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

INTRODUCTION: Our aim was to investigate the prevalence of DOR resistance mutations in NNRTI experienced patients.

METHODS: DOR resistance was assessed in samples from patients NNRTI-experienced who underwent genotypic test for virologic failure from the Antiretroviral Response Cohort Analysis (ARCA) database. Intermediate DOR resistance was defined as detection of any of V106A/M, Y188C/H, V108I, K103N plus P225H. High level resistance to DOR was defined as detection of any of Y188L, M230L, G190E, V106A/M plus F227L, V106A/M plus L234I.

RESULTS: Overall, 6893 patients were included: 64.2% experienced to Efavirenz (EFV), 54.4% to Nevirapine (NVP), 6.8% to Etravirine (ETR), 7.7% to Rilpivirine (RPV) 0.7% to Delavirdine. In patients NNRTI experienced, 12.7% and 6.1% subjects had intermediate and high level DOR resistance, respectively. The most common DOR resistance mutation was Y188L. At multivariable analysis, previous EFV and ETV use were associated with the detection of high level DOR resistance (OR: 1.52, 95% CI:1.15-2.02 and OR: 1.91, 95% CI:1.34-2.73 respectively), while RPV use was associated with a lower probability of high level DOR resistance (OR: 0.39, 0.22-0.71). Moreover, EFV use and ETV use were associated with the detection of Y188L mutation (OR: 1.76, 95% CI: 1.19-2.58 and OR: 1.72, 95% CI: 1.10-2.68 respectively), while RPV use was not (OR: 0.16, 95%CI: 0.05-0.50).

CONCLUSIONS: In Italy, DOR resistance is uncommon among patients experienced to NNRTI, confirming a distinguishing resistance pattern within NNRTI. However, previous EFV and ETV experience poses a higher risk of DOR resistance. These results support the use of DOR in patients with NNRTI experience.