Changes in NNRTI use have not altered the ecology of NNRTI resistance over the last 10 years in people with HIV experiencing virological failure on antiretroviral drugs

Background: We aimed to determine how non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance profiles have changed over the last decade in people living with HIV (PLWHIV) experiencing virological failure on all antiretroviral treatments, including different NNRTIs.

Materials and methods: We analysed the use of the different NNRTIs in PLWHIV treated with antiretroviral drugs at an academic centre and the HIV NNRTI resistance profiles observed in cases of virological failure over the last 10 years (2014-23). We used the latest ANRS-MIE algorithm (v33; https://hivfrenchresistance.org/) to analyse the resistance mutation profiles of the HIV reverse transcriptase sequences.

Results: During this period, the frequency of NNRTI use remained high, fluctuating slightly between 43.5% (n = 1782/4094) and 39.9% (n = 1758/4421). The use of efavirenz (10.8%-1.5%), nevirapine (7.0%-1.2%), and etravirine (11.0%-1.1%) decreased, whereas the use of rilpivirine (14.7%-26.3%) and doravirine (available from 2018, rising to 9.7% in 2023) increased. These trends were statistically significant for etravirine (P = 0.033) and rilpivirine (P < 0.001). Resistance rates for efavirenz, nevirapine and rilpivirine remained above 15% (efavirenz: 17.3%-16.6%, nevirapine: 16.9%-15.4% and rilpivirine: 17.6%-16.1%). This reflects significant cross-resistance between these three NNRTIs. By contrast, resistance rates were lower for etravirine (7.8%-6.0%) and doravirine (4.9%-4.6%), probably due to differences in their resistance profiles and higher genetic barriers to resistance.

Conclusions: The NNRTI class of antiretroviral drugs remains widely used. Changes in the usage of drugs from this class have not altered the ecology of NNRTI resistance in antiretroviral drug-treated PLWHIV with virological failure during the studied period.