Trial reportAntimicrobial agents and chemotherapy2022
Emergence of Resistance in HIV-1 Integrase with Dolutegravir Treatment in a Pediatric Population from the IMPAACT P1093 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. It is linked to trial NCT01302847 (Phase I/II, Multi-Center, Open-Label Pharmacokinetic, Safety, Tolerability and Antiviral Activity of Dolutegravir, a Novel Integrase Inhibitor, in Combination Regimens in HIV-1 Infected Infants, Children and Adolescents), which is not on this map. Cited by 23 papers.
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.
Phase I/II, Multi-Center, Open-Label Pharmacokinetic, Safety, Tolerability and Antiviral Activity of Dolutegravir, a Novel Integrase Inhibitor, in Combination Regimens in HIV-1 Infected Infants, Children and Adolescents
Who cites it
23 citing papers in PubMed, 32 citations in OpenAlex.
- Once-daily dolutegravir-based antiretroviral therapy in infants and children living with HIV from age 4 weeks: results from the below 14 kg cohort in the randomised ODYSSEY trial.The lancet. HIV · 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
- Review
- Emerging Dolutegravir Resistance Among Children on Antiretroviral Therapy With Virological Failure in Malawi: Results From a 2023 National Cross-Sectional Survey.Journal of the International AIDS Society · 2026Article
- Low Prevalence of Integrase Inhibitor Resistance Following Treatment Failure: A Real-World Analysis from Hunan Province, China.Infection and drug resistance · 2026Article
- Article
- Correlates of virological non-suppression among children and adolescents aged 5-19 years on Dolutegravir-based regimens attending Gulu regional referral hospital, Northern Uganda: a mixed methods cross-sectional study.BMC infectious diseases · 2025Article
- HIV-1 Drug Resistance in Children and Implications for Pediatric Treatment Strategies: A Systematic Review and Meta-analysis.Open forum infectious diseases · 2025Review
- New Therapies and Strategies to Curb HIV Infections with a Focus on Macrophages and Reservoirs.Viruses · 2024Review
- Development and Optimization of Oligonucleotide Ligation Assay (OLA) Probes for Detection of HIV-1 Resistance to Dolutegravir.Viruses · 2024Article
- Prevalence of Emergent Dolutegravir Resistance Mutations in People Living with HIV: A Rapid Scoping Review.Viruses · 2024Article
- Virologic outcomes with tenofovir-lamivudine-dolutegravir in adults failing PI-based second-line ART.Southern African journal of HIV medicine · 2024Article
- Strengthening and enhancing national antiretroviral drug resistance surveillance in Zimbabwe-A country that has reached UNAIDS 95-95-95 amongst adults.Frontiers in public health · 2024Article
- Article
- Advancing HIV Drug Resistance Technologies and Strategies: Insights from South Africa's Experience and Future Directions for Resource-Limited Settings.Diagnostics (Basel, Switzerland) · 2023Review
- 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
- Prevalence of HIV-1 Natural Polymorphisms and Integrase-Resistance-Associated Mutations in African Children.Viruses · 2023Article
- Article
- Breaking the unbreakable: A paediatric case of dolutegravir resistance from KwaZulu-Natal.Southern African journal of HIV medicine · 2023Article
- Comparing albuvirtide plus ritonavir-boosted lopinavir regimen to two nucleotide reverse transcriptase inhibitors plus ritonavir-boosted lopinavir in HIV-infected individuals who failed initial treatment: a retrospective comparative cohort study.Annals of translational medicine · 2022Article
Corrections and comments
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Authors and funding
9 authors at 6 institutions in 1 country.
Funding
Abstract
P1093 is a multicenter, open-label, phase I/II study of pharmacokinetics, safety, and tolerability of dolutegravir plus an optimized background regimen in pediatric participants aged 4 weeks to <18 years with HIV-1. Most participants were highly treatment experienced. We report the mechanisms of emergent integrase strand transfer inhibitor (INSTI) resistance among adolescents and children receiving dolutegravir. Plasma was collected at screening and near protocol-defined virologic failure (PDVF) for population-level and, for some samples, clonal-level integrase genotyping, phenotyping, and replication capacity. HIV-1 RNA was assessed in all available plasma samples. Phylogenetic analysis of clonal integrase sequences and homology modeling of HIV-1 intasome complexes containing resistance-associated substitutions were performed. Treatment-emergent INSTI resistance was detected in 8 participants who met PDVF criteria. The rare INSTI resistance-associated substitution G118R or R263K developed in 6 participants. The on-study secondary integrase substitution E157Q or L74I was observed in 2 participants. G118R reduced dolutegravir susceptibility and integrase replication capacity more than R263K and demonstrated greater reduction in susceptibility and integrase replication capacity when present with specific secondary integrase substitutions, including L74M, T66I, and E138E/K. Continuing evolution after R263K acquisition led to reduced dolutegravir susceptibility and integrase replication capacity. Structural examination revealed potential mechanisms for G118R- and R263K-mediated INSTI resistance. G118R and R263K INSTI resistance substitutions, which are distinct to second-generation INSTIs, were detected in adolescents and children with prior virologic failure who received dolutegravir. This study provides additional molecular and structural characterization of integrase to aid in the understanding of INSTI resistance mechanisms in antiretroviral-experienced populations. (This study has been registered at ClinicalTrials.gov under identifier NCT01302847.).
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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.