title: Synergistic activity of carbosilane dendrimers in combination with maraviroc against HIV in vitro.
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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: aLaboratorio InmunoBiología Molecular, Hospital General Universitario Gregorio Marañón bInstituto de Investigación Sanitaria del Gregorio Marañón cInorganic Chemistry Department, University of Alcalá, Alcalá de Henares dCentro Investigación Biomédica en Red, Bioingeniería, Biomateriales y Nanomedicina; CIBER-BNN, Madrid eLaboratory of Immunovirology, Clinic Unit of Infectious Diseases, Microbiology and Preventive Medicine, Institute of Biomedicine of Seville, IBiS, Virgen del Rocío University Hospital/CSIC/University of Seville, Spain.
authors.forename: Enrique Vacas
authors.initials: EV
authors.lastname: Córdoba
authors.forename: Eduardo
authors.initials: E
authors.lastname: Arnáiz
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: De La Mata
authors.forename: Rafael
authors.initials: R
authors.lastname: Gómez
authors.forename: Manuel
authors.initials: M
authors.lastname: Leal
authors.forename: Marjorie
authors.initials: M
authors.lastname: Pion
authors.forename: Ma Angeles
authors.initials: MA
authors.lastname: Muñoz-Fernández
mesh_terms: D019380:Anti-HIV Agents / Q000494:pharmacology*; D003510:Cyclohexanes / Q000494:pharmacology*; D050091:Dendrimers / Q000494:pharmacology*; D004357:Drug Synergism; D015497:HIV-1 / Q000187:drug effects*; D006367:HeLa Cells; D006801:Humans; D000077592:Maraviroc; D008826:Microbial Sensitivity Tests; D012821:Silanes / Q000494:pharmacology*; D014230:Triazoles / Q000494:pharmacology*
chemical_list: D019380:Anti-HIV Agents; D003510:Cyclohexanes; D050091:Dendrimers; D012821:Silanes; D014230:Triazoles; C504072:carbosilane; D000077592:Maraviroc