G2-S16 sulfonate dendrimer as new therapy for treatment failure in HIV-1 entry inhibitors

Abstract

Aim: Polyanionic carbosilane dendrimers have been shown to be safe and block human immunodeficiency virus type 1 (HIV-1) infection in a multifunctional manner. The aim of this study is to evaluate the appearance of HIV-1 resistance mutations after treatment with polyanionic carbosilane dendrimers. Materials & methods: A resistance mutation assay was performed on MT2 cells, viral quantity was measured by ELISA HIVp24^gag and titration was carried out on TZM.bl. Next generation sequencing for HIV-1 Env was performed on G1-S4 or G2-S16 dendrimers supernatants. Results: Data showed the appearance of mutation resistance to G1-S4 treatment, inducing three significant mutations. G2-S16 did not generate any mutations and, furthermore, inhibited G1-S4-resistant viruses. Conclusion: G1-S4 treatment generates significant mutations in HIV-1_NL4.3. G2-S16 does not generate resistance-associated mutation, suggesting that G2-S16 is safe as a HIV-entry inhibitor.

Keywords: G1-S4; G2-S16; HIV-1; dendrimer; mutation; resistance.