www.hivandhepatitis.com

New NRTI Microbicide Looks Promising in Lab

A novel vaginal microbicide gel containing the reverse transcriptase inhibitor IQP-0528 demonstrated good antiviral activity and safety in laboratory studies.

Researchers are working on several biomedical HIV prevention strategies, ranging from vaccines to pre-exposure prophylaxis (PrEP). Microbicides containing antiretroviral drugs have received considerable attention, especially given the promising results from the CAPRISA trial testing a tenofovir-based gel in women in South Africa.

As described in the April 2011 issue of Antimicrobial Agents and Chemotherapy, Alamelu Mahalingam from the University of Utah and colleagues evaluated the safety and antiviral efficacy of a pyrimidinedione compound known as IQP-0528 being developed by ImQuest BioSciences. This agent was selected for further development due to its stability under physiologically relevant conditions, a wide therapeutic window, and antiviral activity in the nanomolar range.

The researchers developed 2 vaginal gels formulations containing IQP-0528, one using 3.0% hydroxyethyl cellulose, the other 0.65% Carbopol polymer. The properties of these gels were evaluated in laboratory studies using cells lines and human cervical tissue samples.

Results

• The gels demonstrated physical and chemical stability for 3 months.
• The 3.0% HEC gel had the best potential bioavailability and was selected for safety and activity evaluations.
• In vitro and ex vivo safety evaluations of 3.0% HEC gel containing 0.25% IQP-0528 showed "no significant loss in cell viability or significant inflammatory response."
• An in vitro HIV-1 entry inhibition assay showed that this formulation had a 50% effective concentration of 0.14 mcg/mL in culture media.
• In ex vivo cervical tissue, the gel demonstrated "complete protection against HIV infection."

Based on these findings, the researchers concluded, "these results are encouraging and warrant further evaluation of IQP-0528 gel formulations in in vivo models, as well as the development of alternative formulations for the delivery of IQP-0528 as a microbicide."

"[T]his formulation is expected to provide complete protection against infection with no significant toxicity or irritation to vaginal tissue," they added in their discussion. They estimated that the cost of the gel could be as low as 30 cents per dose, making it affordable in resource-limited settings.

Investigator affiliations: Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, UT; Department of Bioengineering, University of Utah, Salt Lake City, UT; ImQuest BioSciences, Inc., Frederick, MD; Department of Obstetrics, Gynecology, and Reproductive Sciences, University of Pittsburgh, Magee-Womens Research Institute, Pittsburgh, PA.

5/6/11

Source

A Mahalingam, AP Simmons, SR Ugaonkar, et al. Vaginal microbicide gel for delivery of IQP-0528, a pyrimidinedione analog with a dual mechanism of action against HIV-1. Antimicrobial Agents and Chemotherapy 55(4):1650-1660 (abstract). April 2011.