Triple Combination of Carbosilane Dendrimers, Tenofovir and Maraviroc as Potential Microbicide to Prevent HIV-1 Sexual Transmission

Abstract

The three-drug combination increases their antiviral potency and act synergistically as potential microbicide.

Development of water-soluble polyanionic carbosilane dendrimers as novel and highly potent topical anti-HIV-2 microbicides

“…Similar results have been previously obtained for HIV-1 using a combination of these dendrimers with TFV and/or maraviroc. 25,[70][71][72] G2-NS16/TFV/RAL was the most potent combination regimen against HIV-2 isolates, which is consistent with the higher anti-HIV-2 potency of the G2-NS16 dendrimer when given alone relative to the other dendrimers.…”

“…29,68,69 Therefore, to prevent these problems the ideal HIV microbicide should combine different classes of antiretroviral drugs acting in different targets with compounds that act in a non-specific way. 18 Here, we have shown that dendrimer/TFV/RAL combinations at a fixed 1:1:1 ratio have significant synergistic interactions against the primary R5-and X4-HIV-2 isolates. Similar results have been previously obtained for HIV-1 using a combination of these dendrimers with TFV and/or maraviroc.…”

“…[15][16][17] One of the most promising targets of the HIV cycle is the viral entry/fusion process, which is divided into three steps: (i) attachment of gp120 to CD4, (ii) binding to CCR5 and/or CXCR4, and (iii) fusion of the envelope with the cell membrane and releasing of the viral capsid into the cytoplasm of the host cell. 18 Dendrimers containing functionalized groups at their periphery can bind to their target in a multivalent manner, providing a strategy for the development of potent viral entry inhibitors. Although the antiviral activity and the mode of action of carbosilane dendrimers have been studied against HIV-1, their antiviral activity against HIV-2 is currently unknown.…”

Prevention of vaginal and rectal herpes simplex virus type 2 transmission in mice: mechanism of antiviral action

“…40 We previously demonstrated that G1-S4 and G2-S16 displayed a good safety profile and did not cause histopathological alterations in the vaginal epithelium in BALB/c mice and New Zealand White rabbits. 8,17,31 In particular, we have also demonstrated in female h-BLT mice that transmission of HIV-1 was efficiently blocked by vaginally applied G2-S16.…”

“…Previously, we showed that both dendrimers did not induce vaginal irritation or inflammation in BALB/c mice and they were well tolerated for topical application. 8,17,31 Female BALB/c mice (20±2 g) that were 6-8 weeks old were housed at the CBMSO. Animal studies were conducted and approved by the CBMSO Institutional Animal Care and Use Committee (CEEA-CBMSO, Madrid, Spain).…”