Synergistic activity of carbosilane dendrimers in combination with maraviroc against HIV in vitro

AIDS. 2013 Aug 24;27(13):2053-8. doi: 10.1097/QAD.0b013e328361fa4a.

Abstract

Objective: Dendrimers have been shown as effective and safe anti-HIV compounds with great potential as topical microbicides. Currently, the most advanced microbicides are based on antiretrovirals. However, nowadays none of them has shown any success in clinical trials.

Design: Antiviral activity and combinatorial profile of different combinations between CCR5 co-receptor antagonist, maraviroc (MRV), and polyanionic carbosilane dendrimers against HIV-1 strains were evaluated.

Methods: Cellular in-vitro models were used to evaluate the antiviral action of combinations of carbosilane dendrimers/MRV against CCR5 and dual tropic viral strains in TZM.bl cells and peripheral blood mononuclear cells. Combinatorial analysis was performed using Calcusyn software.

Results: In the majority of combinations tested, dendrimers showed synergistic profile with MRV against CCR5 and dual tropic HIV-1.

Conclusion: The evaluated two-drug combinations increase their antiviral potency supporting further clinical investigations to develop combinatorial formulated topical microbicides to fight against the worldwide HIV spread.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-HIV Agents / pharmacology*
  • Cyclohexanes / pharmacology*
  • Dendrimers / pharmacology*
  • Drug Synergism*
  • HIV-1 / drug effects*
  • HeLa Cells
  • Humans
  • Maraviroc
  • Microbial Sensitivity Tests
  • Silanes / pharmacology*
  • Triazoles / pharmacology*

Substances

  • Anti-HIV Agents
  • Cyclohexanes
  • Dendrimers
  • Silanes
  • Triazoles
  • carbosilane
  • Maraviroc