title: Polyanionic carbosilane dendrimer-conjugated antiviral drugs as efficient microbicides: Recent trends and developments in HIV treatment/therapy.
abstract: Polyanionic carbosilane dendrimers (PCDs) are potential candidates for the development of new microbicides for the prevention of HIV transmission. Tenofovir (TFV), which has dual antiviral activity (anti-HIV/HSV-2), and maraviroc (MRV) are the most studied antiretrovirals as microbicides. Here, we introduce developments in the design of innovative dendrimer-based microbicides. We also review and discuss the combination of various PCDs with TFV and/or MRV for their anti-HIV-1 activity and synergistic combinatory potential. Well-defined combinations blocking HIV-1 infection in early steps of HIV-1 replication provide greater efficacy than monotherapy, as reflected by the decrease in concentration and increase in HIV-1 inhibition. These combinations are characterized by lower doses, which minimize toxic side-effects and the emergence of multi-drug resistant mutants. The above facts suggest that the combination of first- and second-generation PCDs with TFV and/or MRV represents a promising candidate microbicide for preventing HIV-1 sexual transmission and simultaneously suppressing HSV-2.
  
  
  BACKGROUND
  HIV infection remains a significant and unresolved problem for humankind, despite the development of combination antiretroviral therapy. It has been found that polyanionic carbosilane dendrimers have efficacy in preventing HIV transmission. In this comprehensive review article, the authors discuss the current status and latest development of the use of dendrimers in combination with other antiretroviral drugs as microbicides, which should stimulate others into further research in the fight against HIV.
authors.affiliation: Laboratorio InmunoBiología Molecular, IISGM, BioBank VIH HGM, CIBER-BBN, Madrid, Spain; Plataforma de Laboratorio, Hospital Gregorio Marañón, IISGM, BioBank VIH HGM, CIBER-BBN, Madrid, Spain.
authors.forename: Daniel
authors.initials: D
authors.lastname: Sepúlveda-Crespo
authors.affiliation: Departamento de Química Inorgánica, Universidad de Alcalá, Campus Universitario, Alcalá de Henares, CIBER-BBN, Madrid, Spain.
authors.forename: Rafael
authors.initials: R
authors.lastname: Gómez
authors.affiliation: Departamento de Química Inorgánica, Universidad de Alcalá, Campus Universitario, Alcalá de Henares, CIBER-BBN, Madrid, Spain.
authors.forename: Francisco Javier
authors.initials: FJ
authors.lastname: De La Mata
authors.affiliation: Plataforma de Laboratorio, Hospital Gregorio Marañón, IISGM, BioBank VIH HGM, CIBER-BBN, Madrid, Spain. Electronic address: joseluis.jimenez@salud.madrid.org.
authors.forename: José Luis
authors.initials: JL
authors.lastname: Jiménez
authors.affiliation: Laboratorio InmunoBiología Molecular, IISGM, BioBank VIH HGM, CIBER-BBN, Madrid, Spain; Plataforma de Laboratorio, Hospital Gregorio Marañón, IISGM, BioBank VIH HGM, CIBER-BBN, Madrid, Spain. Electronic address: mmunoz.hgugm@gmail.com.
authors.forename: M Ángeles
authors.initials: MÁ
authors.lastname: Muñoz-Fernández
mesh_terms: D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D000890:Anti-Infective Agents / Q000008:administration & dosage; D050091:Dendrimers / Q000737:chemistry*; D015497:HIV-1 / Q000187:drug effects / Q000502:physiology; D006801:Humans; D000071228:Polyelectrolytes; D011108:Polymers / Q000737:chemistry*; D012821:Silanes / Q000737:chemistry*; D014779:Virus Replication / Q000187:drug effects
chemical_list: D019380:Anti-HIV Agents; D000890:Anti-Infective Agents; D050091:Dendrimers; D000071228:Polyelectrolytes; D011108:Polymers; D012821:Silanes; C504072:carbosilane
keywords: HIV-1/HSV-2; Maraviroc; Microbicide; Polyanionic carbosilane dendrimers; Tenofovir