Efficacy of carbosilane dendrimers with an antiretroviral combination against HIV-1 in the presence of semen-derived enhancer of viral infection

Amyloid fibrils, which are present in semen, were considered to be a cause of topical vaginal gel ineffectiveness in vivo after microbicides failed as HIV-1 prophylaxis. Therefore, it was necessary to determine whether a dendrimer was suitable for further evaluation in an in vitro model of semen-enhanced viral infection (SEVI). We demonstrated that SEVI in TZM. bl cell cultures increased the infectivity of R5-HIV-1(NL)(AD8), pTHRO. c and pCH058. c isolates, causing higher IC50 values for two polyanionic carbosilane dendrimers, G2-STE16 and G3S16. However, both dendrimers maintained protection rates of 90% at non-toxic concentrations. When dendrimers were combined with Tenofovir/Maraviroc (TDF/MVC), the anti-HIV-1 effect remained at a minimum IC50 increase between 1-and7-fold in the presence of amyloid fibrils. In peripheral blood mononuclear cells (PBMC), IC50 values were slightly influenced by the presence of semen. In brief, dendrimers combined with antiretrovirals showed a synergistic effect. This result plays a crucial role in new microbicide formulations, as it overcomes the negative effects of amyloid fibrils.