ArticleThe Journal of infectious diseases2018
HIV-1 Resistance Dynamics in Patients With Virologic Failure to Dolutegravir Maintenance Monotherapy.
Article in The Journal of infectious diseases, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 51 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
The Dolutegravir Antiretroviral Mono-Therapy for HIV Trial
HIV Drug Resistance Profiles Among Individuals Failing Tenofovir/Lamivudine and Dolutegravir First Line Regimen in Brazil
Who cites it
51 citing papers in PubMed, 1 synthesis or guideline pooled it, 78 citations in OpenAlex.
- A systematic review of the genetic mechanisms of dolutegravir resistance.The Journal of antimicrobial chemotherapy · 2019Pooled it
- Characterizing HIV drug resistance in cases of vertical transmission in the VESTED randomized antiretroviral treatment trial.Journal of acquired immune deficiency syndromes (1999) · 2024Trial
- 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
- Evaluation of the management of pretreatment HIV drug resistance by oligonucleotide ligation assay: a randomised controlled trial.The lancet. HIV · 2020Trial
- Predictors of virological failure in HIV-1-infected patients switching to dolutegravir maintenance monotherapy.HIV medicine · 2019Trial
- The hidden reservoir of INSTI resistance: large scale sequence analysis identifies prevalent Gag NC mutations compromising dolutegravir and cabotegravir efficacy.Science China. Life sciences · 2026Article
- Non-integrase mechanisms for dolutegravir resistance.Retrovirology · 2026Review
- Cooperation between HIV-1 integrase natural polymorphism K156N and 3'PPT mutations in dolutegravir monotherapy failure.The Journal of antimicrobial chemotherapy · 2026Article
- Elucidating the mechanism by which HIV-1 nucleocapsid mutations confer resistance to integrase strand transfer inhibitors.Science advances · 2025Article
- Noncanonical HIV drug resistance mutations: need to close existing gaps.AIDS (London, England) · 2025Review
- Elucidating the Mechanism by Which HIV-1 Nucleocapsid Mutations Confer Resistance to Integrase Strand Transfer Inhibitors.bioRxiv : the preprint server for biology · 2025Article
- Article
- Reverse transcription of HIV-1 2-LTR circle transcripts does frequently cause 3'-polypurine tract mutations implicated in dolutegravir resistance.Journal of virology · 2024Article
- Brief Histories of Retroviral Integration Research and Associated International Conferences.Viruses · 2024Review
- Prevalence of Emergent Dolutegravir Resistance Mutations in People Living with HIV: A Rapid Scoping Review.Viruses · 2024Article
- Epistatic pathways can drive HIV-1 escape from integrase strand transfer inhibitors.Science advances · 2024Article
- Genetic diversity in the partial sequence of the HIV-1 gag gene among people living with multidrug-resistant HIV-1 infection.Revista do Instituto de Medicina Tropical de Sao Paulo · 2024Article
- Article
- Transitioning to Dolutegravir in a Programmatic Setting: Virological Outcomes and Associated Factors Among Treatment-Naive Patients With HIV-1 in the Kilombero and Ulanga Antiretroviral Cohort in Rural Tanzania.Open forum infectious diseases · 2023Article
- HIV-1 3'-Polypurine Tract Mutations Confer Dolutegravir Resistance by Switching to an Integration-Independent Replication Mechanism via 1-LTR Circles.Journal of virology · 2023Article
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Authors and funding
14 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Background: A high genetic barrier to resistance to the integrase strand transfer inhibitor (INSTI) dolutegravir has been reported in vitro and in vivo. We describe the dynamics of INSTI resistance-associated mutations (INSTI-RAMs) and mutations in the 3'-polypurine tract (3'-PPT) in relation to virologic failure (VF) observed in the randomized Dolutegravir as Maintenance Monotherapy for HIV-1 study (DOMONO, NCT02401828). Methods: From 10 patients with VF, plasma samples were collected before the start of cART and during VF, and were used to generate Sanger sequences of integrase, the 5' terminal bases of the 3' long terminal repeat (LTR), and the 3'-PPT. Results: Median human immunodeficiency virus RNA load at VF was 3490 copies/mL (interquartile range 1440-4990 copies/mL). INSTI-RAMs (S230R, R263K, N155H, and E92Q+N155H) were detected in 4 patients, no INSTI-RAMs were detected in 4 patients, and sequencing of the integrase gene was unsuccessful in 2 patients. The time to VF ranged from 4 weeks to 72 weeks. In 1 patient, mutations developed in the highly conserved 3'-PPT. No changes in the terminal bases of the 3'-LTR were observed. Conclusions: The genetic barrier to resistance is too low to justify dolutegravir maintenance monotherapy because single INSTI-RAMs are sufficient to cause VF. The large variation in time to VF suggests that stochastic reactivation of a preexisting provirus containing a single INSTI-RAM is the mechanism for failure. Changes in the 3'-PPT point to a new dolutegravir resistance mechanism in vivo. Clinical Trials Registration: NCT02401828.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.