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Tenofovir. CAPRISA 004. 51%. 39%. HSV-2. HIV-1. 1% tenofovir vaginal gel. “Life is really simple, but we insist on making it complicated.” Confucius . Coinfection of human lymphoid tissue ex vivo. HSV and other viruses. Recto-sigmoid. HIV-1. 3. HSV-2 G replication
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CAPRISA 004 51% 39% HSV-2 HIV-1 1% tenofovir vaginal gel
“Life is really simple, but we insist on making it complicated.” Confucius
Coinfection of human lymphoid tissue ex vivo HSV and other viruses Recto-sigmoid HIV-1
3 HSV-2G replication (log10 copies/mL) 2 1 0 HSV-2G HIV-1LAI.04 Tenofovir 200 μM • + + + + • - + + • - + - + untreated tenofovir Tenofovir suppresses HSV-2 in the presence of HIV-1 Tenofovir 200 μM HIV-1 p24 (10-3/mL)
Tenofovir Oral Local
Tenofovir Tenofovir-diphosphate IC50 =4.3 µM IC50 =1.3 µM suppression suppression HIV-1 RT HSV DNA polymerase
Acyclovir HCV HSV OTHER HIV Tenofovir
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 BalzariniRega Institute Emanuela Balestra, Carlo-Federico Perno University of Roma Tor Vergata, Tomas Cihlar Gilead Sciences, Inc.