ArticleThe Journal of antimicrobial chemotherapy2021
In vitro cross-resistance to doravirine in a panel of HIV-1 clones harbouring multiple NNRTI resistance mutations.
Article in The Journal of antimicrobial chemotherapy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 20 citations in OpenAlex.
- Deep Contrastive Learning for High-Throughput Prediction of Drug Resistance Mutations from Sequences.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Efficacy, safety, and anti-inflammatory properties of the switch to a doravirine-based regimen among antiretroviral-experienced elderly people living with HIV-1: the DORAGE cohort.Antimicrobial agents and chemotherapy · 2025Article
- Identification of a novel small-molecule inhibitor of the HIV-1 reverse transcriptase activity with a non-nucleoside mode of action.Virology journal · 2025Article
- Article
- Potential role of doravirine for the treatment of HIV-1-infected persons with transmitted drug resistance.AIDS research and therapy · 2023Article
- Doravirine-associated resistance mutations in antiretroviral therapy naïve and experienced adults with HIV-1 subtype C infection in Botswana.Journal of global antimicrobial resistance · 2022Article
- Deep sequencing of HIV-1 reveals extensive subtype variation and drug resistance after failure of first-line antiretroviral regimens in Nigeria.The Journal of antimicrobial chemotherapy · 2022Article
- High Prevalence of Doravirine Resistance in HIV-1-Infected Patients with Virological Failure to an NNRTI-Based Single-Tablet Regimen.Infection and drug resistance · 2022Article
- Impact of HIV-1 Resistance-Associated Mutations on Susceptibility to Doravirine: Analysis of Real-World Clinical Isolates.Antimicrobial agents and chemotherapy · 2021Article
- Review
- Is there a role for doravirine in African HIV treatment programmes? A large observational resistance study in South Africa.Journal of the International AIDS Society · 2021Observational
- Liver Damage During Treatment with Reverse-Transcriptase Inhibitors in HIV Patients.Current health sciences journalReview
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
objectivesDoravirine is a recently licensed HIV-1 NNRTI with improved efficacy, pharmacokinetics and safety profile compared with efavirenz and limited cross-resistance with rilpivirine and etravirine. In this in vitro study, cross-resistance to doravirine was analysed in a representative panel of NNRTI-resistant clones.
methodsIn vitro phenotypic susceptibility to doravirine was assessed in 10 clinically derived infectious clones with intermediate- to high-level resistance to rilpivirine, etravirine, efavirenz and nevirapine, and in NL4-3 site-directed mutants harbouring K103N, Y181C, M230L or K103N/Y181C NNRTI mutations.
resultsAlthough none of the infectious clones harboured any of the major doravirine resistance-associated mutations (RAMs) included in the IAS-USA reference list, doravirine fold change (FC) values were comparable to or higher than those calculated for other NNRTIs, particularly etravirine and rilpivirine. As expected, single NNRTI mutations K103N and Y181C did not impair doravirine susceptibility (FC 1.4 and 1.8, respectively), while reduced activity was observed with the single M230L or double K103N/Y181C mutations (FC 7.6 and 4.9, respectively). Median FC values increased significantly with increasing numbers of NNRTI RAMs (P = 0.005) and were >10 in 4/4 and 1/4 clones harbouring four and three NNRTI RAMs, respectively. FC values correlated well with predicted susceptibility as inferred by Stanford HIV Drug Resistance Database (HIVdb) and ANRS algorithms (both P < 0.001).
conclusionsSubstantial cross-resistance to doravirine was detected in NNRTI-resistant viruses harbouring complex mutational patterns, even in the absence of major IAS-USA doravirine RAMs. Therefore, based on the simple IAS-USA reference list, doravirine resistance may be underestimated in viruses harbouring multiple NNRTI mutations.
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