G2-S16 sulfonate dendrimer as new therapy for treatment failure in HIV-1 entry inhibitors

Nanomedicine (Lond). 2019 May;14(9):1095-1107. doi: 10.2217/nnm-2018-0364. Epub 2019 May 8.

Abstract

Aim: Polyanionic carbosilane dendrimers have been shown to be safe and block human immunodeficiency virus type 1 (HIV-1) infection in a multifunctional manner. The aim of this study is to evaluate the appearance of HIV-1 resistance mutations after treatment with polyanionic carbosilane dendrimers. Materials & methods: A resistance mutation assay was performed on MT2 cells, viral quantity was measured by ELISA HIVp24gag and titration was carried out on TZM.bl. Next generation sequencing for HIV-1 Env was performed on G1-S4 or G2-S16 dendrimers supernatants. Results: Data showed the appearance of mutation resistance to G1-S4 treatment, inducing three significant mutations. G2-S16 did not generate any mutations and, furthermore, inhibited G1-S4-resistant viruses. Conclusion: G1-S4 treatment generates significant mutations in HIV-1NL4.3. G2-S16 does not generate resistance-associated mutation, suggesting that G2-S16 is safe as a HIV-entry inhibitor.

Keywords: G1-S4; G2-S16; HIV-1; dendrimer; mutation; resistance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-HIV Agents / pharmacology*
  • Cell Line
  • Dendrimers / chemistry
  • Dendrimers / pharmacology*
  • Drug Resistance, Viral
  • HIV Envelope Protein gp120 / genetics
  • HIV-1 / drug effects*
  • HIV-1 / physiology
  • Humans
  • Mutation
  • Silanes / chemistry
  • Silanes / pharmacology*
  • Treatment Failure
  • Virus Internalization / drug effects

Substances

  • Anti-HIV Agents
  • Dendrimers
  • HIV Envelope Protein gp120
  • Silanes
  • carbosilane