01 Set M48U1 and Tenofovir combination synergistically inhibits HIV-1 infection in activated PBMCs and human cervicovaginal histocultures
Microbicides are currently considered a promising strategy for preventing human immunodeficiency virus (HIV-1) transmission and disease. In this report, we first analysed the antiviral activity of miniCD4 M48U1 peptide formulated in hydroxyethylcellulose hydrogel (HEC) on activated peripheral blood mononuclear cells (PBMCs) infected by R5 and X4–tropic HIV-1 strains. The results demonstrated that M48U1 prevented infection by several HIV-1 virus strains including laboratory strains, and HIV-1 subtype B and C strains isolated from patients in activated peripheral blood mononuclear cells. M48U1 has also inhibited two HIV-1 transmitted/founder infectious molecular clones (pREJO.c/2864 and pTHRO.c/2626). In addition, M48U1 was tested in association with tenofovir, and these two antiretroviral drugs synergistically inhibited HIV-1. In the next series of experiments, we tested M48U1 alone or in combination with tenofovir in HEC hydrogel with an organ-like structure mimicking the human cervicovaginal tissue and we demonstrated a strong antiviral effect without any induction of significant tissue toxicity. Together, these results indicate that co-treatment with M48U1 plus tenofovir can exert an effective antiviral activity, and this association may represent a new topical microbicide to prevent HIV-1 transmission.