Low prevalence of doravirine-associated resistance mutations among polish human immunodeficiency-1 (HIV-1)-infected patients

Introduction: Doravirine (DOR) is a novel non-nucleoside reverse transcriptase inhibitor (NNRTI) that retains activity against common NNRTI resistance mutations. In this study, we aimed to investigate the prevalence of DOR resistance mutations compared with that of resistance mutations for other NNRTIs among HIV-1-infected treatment-experienced and -naive patients from Poland. Methods: Resistance to DOR and other NNRTIs was assessed in two datasets: 1760 antiretroviral treatment-naive HIV-1 patients and 200 treatment-experienced patients. All 1960 sequences were derived from the patients using bulk sequencing. For resistance analyses, Stanford HIV drug resistance database scores were used. Results: Overall, DOR resistance was present in 32 patients (1.62%), of whom 13 (0.74%) were naive and 19 (9.50%) were treatment-experienced. The most common DOR resistance mutations observed among the naive patients were A98G and K101E (0.2% each), and those among cART-experienced patients were L100I (2.0%), K101E, V108I, H221Y, and P225H (1.5% each). Furthermore, among the naive patients, less common resistance to DOR (0.7%) compared with that to nevirapine (NVP) (2.1%; p = 0.0013) and rilpivirine (5.40%; p < 0.0001) was observed. For sequences obtained from treatment-experienced patients, the frequency of resistance to DOR (9.5%) was lower than that for efavirenz (25.5%; p < 0.0001) and NVP (26.0%; p < 0.0001). Conclusions: The frequency of transmitted drug resistance to DOR is low, allowing for effective treatment of anti-retroviral treatment-naive patients and rapid treatment initiation. In cART-experienced patients, this agent remains an attractive NNRTI option with a higher genetic barrier to resistance.