Navigation path

SHIVA


HIV/AIDS

Selection and Development of Microbicides for Mucosal Use to Prevent Sexual HIV Transmission/Acquisition
Framework programme:
6
Call:
1
Project number:
LSHP-CT-2004-503162
EC contribution:
€ 3,800,000
Duration:
48 months
Type:
IP
Starting date:
1 March 2004

Keywords: Microbicides; HIV; DABOs; MC 1220; NNRTIs; women; clinical trial

Summary:

The main objective of the SHIVA project is to develop MC 1220 up to clinical phase I. This is a novel non-nucleoside inhibitor of the HIV-1 reverse transcriptase, capable of irreversibly knocking out the HIV replication in vitro. The project integrates all the required skills, from chemistry (University of Southern Demark, Odense; Università La Sapienza, Roma; Idenix, Montpellier), to virology (IRD, Montpellier; University of Cagliari), enzymology (CNRS-AMFB, Marseille), pharmaceutical technology (University of Patras), pharmaco-toxicology (Università di Milano; Idenix, Montpellier); primate models (DPZ, Göttingen; CIRMF, Franceville), and clinical research (Hôpital de la Salpétrière, Paris). During the four years of the project, various basic and applied research topics will be addressed.

  • Proving the efficacy of MC 1220 in preventing HIV-1 multiplication (reverse transcription and integration) in dendritic cells, macrophages and lymphocytes, i.e. in the primary targets of the virus following its penetration into genital mucosal surfaces. A key goal will be to prove that MC 1220 is effective against the wide variety of HIV-1 belonging to the different groups and subtypes circulating in developing countries.
  • Finding the most proper formulation to deliver and accumulate MC 1220 inside the above target cells in the mucosa.
  • Proving the efficacy of MC 1220 in protecting the genital mucosae of rhesus monkeys from challenging with a human/simian immunodeficiency virus chimera.
  • Starting phase I tolerability clinical trials in HIV positive and negative women.

Background:

The SHIVA project is part of a novel strategy to fight the transmission of HIV by means of products, known as microbicides. Designed for mucosal use, they would provide a convenient and readily available method of self-protection against HIV. Some members of a new class of non-nucleoside reverse transcriptase inhibitors (NNRTIs), the the Dihydro-alkoxy-benzyl-oxopyrimidines (DABOs), proved to be capable of irreversibly knocking out the HIV-1 replication. This property was found to correlate with their ability to bind tightly to the HIV-1 non-nucleoside binding site (NNBS) of reverse transcriptase (RT). The lead compound of this series of ‘tight binding NNRTIs’ is MC1220.

[+] Read More