SHIVA

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SHIVA “Selection and development of microbicides for mucosal use to prevent sexual HIV transmission/acquisition”Type of Project: Integrated Project

Duration: March 2004 – February 2009

Total EU grant: € 3.994.000,00

Section grant: € 848.442,00

Role: Coordinator

Abstract
The main objective of this 5 years IP was the development, up to clinical Phase I, of a specific HIV microbicide for the prevention of sexual transmission/acquisition of HIV, based on the interruption of viral replication at the mucosal level.
Some Members of a new class of non-nucleoside reverse transcriptase inhibitors (NNRTIs), the DABOs, proved capable of irreversibly knocking out HIV-1 replication. This property correlates with their ability to tightly bind to the HIV-1 reverse transcriptase. The lead compound of this series of tight binding NNRTIs is MC1220.
The organization of this Project comprised 3 discovery chemistry teams, combined with a 3D modelling team, who investigated other compounds for back-up and combination purposes.
The global preclinical and pharmaceutical workflow was organized to permit very rapid access to formulation screening and challenge efficacy models in the macaque in two centres (one in Europe and one in Africa).
Finally, the clinical Phase I trial should have involved HIV medical teams highly engaged in the development of clinical trial and treatment networks in Africa.
The work programme was organized in: i) the research engine for the validation of the concept of MC1220 as a microbicide in in vitro assays and for the design / synthesis optimization of DABOs and new uracil-based NNRTIs; ii) pharmaceutical and preclinical development of the candidate lead compound; iii) formulation screening and challenge efficacy model for proof of principle in a validate primate model for vaginal RT-SHIV challenge; iv) studies and tasks directly aimed at conducting Phase I tolerability studies in women.
Eleven Partners, from academy to industry, contributed to the Project & focused on the respect of timing and achievement of expected objectives, as well as on the diffusion of scientific results and economical benefits to achieve all scientific and regulatory requirements to go to Phase II clinical trial programmes within, for example, EDCTP or Alliance for Microbicide.