Trial reportAntimicrobial agents and chemotherapy2022
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.
Trial report in Antimicrobial agents and chemotherapy, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to trial NCT02227238 (A Phase 3b, Randomized, Open-label Study of the Antiviral Activity and Safety of Dolutegravir Compared to Lopinavir/Ritonavir Both Administered With Dual Nucleoside Reverse Transcriptase Inhibitor Therapy in HIV-1 Infected Adult Subjects With Treatment Failure on First Line Therapy), which is not on this map. Cited by 24 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.
A Phase 3b, Randomized, Open-label Study of the Antiviral Activity and Safety of Dolutegravir Compared to Lopinavir/Ritonavir Both Administered With Dual Nucleoside Reverse Transcriptase Inhibitor Therapy in HIV-1 Infected Adult Subjects With Treatment Failure on First Line Therapy
Who cites it
24 citing papers in PubMed, 1 synthesis or guideline pooled it, 33 citations in OpenAlex.
- Risk of Congenital Anomalies with Dolutegravir-Based Anti-retroviral Regimens: A Systematic Review and Meta-analysis.Clinical drug investigation · 2024Pooled it
- A Randomized Trial to Compare Dolutegravir Plus Boosted Darunavir Versus Recommended Standard of Care Antiretroviral Regimens in People With HIV-1, Whose First-line Non-nucleoside Reverse Transcriptase Inhibitor Therapy Has Failed: Final 96-week Results of the D2EFT Study.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2026Trial
- Phase 1 Evaluation of VH4524184, a Third-Generation Integrase Strand Transfer Inhibitor With an Enhanced Resistance Profile.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2025Trial
- Initial Supplementary Dose of Dolutegravir in Second-Line Antiretroviral Therapy: A Noncomparative, Double-Blind, Randomized Placebo-Controlled Trial.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2023Trial
- Emergence of Resistance in HIV-1 Integrase with Dolutegravir Treatment in a Pediatric Population from the IMPAACT P1093 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
- Synergistic pathogenesis: exploring biofilms, efflux pumps and secretion systems in Acinetobacter baumannii and Staphylococcus aureus.Archives of microbiology · 2025Review
- Longer-term virologic outcomes on tenofovir-lamivudine-dolutegravir in second-line ART.Southern African journal of HIV medicine · 2025Article
- Development and Optimization of Oligonucleotide Ligation Assay (OLA) Probes for Detection of HIV-1 Resistance to Dolutegravir.Viruses · 2024Article
- Article
- Prevalence of Emergent Dolutegravir Resistance Mutations in People Living with HIV: A Rapid Scoping Review.Viruses · 2024Article
- Clinical outcomes with second-line dolutegravir in people with virological failure on first-line non-nucleoside reverse transcriptase inhibitor-based regimens in South Africa: a retrospective cohort study.The Lancet. Global health · 2024Observational
- Low prevalence of archived integrase strand transfer inhibitors resistance associated mutations in Botswana before the roll out of dolutegravir based first line antiretroviral therapy.Frontiers in microbiology · 2024Article
- Virologic outcomes with tenofovir-lamivudine-dolutegravir in adults failing PI-based second-line ART.Southern African journal of HIV medicine · 2024Article
- Viral load suppression and HIV-1 drug resistance mutations in persons with HIV on TLD/TAFED in Zambia.PloS one · 2024Article
- Article
- 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
- Article
- Alloferon and Zanamivir Show Effective Antiviral Activity against Influenza A Virus (H1N1) Infection In Vitro and In Vivo.International journal of molecular sciences · 2022Article
Corrections and comments
- Erratum issued
Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
At week 48 in the phase IIIb DAWNING study, the integrase strand transfer inhibitor (INSTI) dolutegravir plus 2 nucleoside reverse transcriptase inhibitors demonstrated superiority to ritonavir-boosted lopinavir in achieving virologic suppression in adults with HIV-1 who failed first-line therapy. Here, we report emergent HIV-1 drug resistance and mechanistic underpinnings among dolutegravir-treated adults in DAWNING. Population viral genotyping, phenotyping, and clonal analyses were performed on participants meeting confirmed virologic withdrawal (CVW) criteria on dolutegravir-containing regimens. Dolutegravir binding to and structural changes in HIV-1 integrase-DNA complexes with INSTI resistance-associated substitutions were evaluated. Of participants who received dolutegravir through week 48 plus an additional 110 weeks for this assessment, 6 met CVW criteria with treatment-emergent INSTI resistance-associated substitutions and 1 had R263R/K at baseline but not at CVW. All 7 achieved HIV-1 RNA levels of <400 copies/mL (5 achieved <50 copies/mL) before CVW. Treatment-emergent G118R was detected in 5 participants, occurring with ≥2 other integrase substitutions, including R263R/K, in 3 participants and without other integrase substitutions in 2 participants. G118R or R263K increased the rate of dolutegravir dissociation from integrase-DNA complexes versus wild-type but retained prolonged binding. Overall, among treatment-experienced adults who received dolutegravir in DAWNING, 6 of 314 participants developed treatment-emergent INSTI resistance-associated substitutions, with a change in
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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.