ArticleAntimicrobial agents and chemotherapy2023
The G118R plus R263K Combination of Integrase Mutations Associated with Dolutegravir-Based Treatment Failure Reduces HIV-1 Replicative Capacity and Integration.
Article in Antimicrobial agents and chemotherapy, 2023. 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, 23 citations in OpenAlex.
- A Real-Time Urine Tenofovir Assay Improves Drug Adherence Among People With HIV With Prior Virologic Failure in a Randomized Controlled Trial.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2025Trial
- Review
- Cooperation between HIV-1 integrase natural polymorphism K156N and 3'PPT mutations in dolutegravir monotherapy failure.The Journal of antimicrobial chemotherapy · 2026Article
- HIV Dolutegravir resistance and multiclass failure in Mozambique: findings from a real-world cohort.BMC infectious diseases · 2025Observational
- Single-cell delineation of strain-specific HIV-1 Vif activities using dual reporter sensor cells and live cell imaging.Journal of virology · 2025Article
- Computational and Population-Based HLA Permissiveness to HIV Drug Resistance-Associated Mutations.Pathogens (Basel, Switzerland) · 2025Article
- Novel Dolutegravir and Lenacapavir Resistance Patterns in Human Immunodeficiency Virus Type 2 Infection: A Case Report.Open forum infectious diseases · 2025Article
- Emergence of Acquired Dolutegravir Resistance in Treatment-experienced People With HIV in Lesotho.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2024Article
- HIV drug resistance to integrase inhibitors in low- and middle-income countries.Nature medicine · 2024Article
- Review
- Article
- 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
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Human immunodeficiency virus (HIV) treatment with antiretroviral regimens containing integrase strand transfer inhibitors such as dolutegravir (DTG) and bictegravir (BIC) offers high levels of protection against the development of drug resistance mutations. Despite this, resistance to DTG and BIC can occur through the development of the R263K integrase substitution. Failure with DTG has also been associated with the emergence of the G118R substitution. G118R and R263K are usually found separately but have been reported together in highly treatment-experienced persons who experienced treatment failure with DTG. We used cell-free strand transfer and DNA binding assays and cell-based infectivity, replicative capacity, and resistance assays to characterize the G118R plus R263K combination of integrase mutations. R263K reduced DTG and BIC susceptibility ~2-fold, in agreement with our previous work. Single-cycle infectivity assays showed that G118R and G118R plus R263K conferred ~10-fold resistance to DTG. G118R alone conferred low levels of resistance to BIC (3.9-fold). However, the G118R plus R263K combination conferred high levels of resistance to BIC (33.7-fold), likely precluding the use of BIC after DTG failure with the G118R plus R263K combination. DNA binding, viral infectivity, and replicative capacity of the double mutant were further impaired, compared to single mutants. We propose that impaired fitness helps to explain the scarcity of the G118R plus R263K combination of integrase substitutions in clinical settings and that immunodeficiency likely contributes to its development.
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