ArticleAntimicrobial agents and chemotherapy2013
Effect of mutations at position E138 in HIV-1 reverse transcriptase and their interactions with the M184I mutation on defining patterns of resistance to nonnucleoside reverse transcriptase inhibitors rilpivirine and etravirine.
Article in Antimicrobial agents and chemotherapy, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 71 citations in OpenAlex.
- HIV-1 drug resistance among individuals who seroconverted in the ASPIRE dapivirine ring trial.Journal of the International AIDS Society · 2021Trial
- Antiretroviral activity and safety of once-daily etravirine in treatment-naive HIV-infected adults: 48-week results.Antiviral therapy · 2016Trial
- Notable transmitted HIV drug resistance among people who inject drugs in Pakistan.The Journal of antimicrobial chemotherapy · 2026Article
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- One Year of Long-Acting Cabotegravir and Rilpivirine in People With Human Immunodeficiency Virus and Long Exposure to Antiretroviral Therapy: Data From the SCohoLART Study.Open forum infectious diseases · 2024Article
- Structure-based design and optimization lead to the identification of novel dihydrothiopyrano[3,2-Acta pharmaceutica Sinica. B · 2024Article
- Article
- HIV-1 Drug Resistance among Treatment-Naïve Patients in Russia: Analysis of the National Database, 2006-2022.Viruses · 2023Article
- Molecular Epidemiology and Trends in HIV-1 Transmitted Drug Resistance in Mozambique 1999-2018.Viruses · 2022Article
- Cryo-EM structures of wild-type and E138K/M184I mutant HIV-1 RT/DNA complexed with inhibitors doravirine and rilpivirine.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- How could HIV-1 drug resistance impact preexposure prophylaxis for HIV prevention?Current opinion in HIV and AIDS · 2022Review
- Prevalence and Evolution of Transmitted Human Immunodeficiency Virus Drug Resistance in Belgium Between 2013 and 2019.Open forum infectious diseases · 2022Article
- Analytical Assessment of the Vela Diagnostics NGS Assay for HIV Genotyping and Resistance Testing: The Apulian Experience.International journal of molecular sciences · 2022Article
- Pre-existing singleton E138A mutations in the reverse transcriptase gene do not affect the efficacy of first-line antiretroviral therapy regimens using rilpivirine in human immunodeficiency virus-infected patients.Clinical case reports · 2022Article
- Limited nucleotide changes of HIV-1 subtype B Rev response element in China affect overall Rev-RRE activity and viral replication.Frontiers in microbiology · 2022Article
- Avoiding Drug Resistance in HIV Reverse Transcriptase.Chemical reviews · 2021Review
- High nonnucleoside reverse transcriptase inhibitor resistance levels in HIV-1-infected Zambian mother-infant pairs.AIDS (London, England) · 2020Article
- Development of non-nucleoside reverse transcriptase inhibitors (NNRTIs): our past twenty years.Acta pharmaceutica Sinica. B · 2020Review
- Natural presence of the V179D and K103R/V179D mutations associated with resistance to nonnucleoside reverse transcriptase inhibitors in HIV-1 CRF65_cpx strains.BMC infectious diseases · 2020Article
- Discordance between Etravirine Phenotype and Genotype-Based Predicted Phenotype for Subtype C HIV-1 from First-Line Antiretroviral Therapy Failures in South Africa.Antimicrobial agents and chemotherapy · 2020Article
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
Impacts of mutations at position E138 (A/G/K/Q/R/V) alone or in combination with M184I in HIV-1 reverse transcriptase (RT) were investigated. We also determined why E138K is the most prevalent nonnucleoside reverse transcriptase inhibitor mutation in patients failing rilpivirine (RPV) therapy. Recombinant RT enzymes and viruses containing each of the above-mentioned mutations were generated, and drug susceptibility was assayed. Each of the E138A/G/K/Q/R mutations, alone or in combination with M184I, resulted in decreased susceptibility to RPV and etravirine (ETR). The maximum decrease in susceptibility to RPV was observed for E138/R/Q/G by both recombinant RT assay and cell-based assays. E138Q/R-containing enzymes and viruses also showed the most marked decrease in susceptibility to ETR by both assays. The addition of M184I to the E138 mutations did not significantly change the levels of diminution in drug susceptibility. These findings indicate that E138R caused the highest level of loss of susceptibility to both RPV and ETR, and, accordingly, E138R should be recognized as an ETR resistance-associated mutation. The E138K/Q/R mutations can compensate for M184I in regard to both enzymatic fitness and viral replication capacity. The favored emergence of E138K over other mutations at position E138, together with M184I, is not due to an advantage in either the level of drug resistance or viral replication capacity but may reflect the fact that E138R and E138Q require two distinct mutations to occur, one of which is a disfavorable G-to-C mutation, whereas E138K requires only a single favorable G-to-A hypermutation. Of course, other factors may also affect the concept of barrier to resistance.
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