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 IC 50 values for two polyanionic carbosilane dendrimers, G2-STE16 and G3-S16. 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 IC 50 increase between 1- and 7-fold in the presence of amyloid fibrils. In peripheral blood mononuclear cells (PBMC), IC 50 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.
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