Resistance to novel drug classes

Anne Genevieve Marcelin, Francesca Ceccherini-Silberstein, Carlo Federico Perno, Vincent Calvez

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

PURPOSE OF REVIEW: Understanding the mechanisms that underlie resistance development to novel drugs is essential to a better clinical management of resistant viruses and to prevent further resistance development and spread. RECENT FINDINGS: Integrase inhibitors and CCR5 antagonists are the more recent antiretroviral classes developed. The HIV-1 integrase, responsible for the chromosomal integration of the newly synthesized double-stranded viral DNA into the host genomic DNA, represents a new and important target; and two integrase inhibitors (INIs), raltegravir and elvitegravir, have been shown promising results in clinical trials. Viral entry is also an attractive step for the development of new drugs against HIV variants resistant to current antiretroviral drugs, and two CCR5 antagonists have been designed to inhibit HIV-1 binding to R5 co-receptor and are under clinical investigation. SUMMARY: Drug resistance to INIs occurs through the selection of mutations within HIV integrase. The kinetic of selection seems rapid and one mutation alone is able to confer resistance to integrase inhibitor, suggesting that this class of drug has a low genetic barrier. Two ways could explain the failure of the CCR5 antagonist class: a rapid outgrowth of pre-existing archived X4 virus or the selection of a resistance to CCR5 antagonists through amino acid changes in V3 loop.

Original languageEnglish
Pages (from-to)531-537
Number of pages7
JournalCurrent Opinion in HIV and AIDS
Volume4
Issue number6
DOIs
Publication statusPublished - Nov 2009

Fingerprint

Integrase Inhibitors
Pharmaceutical Preparations
HIV Integrase
Essential Drugs
Viruses
Mutation
DNA
Viral DNA
Drug Resistance
HIV-1
Clinical Trials
HIV
Amino Acids

Keywords

  • Antiretrovirals
  • CCR5
  • Integrase
  • New classes

ASJC Scopus subject areas

  • Hematology
  • Oncology(nursing)
  • Immunology
  • Infectious Diseases
  • Virology
  • Oncology

Cite this

Marcelin, A. G., Ceccherini-Silberstein, F., Perno, C. F., & Calvez, V. (2009). Resistance to novel drug classes. Current Opinion in HIV and AIDS, 4(6), 531-537. https://doi.org/10.1097/COH.0b013e328331d4b1

Resistance to novel drug classes. / Marcelin, Anne Genevieve; Ceccherini-Silberstein, Francesca; Perno, Carlo Federico; Calvez, Vincent.

In: Current Opinion in HIV and AIDS, Vol. 4, No. 6, 11.2009, p. 531-537.

Research output: Contribution to journalArticle

Marcelin, AG, Ceccherini-Silberstein, F, Perno, CF & Calvez, V 2009, 'Resistance to novel drug classes', Current Opinion in HIV and AIDS, vol. 4, no. 6, pp. 531-537. https://doi.org/10.1097/COH.0b013e328331d4b1
Marcelin, Anne Genevieve ; Ceccherini-Silberstein, Francesca ; Perno, Carlo Federico ; Calvez, Vincent. / Resistance to novel drug classes. In: Current Opinion in HIV and AIDS. 2009 ; Vol. 4, No. 6. pp. 531-537.
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