M48U1 and Tenofovir combination synergistically inhibits HIV infection in activated PBMCs and human cervicovaginal histocultures

Giuseppina Musumeci (1) , Isabella Bon (1) , David Lembo (2) , Valeria Cagno , Maria Carla Re (1) , Caterina Signoretto (3) , Erica Diani (3) , Lucia Lopalco (4) , Claudia Pastori , Loïc M Martin (5, 6) , Gilles Ponchel (7) , Davide Gibellini (3) , Kawthar Bouchemal (8)

1 UNIBO - Alma Mater Studiorum Università di Bologna = University of Bologna
2 UNITO - Università degli studi di Torino = University of Turin
3 UNIVR - Università degli studi di Verona = University of Verona
4 Division of Immunology, Infectious Diseases and Transplantation
5 SIMoS - Service d'Ingénierie Moléculaire pour la Santé (ex SIMOPRO)
6 MTS - Médicaments et Technologies pour la Santé
7 PCPB - Physico-chimie, pharmacotechnie, biopharmacie
8 IGPS - Institut Galien Paris-Sud

Microbicides are considered a promising strategy for preventing human immunodeficiency virus (HIV-1) transmission and disease. In this report, we first analyzed the antiviral activity of the miniCD4 M48U1 peptide formulated in hydroxyethylcellulose (HEC) hydrogel in activated peripheral blood mononuclear cells (PBMCs) infected with R5- and X4–tropic HIV-1 strains. The results demonstrate that M48U1 prevented infection by several HIV-1 strains including laboratory strains, and HIV-1 subtype B and C strains isolated from the activated PBMCs of patients. M48U1 also inhibited infection by two HIV-1 transmitted/founder infectious molecular clones (pREJO.c/2864 and pTHRO.c/2626). In addition, M48U1 was administered in association with tenofovir, and these two antiretroviral drugs synergistically inhibited HIV-1 infection. In the next series of experiments, we tested M48U1 alone or in combination with tenofovir in HEC hydrogel with an organ-like structure mimicking human cervicovaginal tissue. We demonstrated a strong antiviral effect in absence of significant tissue toxicity. Together, these results indicate that co-treatment with M48U1 plus tenofovir is an effective antiviral strategy that may be used as a new topical microbicide to prevent HIV-1 transmission.

Domaines: Chimie thérapeutique; Gynécologie et obstétrique; Maladies infectieuses; Virologie; Pharmacologie

Giuseppina Musumeci, Isabella Bon, David Lembo, Valeria Cagno, Maria Carla Re, et al.. M48U1 and Tenofovir combination synergistically inhibits HIV infection in activated PBMCs and human cervicovaginal histocultures. Scientific Reports, 2017, 7 (1), ⟨10.1038/srep41018⟩. ⟨hal-02530919⟩