Evaluating the use of non-nucleoside reverse transcriptase inhibitors in carrageenan-based microbicides
Presentation at XVII International AIDS Conference, Mexico City, 3-8 August
Fernandez-Romero,Jose A.; Maguire,Robin A.; Zydowsky,Thomas M.; Mawson,Paul; Chudolij,Anne; Begay,Othell; Ford,Brian E.; Phillips,David M.
Publication date: 2008
Non-nucleoside reverse transcriptase inhibitors have emerged as strong candidates in the microbicide field. Nevertheless, an extensive characterization has to be done before selecting the best candidate, including high affinity for the reverse transcriptase, selectivity, resistance profile, virucidal activity, low systemic absorption, and stability.
Four different non-nucleoside reverse transcriptase inhibitors (MV007662-1, MV008216-1, MV012403-1, and MV2531-1) developed by Medivir were selected to study their potential use in carrageenan-based microbicides. Cytotoxicity was assessed using the XTT assay. Antiviral and virucidal activities as well as combination effects with carrageenan were analyzed using the MAGI assay. Additionally, we studied the resistance profile and the antiviral activity against multidrug-resistant HIV-1 primary isolates.
All compounds showed a selective antiviral activity with EC50 values between 0.4 and 2 ng/mL and an additive effect when combined with carrageenan. MV2531-1 had the strongest virucidal activity. The development of resistance against MV2531-1 was considerably delayed compared to the other compounds, and the ability of MV2531-1 to block the multidrug-resistant HIV-1 strains was significantly stronger than any of the other compounds tested.
Our results suggest MV2531-1 may be a promising microbicide candidate.
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