To remember
- According to the French retrospective study DORAVIRconducted in real life, an antiretroviral regimen based on doravirine offers a good virological response, even if some factors seem to condition therapeutic success.
- Among them, being naive to any antiretroviral treatment is associated with a higher virological success than situations of switch or use after failure of a previous treatment.
- Infection with the emerging CRF02_AG subtype, high peak viral load, and initial presence of the V179D resistance mutation were among the main factors associated with virological failure.
Doravirine is an NNRTI (non-nucleoside reverse transcriptase inhibitor) indicated as part of triple therapy (fixed or free) against HIV-1 infection. It is recommended in combination with two nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs): in patients naïve to antiretroviral treatment, it should be combined with TDF (tenofovir disoproxil fumarate) and a XTC (lamivudine or emtricitabine) according to the European recommendationsbut the US authorities more readily recommend this triple therapy in specific situations, such as the desire to take only one treatment per day. Real-life data on this therapy would be useful to better understand the virological efficacy of this antiretroviral treatment and to understand the risk factors for virological failure or resistance. These two objectives were the subject of the DORAVIR study.
DORAVIR was conducted using retrospective data from 17 French centers between November 2020 and December 2022. In this study, patients infected with HIV-1 genotype were included. A total of 589 patients (68.1% male, 56.9% HIV-1 subtype B) were included, of whom 91.5% had already received antiretroviral treatment. The main combination with doravirine included TDF and lamivudine (70.6%).
The genetic sensitivity score remains essential to limit the emergence of mutations
Virologic success was achieved at 3 months in 88.3% of the population and at 6 months in 85.1%. Among those who had virologic failure, the median viral load was 2.1 and 2.3 log copies per milliliter at 3 and 6 months, respectively. Those who were antiretroviral treatment-naïve had higher virologic success (90.0% at 24 weeks) than those who switched treatment or those who had failed a previous treatment (88.4% and 63.4%, respectively).
According to multivariate analysis, patients infected with the CRF02_AG subtype, with a high peak viral load, with an initial V179D resistance mutation or those who had failed a previous antiretroviral therapy were associated with virologic failure. The authors note that V179D has been previously associated with reduced efficacy of other NNRTIs (nevirapine, efavirenz, etravirine). They suggest further studies to confirm these observations.
Among the group of patients who had switched treatment, risk factors associated with virological failure according to multivariate analysis were CRF02_AG viral subtype, high peak viral load, and the presence of the V179D mutation.
Overall, 9% of patients, or 14 of them, developed a median number of two resistance mutations. However, none of those with virological failure had resistance mutations when they were first prescribed antiretrovirals. According to the multivariate analysis, the initial genetic susceptibility score, established via Stanford’s resistance interpretation algorithm was associated with the emergence of resistance mutations.
