Prevalence of predicted resistance to doravirine in HIV-1-positive patients after exposure to non-nucleoside reverse transcriptase inhibitors

This study investigated the prevalence of doravirine (DOR) resistance mutations in non-nucleoside reverse transcriptase inhibitor (NNRTI)-experienced patients. DOR resistance was assessed in samples from NNRTI-experienced patients who underwent genotypic testing for virological failure from the Antiretroviral Response Cohort Analysis (ARCA) database. Intermediate DOR resistance was defined as detection of any of V106A/M, Y188C/H, V108I, and K103N+P225H. High-level DOR resistance was defined as detection of any of Y188L, M230L, G190E, V106A/M+F227L, and V106A/M+L234I. Overall, 6893 patients were included in the study: 64.2% had experienced efavirenz (EFV), 54.4% nevirapine (NVP), 6.8% etravirine (ETR), 7.7% rilpivirine (RPV) and 0.7% delavirdine. Among NNRTI-experienced patients, 12.7% and 6.1% of subjects had intermediate and high-level DOR resistance, respectively. The most common DOR resistance mutation was Y188L. In multivariable analysis, previous EFV use (OR = 1.52, 95% CI 1.15-2.02) and ETR use (OR = 1.91, 95% CI 1.34-2.73) were associated with detection of high-level DOR resistance, whilst RPV use was associated with a lower probability of high-level DOR resistance (OR = 0.39, 95% CI 0.22-0.71). Moreover, EFV use (OR = 1.76, 95% CI 1.19-2.58) and ETR use (OR = 1.72, 95% CI 1.10-2.68) were associated with detection of the Y188L mutation, whereas RPV use was not (OR = 0.16, 95% CI 0.05-0.50). In Italy, DOR resistance is uncommon among NNRTI-experienced patients, confirming a distinguishing resistance pattern within NNRTIs. However, previous EFV and ETR experience poses a higher risk of DOR resistance. These results support the use of DOR in NNRTI-experienced patients.