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Tenofovir CAPRISA 004 1% tenofovir vaginal gel 39% HIV-1 51% HSV-2 “Life is really simple, but we insist on making it complicated.” Confucius Coinfection of human lymphoid tissue ex vivo Recto-sigmoid HIV-1 HSV and other viruses Tenofovir suppresses HSV-2 in the presence of HIV-1 HSV-2G HIV-1LAI.04 Tenofovir 200 μM HIV-1 p24 (10-3/mL) HSV-2G replication (log10 copies/mL) Tenofovir 200 μM + - + + + + - + + + 3 2 1 0 Tenofovir Oral Local Tenofovir Tenofovir-diphosphate IC50 =4.3 µM HIV-1 RT IC50 =1.3 µM HSV DNA polymerase HCV HSV OTHER HIV Tenofovir Acyclovir CONCLUSIONS Tenofovir is a dual-targeted drug that suppresses both HIV-1 and HSV replication. Tenofovir at concentrations generated during oral drug administration that may (or may not) inhibits HIV transmission are substantially lower than those necessary to inhibit herpes-simplex viruses. In general, these findings argue that “marginal” antiviral activities of a variety of existing drugs should be revisited to test for possibly missed antiviral activities since in topical applications these drugs may constitute new microbicides with dual or multiple antiviral properties. Andrea Lisco Christophe Vanpouille, Andrea Introini NICHD, NIH Graciela Andrei, Robert Snoeck, Joost van den Oord, Jan Balzarini Rega Institute Emanuela Balestra, Carlo-Federico Perno University of Roma Tor Vergata, Tomas Cihlar Gilead Sciences, Inc.