ArticleClinical infectious diseases : an official publication of the Infectious Diseases Society of America2019
A New Mechanism of Resistance of Human Immunodeficiency Virus Type 2 to Integrase Inhibitors: A 5-Amino-Acid Insertion in the Integrase C-Terminal Domain.
Article in Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.
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16 citing papers in PubMed, 1 synthesis or guideline pooled it, 27 citations in OpenAlex.
- Expanded Spectrum of Antiretroviral-Selected Mutations in Human Immunodeficiency Virus Type 2.The Journal of infectious diseases · 2020Pooled it
- Evolution and emergence of the integrase inhibitor 231 insertion resistance mutation in an HIV-2 strain isolated in central Portugal.Virus genes · 2026Article
- Mortality, loss to follow-up and advanced HIV disease following virologic success in West African HIV-2 patients.PloS one · 2025Article
- Article
- Clinical Outcomes of Integrase Strand Transfer Inhibitors Containing Antiretroviral Therapy in HIV-2: A Narrative Review.Infectious diseases and therapy · 2024Review
- Antiretroviral Treatment of HIV-2 Infection: Available Drugs, Resistance Pathways, and Promising New Compounds.International journal of molecular sciences · 2023Review
- Review
- High Instantaneous Inhibitory Potential of Bictegravir and the New Spiro-β-Lactam BSS-730A for HIV-2 Isolates from RAL-Naïve and RAL-Failing Patients.International journal of molecular sciences · 2022Article
- Spectrum of Activity of Raltegravir and Dolutegravir Against Novel Treatment-Associated Mutations in HIV-2 Integrase: A Phenotypic Analysis Using an Expanded Panel of Site-Directed Mutants.The Journal of infectious diseases · 2022Article
- Human Immunodeficiency Virus Type 2: The Neglected Threat.Pathogens (Basel, Switzerland) · 2021Review
- Review
- Long-term immunological responses to treatment among HIV-2 patients in Côte d'Ivoire.BMC infectious diseases · 2020Article
- Insertion as a Resistance Mechanism Against Integrase Inhibitors in Several Retroviruses.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2019Article
- Management of Virologic Failure and HIV Drug Resistance.Infectious disease clinics of North America · 2019Review
- Comparison of the Antiviral Activity of Bictegravir against HIV-1 and HIV-2 Isolates and Integrase Inhibitor-Resistant HIV-2 Mutants.Antimicrobial agents and chemotherapy · 2019Article
- CROI 2019: advances in antiretroviral therapy.Topics in antiviral medicine · 2019Review
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17 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundIntegrase strand transfer inhibitors (INSTIs) are crucial for the treatment of human immunodeficiency virus (HIV) type 2 infection, due to limited available therapeutic options. Recently, bictegravir has been approved for HIV-1, but no data are currently available for HIV-2.
methodsWe assessed the phenotypic susceptibility of 12 HIV-2 clinical isolates, obtained from 2 antiretroviral-naive and 10 antiretroviral-experienced patients, to 5 INSTIs (bictegravir, cabotegravir, dolutegravir, elvitegravir, and raltegravir) at the virological failure of an INSTI-based regimen. The 50% inhibitory concentrations (IC50s) were determined. Phenotypic inhibitory quotients were determined using trough INSTI plasma concentrations.
resultsWild-type viruses were susceptible to the 5 INSTIs, with IC50s in the nanomolar range. Bictegravir had a lower IC50 than the other INSTIs on those HIV-2 isolates bearing major, resistance-associated mutations (codons 143, 148, and 155). We identified a new resistance profile-a 5-amino-acid insertion at codon 231 of the HIV-2 integrase (231INS)-in 6 patients at the virological failure of a raltegravir-based regimen. Those patients had adequate raltegravir concentrations, but harbored multiresistant viruses with low genotypic susceptibility scores (median = 1.5). This insertion rendered isolates highly resistant to raltegravir and elvitegravir, and moderately resistant to dolutegravir and cabotegravir. Regarding bictegravir, 2 isolates remained susceptible and 2 had a slight increase in IC50 (3- to 5-fold change).
conclusionsOur results confirm the potency of INSTI on HIV-2 clinical isolates with wild-type integrase. In addition, we identified a new resistance pathway, 231INS, selected in antiretroviral-experienced patients with multiresistant HIV-2 viruses. This highlights the need of close follow-up of those patients initiating an INSTI-based regimen.
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