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

Córdoba, Enrique Vacasa,b,d; Arnáiz, Eduardoc,d; De La Mata, Francisco J.c,d; Gómez, Rafaelc,d; Leal, Manuele; Pion, Marjoriea,b,d; Muñoz-Fernández, Ma Ángelesa,b,d

AIDS:
doi: 10.1097/QAD.0b013e328361fa4a
Basic Science: Concise Communication
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.

Author Information

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.

Correspondence to Ma Ángeles Muñoz-Fernández, Laboratorio InmunoBiología Molecular, Hospital General Universitario Gregorio Marañón. CIBER BBN, C/Dr Esquerdo 46, 28007 Madrid, Spain. Tel: +915 868 565; fax: +915 868 018; e-mail: mmunoz.hgugm@gmail.com/mmunoz.hgugm@salud.madrid.org

Received 24 January, 2013

Revised 10 March, 2013

Accepted 4 April, 2013

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© 2013 Lippincott Williams & Wilkins, Inc.