression was 10 years.

In the 114 participants, one virological failure occurred by week 48 in the immediate-switch group (1.3%, 95% CI 0.0 to 6.9) and none in the delayed-switch group. No further failure occurred through week 96. Three treatment-related adverse events led to discontinuation. In a genital sub-study, drug concentrations exceeded inhibitory thresholds in most samples.

The authors position the regimen for selected people, notably where drug interactions or avoiding nucleoside analogue exposure matter. It is a proof-of-concept phase 2 study without a comparator over the full period.

• This two-drug regimen suits selected, long-suppressed patients without raltegravir resistance.
• It is chosen mainly to limit interactions or avoid nucleoside analogue exposure.
• Check for prior resistance before switching.
• Use specialist HIV advice for the decision; this is phase 2 evidence.

Why it matters

It gives patients in whom interactions or nucleoside analogue exposure are a concern another option to discuss.

Don't overread it

Phase 2, open-label, 114 participants, selected for no prior resistance and with a long period of suppression.

The statistics, in plain English

One failure in about 76 switched patients gives 1.3%, but the confidence interval runs to 6.9%, so a failure rate of several percent cannot be excluded. A single event cannot establish equivalence with standard therapy.

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