Doravirine Associated Resistance Mutations in Antiretroviral Therapy Naïve and Experienced Adults with HIV-1 subtype C Infection in Botswana

Journal of Global Antimicrobial Resistance

Doravirine (DOR), a non-nucleoside reverse transcriptase inhibitor (NNRTI), has an opportunity for use as part of first-line antiretroviral therapy (ART) among people with HIV(PWH). However, there is limited data on the prevalence of DOR-associated drug resistance mutations in PWH in Botswana. The aim of the study is to explore the prevalence of DOR-associated resistance mutations among ART-naïve and ART-experienced PWH in Botswana. The overall prevalence of any DOR-associated resistance mutations was 181/1473 [12.3% (95% CI: 10.7-14.1)]. By ART status, individuals who are experiencing virologic failure (VL>400 copies/mL) on ART have notably high resistance compared to those who have never taken ART. The predicted prevalence of individuals who have high reduced susceptibility of DOR based regimen was 33/1261 [2.6% (95% CI: 1.8-3.7)] among ART-naïve lower than 13/212 [6.1%(95% CI: 3.6-10.8)] among those failing on ART (p<0.01). However, DOR-associated mutations were rare (11.0%) in those who had never used ART, but they were present in 62.7% of Botswana patients who failed NNRTI-based ART. Testing for HIV drug resistance should underpin the use of DOR in PWH who have taken first-generation NNRTIs.

SANTHE is an Africa Health Research Institute (AHRI) flagship programme funded by the Science for Africa Foundation through the DELTAS Africa programme; the Bill & Melinda Gates Foundation; Gilead Sciences Inc.; and the Ragon Institute of Mass General, MIT, and Harvard.