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Updated: Aug 16, 2025
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Rapid Screening of HIV Reverse Transcriptase and Integrase Inhibitors
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Different Pathways Conferring Integrase Strand-Transfer Inhibitors Resistance
Clémence Richetta1, Nhat Quang Tu1, Olivier Delelis1
1Laboratoire de Biologie et Pharmacologie Appliquée, ENS-Paris-Saclay, CNRS UMR 8113, Université Paris-Saclay, 91190 Gif-sur-Yvette, France.
Viruses
|December 23, 2022
Summary
Integrase Strand Transfer Inhibitors (INSTIs) combat HIV but develop resistance. This review details HIV resistance mutations and unintegrated viral DNA, aiding new drug development.
Area of Science:
- Virology
- Drug Resistance
- Antiviral Therapy
Background:
- Integrase Strand Transfer Inhibitors (INSTIs) are crucial for human immunodeficiency virus (HIV) treatment.
- First-generation INSTIs (e.g., Raltegravir, Elvitegravir) face viral resistance and cross-resistance.
- Second-generation INSTIs (e.g., Dolutegravir, Cabotegravir, Bictegravir) were developed to overcome resistance but are also subject to it.
Purpose of the Study:
- To review the mechanism of action of INSTIs.
- To summarize and evaluate common HIV resistance mutations against INSTIs.
- To discuss the role of unintegrated viral DNA in INSTI resistance.
Main Methods:
- Literature review of INSTI mechanisms and resistance.
- Analysis of substitution and insertion mutations conferring resistance.
- Evaluation of the contribution of unintegrated viral DNA to resistance.
Main Results:
- INSTIs are effective HIV therapies but face evolving viral resistance.
- Both first and second-generation INSTIs can be circumvented by HIV mutations.
- Unintegrated viral DNA represents a novel mechanism for INSTI resistance.
Conclusions:
- Understanding HIV resistance mechanisms to INSTIs is critical.
- Further research into resistance pathways, including unintegrated DNA, is needed.
- This knowledge can guide the development of next-generation INSTIs.
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