No virological failure in patients living with HIV with past NNRTI resistance-associated mutations switched to doravirine-containing regimens

Doravirine is licensed in patients living with HIV (PWH) harbouring no prior resistance to any NNRTIs. We aimed to evaluate in real life the efficacy of doravirine with prior NNRTI virological failure and NNRTI resistance-associated mutations (RAMs). This observational study included PWH switched to a doravirine-containing regimen between 30 September 2019 and 1 May 2022, with an HIV-1 RNA of ≤50 copies/mL and past NNRTI-RAMs. The main outcome was the proportion of participants with virological failure at Week 48 and Week 96. Secondary outcomes evaluated the rate of viral suppression and transient virological blip, RAMs in the case of virological failure and side effects. A total of 102 patients were analysed, mostly men (63%), with a median age of 59 years (IQR 51-63). The median time since HIV-1 diagnosis was 26 years (IQR 16-31), on ART for 22 years (IQR 14-26) and virally suppressed for 7 years (IQR 1-11).Of the patients analysed, 25/102 (25%) had documented historical RAMs to doravirine, 9/25 (36%) showing possible resistance and 16/25 (64%) showing major resistance. The resistance profile primarily (21/23) consisted of the K103N, Y181C and/or G190A/E reverse transcriptase substitutions. Median time since the last detection of NNRTI-RAMs was 12 years (5-17). Over 2 years follow-up, no virological failure occurred, neither at Week 48 (0/87; 0%) nor Week 96 (0/86; 0%). This is the first real-world study to provide new insight about the use of doravirine-containing regimens as a treatment in long-term suppressed patients whose viruses harboured specific NNRTI-RAMs in their history.