HIV-1 drug resistance profile in patients with inefficient antiretroviral therapy containing elsulfavirine

The aim. To determine the HIV-1 drug resistance profile in patients with virological failure to elsulfavirine-containing antiretroviral therapy in a real-world clinical setting.

Materials and methods. The study group consisted of HIV-1 nucleotide sequences (pol gene fragments encoding protease and part of reverse transcriptase) from 179 HIV-infected patients with virological failure of elsulfavirine-containing antiretroviral therapy and who had not previously received other non-nucleoside reverse transcriptase inhibitors. Resistance mutations were identified and HIV-1 drug resistance was determined using the HIVdb database (v. 9.8).

Results and discussion. HIV-1 mutations associated with viral resistance to non-nucleoside reverse transcriptase inhibitors were detected in 88.3% of patients with virological failure of elsulfavirine-containing antiretroviral therapy. Previously described HIV-1 resistance profiles to elsulfavirine were detected in only 5.1% of the studied patients. A total of 29 mutations were detected, the most common being V106I (46.9%), E138K (38.5%), H221Y (34.6%), E138Q (20.7%), F227C (12.3%), Y181C (11.7%), K101E (11.2%), and E138A (10.6%). A total of 87 different HIV-1 mutation patterns were detected, with combinations of two or more mutations predominating (70.9%). The main patterns detected included combinations of mutations V106I/M, E138K/Q/G, and H221Y±K101E, F227C, G190S, and M230L. High levels of HIV-1 resistance in the studied patients were most frequently detected to rilpivirine (60.9%), which limits its successful use in patients taking elsulfavirine, and least frequently to doravirine (22.9%) and etravirine (9.5%), which allows them to be considered as options for switching.

Conclusion. This study identified the main mutations associated with elsulfavirine-containing therapy failure, potential pathways for the development of HIV-1 resistance to the drug, and HIV-1 cross-drug resistance to other drugs in class. However, most of the patterns identified in this study have not been previously described, indicating the need to update data on the HIV1 resistance profile to elsulfavirine.

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