Doravirine resistance is uncommon in people with HIV who have been treated with non-nucleoside reverse transcriptase inhibitors (NNRTI), which confirms a distinguishing resistance pattern with NNRTI, according to research results published in The International Journal of Antimicrobial Agents.

Samples from 6893 NNRTI-experienced patients who underwent genotypic testing for virologic failure from the Antiretroviral Response Cohort Analysis database were included in the study. Of these, 64.2% were previously treated with efavirenz, 54.4% with nevirapine, 6.8% with etravirine, 7.7% with rilpivirine, and 0.7% with delavirdine. Intermediate doravirine resistance was defined as detection of any of V106A/M, Y188C/H, V108I, K103N, and P225H and high-level resistance to detection of Y188L, M230L, G190E, V106A/M plus F227L, V106A/M and L234I.

Of patients treated with NNRTIs, intermediate and high levels of resistance were found in 12.7% and 6.1%, respectively, and the most common doravirine resistance mutation was Y188L. Using multivariable analysis, the detection of high-level resistance was associated with previous efavirenz and etravirine use (odds ratio [OR] 1.52; 95% CI, 1.15-2.02 and OR 1.91; 95% CI, 1.34-2.73, respectively) and the detection of the Y188L mutation (OR 1.76; 95% CI, 1.19-2.58 and OR 1.72; 95% CI, 1.10-2.68, respectively). Rilpivirine use was associated with a lower probability of high-level doravirine resistance (OR 0.39; 95% CI, 0.22-0.71) and was not associated with detection of the Y188L mutation (OR 0.16; 95% CI, 0.05-0.50).

The study investigators noted that, “a low representation of patients treated with [etravirine] and [rilpivirine] and the fact that [doravirine] resistance was defined based on in vitro studies in the absence of a reference mutation list derived from clinical studies,” was a limitation of this study. As a result, the researchers cautioned that, “the full potential of [doravirine] use after NNRTI experience should thus be reappraised along with definition of its resistance profile in vivo.”

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The results, according to the researchers, support potential significant doravirine use even in NNRTI-experienced patients. This is because the prevalence of resistance mutations to doravirine remains low in patients who present with mutations against the NNRTIs currently in use. However, clinical research is still needed to confirm the role of doravirine in vivo because patients with NNRTI-resistant viruses to date have not been included in completed clinical trials.

Reference

Sterrantino G, Borghi V, Callegaro AP, et al. Prevalence of predicted resistance to Doravirine in HIV-1 positive patients after exposure to non-nucleoside reverse transcriptase inhibitors [published online February 12 2019]. Int J Antimicrob Agents. doi:10.1016/j.ijantimicag.2019.02.007