Add-on efficacy of doravirine in PLWHIV with virological failure and low-level viremia

Doravirine is a non-nucleoside reverse transcriptase inhibitor (NNRTI) with moderate plasma protein binding and good potential for anatomical sanctuary penetration.

Adding doravirine to existing antiretroviral therapy (ART) regimens has led to virological success in two groups of people living with HIV (PLWHIV): those with recent virological rebound (n = 84) and those with prolonged low-level viremia (LLV, n = 39). Doravirine was added without any modification to the other ART drugs.

After 6 months, 88% of PLWHIV in the recent failure group had achieved virological success, compared to 33% of those in the LLV group. Efficacy was closely tied to the genotypic susceptibility score (GSS), with higher success rates in patients whose regimens retained two or more active drugs. Doravirine resistance mutations were uncommon but occurred more frequently in the LLV group. No significant associations were found between treatment response and CD4 count, nadir, VL zenith or duration of suppression.

These findings support the use of doravirine add-on strategies to rescue virological control without changing the full regimen, particularly when a full regimen change is not feasible and when GSS is favourable. The study highlights the potential of doravirine in tailored salvage therapy strategies.