ArticleAntimicrobial agents and chemotherapy2011
In Vitro antiretroviral properties of S/GSK1349572, a next-generation HIV integrase inhibitor.
Article in Antimicrobial agents and chemotherapy, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 176 papers, 2 of them syntheses 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
176 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Dolutegravir(DTG, S/GSK1349572) combined with other ARTs is superior to RAL- or EFV-based regimens for treatment of HIV-1 infection: a meta-analysis of randomized controlled trials.AIDS research and therapy · 2016Pooled it
- Clinical practice guideline for the management of chronic kidney disease in patients infected with HIV: 2014 update by the HIV Medicine Association of the Infectious Diseases Society of America.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2014Guideline
- Trial
- Twice-Daily Dosing of Dolutegravir in Infants on Rifampicin Treatment: A Pharmacokinetic Substudy of the EMPIRICAL Trial.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2024Trial
- Impact of Integrase Sequences from HIV-1 Subtypes A6/A1 on theAntimicrobial agents and chemotherapy · 2022Trial
- 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
- Comparing timelines and evidence available to support new TB, HIV, and HCV drug approvals: The same, only different.PloS one · 2022Trial
- Simplified dolutegravir dosing for children with HIV weighing 20 kg or more: pharmacokinetic and safety substudies of the multicentre, randomised ODYSSEY trial.The lancet. HIV · 2020Trial
- Bioequivalence and Food Effect Assessment of 2 Fixed-Dose Combination Formulations of Dolutegravir and Lamivudine.Clinical pharmacology in drug development · 2020Trial
- ING116070: a study of the pharmacokinetics and antiviral activity of dolutegravir in cerebrospinal fluid in HIV-1-infected, antiretroviral therapy-naive subjects.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2014Trial
- Dolutegravir in antiretroviral-experienced patients with raltegravir- and/or elvitegravir-resistant HIV-1: 24-week results of the phase III VIKING-3 study.The Journal of infectious diseases · 2014Trial
- Dolutegravir in antiretroviral-naive adults with HIV-1: 96-week results from a randomized dose-ranging study.AIDS (London, England) · 2013Trial
- Safety and efficacy of dolutegravir in treatment-experienced subjects with raltegravir-resistant HIV type 1 infection: 24-week results of the VIKING Study.The Journal of infectious diseases · 2013Trial
- Effect of food on the pharmacokinetics of the integrase inhibitor dolutegravir.Antimicrobial agents and chemotherapy · 2012Trial
- 1,4-Dihydroxy-1,8-napthyridinone (DHN) analogs as HIV-1 reverse transcriptase-associated RNase H inhibitors.Bioorganic chemistry · 2026Article
- Simulation-Based Predictions to Support the Development of a Pediatric Fixed-Dose Combination of Dolutegravir/Emtricitabine/Tenofovir Alafenamide Fumarate.Clinical pharmacokinetics · 2026Review
- First-line dolutegravir/lamivudine penetrates lymph nodes and reduces HIV reservoirs comparably to triple therapy.Research square · 2026Article
- Article
- Review
- Contemporary antiretroviral pharmacology in the male genital tract: implications for HIV treatment and prevention.Antimicrobial agents and chemotherapy · 2026Review
116 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
18 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
S/GSK1349572 is a next-generation HIV integrase (IN) inhibitor designed to deliver potent antiviral activity with a low-milligram once-daily dose requiring no pharmacokinetic (PK) booster. In addition, S/GSK1349572 demonstrates activity against clinically relevant IN mutant viruses and has potential for a high genetic barrier to resistance. S/GSK1349572 is a two-metal-binding HIV integrase strand transfer inhibitor whose mechanism of action was established through in vitro integrase enzyme assays, resistance passage experiments, activity against viral strains resistant to other classes of anti-HIV agents, and mechanistic cellular assays. In a variety of cellular antiviral assays, S/GSK1349572 inhibited HIV replication with low-nanomolar or subnanomolar potency and with a selectivity index of 9,400. The protein-adjusted half-maximal effective concentration (PA-EC(50)) extrapolated to 100% human serum was 38 nM. When virus was passaged in the presence of S/GSK1349572, highly resistant mutants were not selected, but mutations that effected a low fold change (FC) in the EC(50) (up to 4.1 fold) were identified in the vicinity of the integrase active site. S/GSK1349572 demonstrated activity against site-directed molecular clones containing the raltegravir-resistant signature mutations Y143R, Q148K, N155H, and G140S/Q148H (FCs, 1.4, 1.1, 1.2, and 2.6, respectively), while these mutants led to a high FC in the EC(50) of raltegravir (11- to >130-fold). Either additive or synergistic effects were observed when S/GSK1349572 was tested in combination with representative approved antiretroviral agents; no antagonistic effects were seen. These findings demonstrate that S/GSK1349572 would be classified as a next-generation drug in the integrase inhibitor class, with a resistance profile markedly different from that of first-generation integrase inhibitors.
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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.