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Chemokine analogues show suitable stability for development as microbicides

Landay, Alan
Gichinga, Carolyne
Lederman, Michael M.
Flyckt, Rebecca
Starks, David
Le Gal, Francois
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Published in Journal of acquired immune deficiency syndromes. 2008, vol. 49, no. 5, p. 472-476
Abstract New prevention strategies are urgently needed to slow the spread of the HIV/AIDS pandemic, and in the absence of an effective vaccine, there is hope that "microbicides"-HIV inhibitors applied to mucosal surfaces before sexual intercourse-may be able to make an impact. Because developing countries are at the center of the epidemic, affordability and stability during storage are key criteria for candidate microbicides. Furthermore, because formulation strategies that provide long-duration protection after a single dose may enhance acceptability and compliance, stability in the vaginal environment and in the presence of semen should also be considered. PSC-RANTES, a human chemokine analog, has shown promise as a candidate microbicide, but because it contains nonnatural structures that necessitate chemical synthesis steps, it is not suitable for production at a feasible cost and scale for general distribution in developing countries. We have recently developed 2 new fully recombinant chemokine analogs, 5P12-RANTES and 6P4-RANTES, which show equivalent anti-HIV activity to PSC-RANTES. In this study, we tested the stability of these molecules under conditions related to use as microbicides. Our results suggest that stability issues will not present a major obstacle to the further development of these promising molecules as microbicides.
Keywords Anti-HIV Agents/*chemistry/*pharmacologyChemokine CCL5/chemistry/*pharmacologyChemokines, CC/chemistry/*pharmacologyDose-Response Relationship, DrugDrug StabilityFemaleHeLa CellsHot TemperatureHumansHydrogen-Ion ConcentrationMaleSemen/chemistryVagina/chemistry
PMID: 18989226
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Research group HIV (835)
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CERINI, Fabrice et al. Chemokine analogues show suitable stability for development as microbicides. In: Journal of acquired immune deficiency syndromes, 2008, vol. 49, n° 5, p. 472-476. doi: 10.1097/QAI.0b013e31818c953f https://archive-ouverte.unige.ch/unige:19120

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Deposited on : 2012-03-27

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