Topical Nonnucleoside Reverse Transcriptase Inhibitor MC 1220 Partially Prevents Vaginal RT-SHIV Infection of Macaques
| Autor: | Tina Schultheiss, Sophia G. Antimisiaris, Richard Storer, Roberta Loddo, Christophe Parsy, Nicole Stolte-Leeb, Ulrike Sauermann, Paolo La Colla, Christiane Stahl-Hennig, Monika Franz, Spyridon Mourtas |
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| Rok vydání: | 2011 |
| Předmět: |
Drug
media_common.quotation_subject Immunology Simian Acquired Immunodeficiency Syndrome Human immunodeficiency virus (HIV) Pyrimidinones Biology medicine.disease_cause Virology Disease Transmission Infectious medicine Animals Volume concentration media_common Recombination Genetic Reverse-transcriptase inhibitor Vaginal microbicide virus diseases Simian immunodeficiency virus Macaca mulatta HIV Reverse Transcriptase Nonhuman primate Reverse transcriptase Fluorobenzenes Administration Intravaginal Treatment Outcome Infectious Diseases Anti-Infective Agents Local Female Simian Immunodeficiency Virus medicine.drug |
| Zdroj: | AIDS Research and Human Retroviruses. 27:933-943 |
| ISSN: | 1931-8405 0889-2229 |
| Popis: | The availability of an effective vaginal microbicide would be a major step toward containment of HIV transmission as well as allowing women self-protection against HIV infection. Here we evaluated the efficacy of vaginal application of the potent nonnucleoside reverse transcriptase inhibitor (NNRTI) MC 1220 against vaginal challenge of macaques with RT-SHIV, a chimeric simian immunodeficiency virus (SIV) containing the reverse transcriptase (RT) gene of HIV-1. Challenge infection of monkeys with RT-SHIV currently represents the only nonhuman primate model available to test the anti-HIV-1 effects of NNRTIs. Two different gel formulations containing different MC 1220 concentrations were evaluated for efficacy in female rhesus macaques exposed to RT-SHIV. Five groups of five animals each were treated with two different gel compositions containing no drug, 0.1% or 0.5% MC 1220, followed by vaginal RT-SHIV challenge 30 min later. One animal in each group treated with the low concentration of MC 1220 as well as one control animal remained uninfected after vaginal challenge. By contrast, three of the animals receiving 0.5% MC 1220 remained uninfected, suggesting a threshold of the drug. Despite being negative for plasma viral RNA and absence of seroconversion, almost all uninfected animals exhibited SIV-specific T cells, either in the periphery or in lymph nodes draining the portal of virus entry. Our results make MC 1220 a promising compound for further development as a topical microbicide and warrant additional testing with improved formulation, long-lasting vaginal delivery systems, or even combinations with other inhibitors. |
| Databáze: | OpenAIRE |
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