Background
Doravirine (DOR) is licensed in patients living with HIV (PWH) harboring no prior resistance to any NNRTIs. We aimed to evaluate in real life the efficacy of DOR-containing regimen in PWH with prior NNRTIs virological failure and selected NNRTI resistance-associated mutations (RAMs).
Methods
This observational single center study included all PWH who have switched to a DOR-containing regimen (two-drug [2-DR] or three-drug regimen [3-DR]) between 30-09-2019 and 01-05-2022, with an HIV-1 RNA ≤50 cp/mL at the time of switch and the presence of past NNRTI-RAMs identified on cumulated RNA and/or DNA genotypes interpreted using the latest ANRS and Stanford algorithms. Main outcome was the proportion of participants with virologic failure at week 48 and week 96. Secondary outcomes evaluated the rate of viral suppression, the rate of transient virologic blip, RAMs in case of virologic failure, the occurrence of side effects and the rate of DOR-containing regimen discontinuation.
Results
A total of 102 patients was analyzed, 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), and they had been on ART for 22 years (IQR 14-26). Median viral suppression duration was 7 years (IQR 1-11), and the median CD4 T cell count/mm3 was 544 (IQR 352-753). Most PWH were infected with non-B subtype virus (51%).
Of the patients analyzed, 25 of 102 (25%) had documented historical RAMs to DOR, with 9 of these 25 cases (36%) showing possible resistance and 16 cases (64%) showing major resistance to this molecule (Table 1). This resistance profile consisted mainly (21/23) 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 virologic failure occurred neither at week 48 (0/87, 0%) nor 96 (0/86, 0%). All 86 patients maintained virologic success either in DOR-3-DR or 2-DR.
Conclusions
Our study provides the first large real-world data on the use of DOR-containing regimens with up to 96 weeks of follow-up. NNRTIs drugs are often compromised by cross-resistance within the class, but with the introduction of DOR, which offers protection even in the presence of some resistant variants in the past, there is still hope for the use of this molecule as an option in salvage regimens for patients with a history of specific NNRTIs-RAMS, provided they have been virologically suppressed for a long time.