BACKGROUND: MK-8591 (4'-ethynyl-2-fluoro-2'-deoxyadenosine [EFdA]) is a novel reverse transcriptase-translocation inhibitor. METHODS: We assessed MK-8591 as preexposure prophylaxis in the rhesus macaque model of intrarectal challenge with simian/human immunodeficiency virus (SHIV). In study 1, 8 rhesus macaques received 3.9 mg/kg of MK-8591 orally on day 0 and once weekly for the next 14 weeks. Eight controls were treated with vehicle. All rhesus macaques were challenged with SHIV109CP3 on day 6 and weekly for up to 12 challenges or until infection was confirmed. The dose of MK-8591 was reduced to 1.3 and 0.43 mg/kg/week in study 2 and further to 0.1 and 0.025 mg/kg/week in study 3. In studies 2 and 3, each dose was given up to 6 times once weekly, and animals were challenged 4 times once weekly with SHIV109CP3. RESULTS: Control macaques were infected after a median of 1 challenge (range, 1-4 challenges). All treated animals in studies 1 and 2 were protected, consistent with a 41.5-fold lower risk of infection (P < .0001, by the log-rank test). In study 3, at a 0.1-mg/kg dose, 2 rhesus macaques became infected, consistent with a 7.2-fold lower risk of infection (P = .0003, by the log-rank test). The 0.025-mg/kg dose offered no protection. CONCLUSIONS: These data support MK-8591's potential as a preexposure prophylaxis agent.
BACKGROUND:MK-8591 (4'-ethynyl-2-fluoro-2'-deoxyadenosine [EFdA]) is a novel reverse transcriptase-translocation inhibitor. METHODS: We assessed MK-8591 as preexposure prophylaxis in the rhesus macaque model of intrarectal challenge with simian/human immunodeficiency virus (SHIV). In study 1, 8 rhesus macaques received 3.9 mg/kg of MK-8591 orally on day 0 and once weekly for the next 14 weeks. Eight controls were treated with vehicle. All rhesus macaques were challenged with SHIV109CP3 on day 6 and weekly for up to 12 challenges or until infection was confirmed. The dose of MK-8591 was reduced to 1.3 and 0.43 mg/kg/week in study 2 and further to 0.1 and 0.025 mg/kg/week in study 3. In studies 2 and 3, each dose was given up to 6 times once weekly, and animals were challenged 4 times once weekly with SHIV109CP3. RESULTS: Control macaques were infected after a median of 1 challenge (range, 1-4 challenges). All treated animals in studies 1 and 2 were protected, consistent with a 41.5-fold lower risk of infection (P < .0001, by the log-rank test). In study 3, at a 0.1-mg/kg dose, 2 rhesus macaques became infected, consistent with a 7.2-fold lower risk of infection (P = .0003, by the log-rank test). The 0.025-mg/kg dose offered no protection. CONCLUSIONS: These data support MK-8591's potential as a preexposure prophylaxis agent.
Authors: Enzo Tramontano; Bart Tarbet; Jessica R Spengler; Katherine Seley-Radtke; Chris Meier; Robert Jordan; Zlatko Janeba; Brian Gowen; Brian Gentry; José A Esté; Mike Bray; Graciela Andrei; Luis M Schang Journal: Antiviral Res Date: 2019-07-11 Impact factor: 5.970
Authors: Craig Sykes; Brian Van Horne; Justin Jones; Angela D M Kashuba; Gregory Gatto; Ariane Van Der Straten; Leah Johnson; Mackenzie L Cottrell Journal: J Antimicrob Chemother Date: 2022-03-31 Impact factor: 5.758
Authors: Jonathan T Su; Solange M Simpson; Samuel Sung; Ewa Bryndza Tfaily; Ronald Veazey; Mark Marzinke; Jiang Qiu; David Watrous; Lakmini Widanapathirana; Elizabeth Pearson; M Melissa Peet; Dipu Karunakaran; Brooke Grasperge; Georgina Dobek; Charlette M Cain; Thomas Hope; Patrick F Kiser Journal: Antimicrob Agents Chemother Date: 2020-02-21 Impact factor: 5.191
Authors: Randolph P Matthews; Wendy Ankrom; Evan Friedman; Deanne Jackson Rudd; Yang Liu; Robin Mogg; Deborah Panebianco; Inge De Lepeleire; Magdalena Petkova; Jay A Grobler; Selwyn Aubrey Stoch; Marian Iwamoto Journal: Clin Transl Sci Date: 2021-08-31 Impact factor: 4.689
Authors: Andrew Mujugira; Agnes Nakyanzi; Maria S Nabaggala; Timothy R Muwonge; Timothy Ssebuliba; Monica Bagaya; Olivia Nampewo; Oliver Sapiri; Kikulwe R Nyanzi; Felix Bambia; Rogers Nsubuga; David M Serwadda; Norma C Ware; Jared M Baeten; Jessica E Haberer Journal: J Acquir Immune Defic Syndr Date: 2022-04-01 Impact factor: 3.771