ArticleThe Journal of antimicrobial chemotherapy2016
Development of a G118R mutation in HIV-1 integrase following a switch to dolutegravir monotherapy leading to cross-resistance to integrase inhibitors.
Article in The Journal of antimicrobial chemotherapy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers, 2 of them syntheses that pooled it.
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Who cites it
45 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- A systematic review of the genetic mechanisms of dolutegravir resistance.The Journal of antimicrobial chemotherapy · 2019Pooled it
- Guideline
- Integrase Inhibitor Resistance Mechanisms and Structural Characteristics in Antiretroviral Therapy-Experienced, Integrase Inhibitor-Naive Adults with HIV-1 Infection Treated with Dolutegravir plus Two Nucleoside Reverse Transcriptase Inhibitors in the DAWNING Study.Antimicrobial agents and chemotherapy · 2022Trial
- Review
- Low Prevalence of Integrase Inhibitor Resistance Following Treatment Failure: A Real-World Analysis from Hunan Province, China.Infection and drug resistance · 2026Article
- Resistance to Dolutegravir in Treatment-experienced Patients in South Africa: A Retrospective Cohort Study.Journal of acquired immune deficiency syndromes (1999) · 2025Article
- Computational and Population-Based HLA Permissiveness to HIV Drug Resistance-Associated Mutations.Pathogens (Basel, Switzerland) · 2025Article
- HIV Drug Resistance Profile in Clients Experiencing Treatment Failure After the Transition to a Dolutegravir-Based First-Line Antiretroviral Treatment Regimen in Mozambique.Pathogens (Basel, Switzerland) · 2025Article
- Optimising HIV drug resistance testing laboratory networks in Kenya: insights from systems engineering modelling.BMJ open · 2024Article
- Article
- HIV drug resistance to integrase inhibitors in low- and middle-income countries.Nature medicine · 2024Article
- HIV-1 drug resistance in people on dolutegravir-based antiretroviral therapy: a collaborative cohort analysis.The lancet. HIV · 2023Article
- Limited emergence of resistance to integrase strand transfer inhibitors (INSTIs) in ART-experienced participants failing dolutegravir-based antiretroviral therapy: a cross-sectional analysis of a Northeast Nigerian cohort.The Journal of antimicrobial chemotherapy · 2023Article
- GRL-142 binds to and impairs HIV-1 integrase nuclear localization signal and potently suppresses highly INSTI-resistant HIV-1 variants.Science advances · 2023Article
- The G118R plus R263K Combination of Integrase Mutations Associated with Dolutegravir-Based Treatment Failure Reduces HIV-1 Replicative Capacity and Integration.Antimicrobial agents and chemotherapy · 2023Article
- Review
- Promising Schiff bases in antiviral drug design and discovery.Medicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents · 2023Review
- Article
- Emergence of the G118R Pan-Integrase Resistance Mutation as a Result of Low Compliance to a Dolutegravir-Based cART.Infectious disease reports · 2022Article
- Pre-Treatment Integrase Inhibitor Resistance and Natural Polymorphisms among HIV-1 Subtype C Infected Patients in Ethiopia.Viruses · 2022Article
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Authors and funding
11 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectivesDolutegravir shows a high barrier to resistance with no previously reported cases of acquired integrase mutations during first-line therapy. In this study, rapid development of the G118R mutation arose following a switch from first-line elvitegravir/cobicistat/tenofovir disoproxil fumarate/emtricitabine to dolutegravir monotherapy. The G118R mutation also arose in a treatment-experienced patient switched to dolutegravir monotherapy. The genetic basis for G118R selection and potential phenotypic outcome was ascertained. PATIENT AND
methodsGenotypic analysis was performed on patients with virological failure (<1000 copies/mL) on dolutegravir-containing regimens. The Los Alamos database was queried for glycine codon 118 polymorphisms. Cell culture selections and phenotypic drug susceptibility assays assessed resistance via the G118R pathway.
resultsWe report on two patients who developed viral failure while on dolutegravir monotherapy. Both patients had been on a current or previous regimen containing integrase inhibitors. Virological failure (<1000 copies/mL) emerged early within 2 months following the dolutegravir switch. The appearance of G118R in these two cases and subtype C and CRF02_AG in vitro selections were related to a rare GGA natural polymorphism at codon 118 (1.5% prevalence), facilitating a GGA to AGA transition. Cell culture selections were used to assess the in vitro progression of the G118R pathway leading to cross-resistance to all integrase inhibitors.
conclusionsAlthough resistance to dolutegravir is typically rare, genetic polymorphisms and monotherapy can facilitate the acquisition of G118R.
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