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Recent Advances in the Development of Integrase Inhibitors for HIV Treatment

  • HIV Pathogenesis and Treatment (AL Landay and NS Utay, Section Editors)
  • Published:
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Abstract

Purpose of the Review

The complex multistep life cycle of HIV allows it to proliferate within the host and integrate its genome in to the host chromosomal DNA. This provirus can remain dormant for an indefinite period. The process of integration, governed by integrase (IN), is highly conserved across the Retroviridae family. Hence, targeting integration is not only expected to block HIV replication but may also reveal new therapeutic strategies to treat HIV as well as other retrovirus infections.

Recent Findings

HIV integrase (IN) has gained attention as the most promising therapeutic target as there are no equivalent homologues of IN that has been discovered in humans. Although current nano-formulated long-acting IN inhibitors have demonstrated the phenomenal ability to block HIV integration and replication with extraordinary half-life, they also have certain limitations.

Summary

In this review, we have summarized the current literature on clinically established IN inhibitors, their mechanism of action, the advantages and disadvantages associated with their therapeutic application, and finally current HIV cure strategies using these inhibitors.

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Acknowledgements

We thank Robin Taylor for editorial help.

Funding

This work is partially supported by National Institute of Allergy and Infectious Diseases Grant R01 AI129745. This work was also supported by the JC Bose fellowship to DM and DST-INSPIRE Fellowship to JT.

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  1. Jay Trivedi

    Present address: Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, USA

Authors and Affiliations

  1. National Centre for Cell Science, Pune University Campus, Pune, Maharashtra, India

    Jay Trivedi & Debashis Mitra

  2. Centre for DNA Fingerprinting and Diagnostics, Uppal Telangana state, Hyderabad, India

    Debashis Mitra

  3. Drug Discovery Research Centre, Translational Health Science and Technology Institute, NCR Biotech Science Cluster, 3rd Milestone, Faridabad, Haryana, India

    Dinesh Mahajan

  4. Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, USA

    Russell J. Jaffe, Arpan Acharya & Siddappa N. Byrareddy

  5. Department of Genetics, Cell Biology and Anatomy, University of Nebraska Medical Center, Omaha, NE, USA

    Siddappa N. Byrareddy

  6. Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA

    Siddappa N. Byrareddy

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Trivedi, J., Mahajan, D., Jaffe, R.J. et al. Recent Advances in the Development of Integrase Inhibitors for HIV Treatment. Curr HIV/AIDS Rep 17, 63–75 (2020). https://doi.org/10.1007/s11904-019-00480-3

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