- Design
- Phase 2, randomised 2:1, open-label, multicentre
- Population
- 114 virologically suppressed adults with HIV-1, median suppression 10 years
- Primary outcome
- Virological failure (confirmed HIV-1 RNA ≥50 copies/mL) at week 48
- Effect
- 1.3% (95% CI 0.0–6.9) immediate switch; no further failures to week 96
DORAL randomised 114 adults in France, Italy and Spain who had been virologically suppressed for a median of ten years, two to one, to switch at once to once-daily doravirine 100 mg with raltegravir 1,200 mg, or to switch after 48 weeks. Median age was 57 and CD4 count 700.
One participant in the immediate-switch group had virological failure by week 48 and none in the delayed group; no further failures occurred to week 96. Three adverse events led to stopping. In a genital sub-study, drug concentrations mostly exceeded inhibitory thresholds.
From a pharmacology standpoint the regimen is attractive because both drugs have few interactions: doravirine is a CYP3A substrate without being an inhibitor or booster, and raltegravir is glucuronidated. That suits older patients on statins, anticoagulants or anticancer drugs, and those with NRTI-related bone or kidney concerns. This is a small phase 2 trial in a selected, stable population, and doravirine is still a CYP3A substrate, so strong inducers such as rifampicin and carbamazepine remain contraindicated.
- Consider doravirine plus raltegravir for selected long-suppressed patients where NRTI toxicity or interactions are a concern.
- Check for raltegravir resistance history and prior NNRTI failure before switching.
- Avoid strong CYP3A inducers, including rifampicin, carbamazepine and phenytoin, with doravirine.
- Recheck viral load four to eight weeks after any regimen switch.
Why it matters
It offers an option built around minimising interactions for an ageing, polymedicated HIV population.
Don't overread it
A phase 2 proof-of-concept study cannot show non-inferiority to standard three-drug regimens.
The statistics, in plain English
One failure in 76 patients gives a rate of 1.3%, but the confidence interval runs to 6.9%, which shows how little a trial of this size can exclude. Larger trials would be needed to compare it with standard regimens.
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