Doravirine-associated resistance mutations in antiretroviral therapy naive and experienced adults with HIV-1 subtype C infection in Botswana

Objectives: There are limited data on the prevalence of doravirine (DOR)-associated drug resistance mu-tations in people with HIV (PWH) in Botswana. This cross-sectional, retrospective study aimed to ex-plore the prevalence of DOR-associated resistance mutations among ART-naive and-experienced PWH in Botswana enrolled in the population-based Botswana Combination Prevention Project (BCPP).Methods: A total of 6078 HIV-1C pol sequences were analysed for DOR-associated resistance mutations using the Stanford HIV drug resistance database, and their levels were predicted according to the Stanford DRM penalty scores and resistance interpretation. Virologic failure was defined as HIV-1 RNA load (VL) > 400 copies/mL.Results: Among 6078 PWH, 5999 (99%) had known ART status, and 4529/5999 (79%) were on ART at time of sampling. The suppression rate among ART-experienced was 4517/4729 (96%). The overall preva-lence of any DOR-associated resistance mutations was 181/1473 (12.3% [95% confidence interval {CI}: 10.7-14.1]); by ART status: 42/212 (19.8% [95% CI: 14.7-25.4]) among ART-failing individuals (VL >= 400 copies/mL) and 139/1261 (11.0% [95% CI: 9.3-12.9]) among ART-naive individuals ( P < 0.01). Intermediate DOR-associated resistance mutations were observed in 106/1261 (7.8% [95% CI: 6.9-10.1]) in ART-naive in-dividuals and 29/212 (13.7% [95% CI: 9.4-8.5]) among ART-experienced participants ( P < 0.01). High-level DOR-associated resistance mutations were observed in 33/1261 (2.6% [95% CI: 1.8-3.7]) among ART-naive and 13/212 (6.1% [95% CI: 3.6-10.8]) among ART-failing PWH ( P < 0.01). PWH failing ART with at least one EFV/NVP-associated resistance mutation had high prevalence 13/67 (19.4%) of high-level DOR-associated resistance mutations.Conclusion: DOR-associated mutations were rare (11.0%) among ART-naive PWH but present in 62.7% of Botswana individuals who failed NNRTI-based ART with at least one EFV/NVP-associated resistance mutation. Testing for HIV drug resistance should underpin the use of DOR in PWH who have taken first -generation NNRTIs.(c) 2022 The Authors. Published by Elsevier Ltd on behalf of International Society for Antimicrobial Chemotherapy. This is an open access article under the CC BY license ( http://creativecommons.org/licenses/by/4.0/ )

Automated summary

This study investigated the prevalence of doravirine-associated drug resistance mutations in HIV patients in Botswana and found that doravirine-associated mutations were rare in treatment-naive patients but more common in those who failed non-nucleoside reverse transcriptase inhibitor (NNRTI) treatment.