In:
The Journal of Infectious Diseases, Oxford University Press (OUP), Vol. 221, No. 9 ( 2020-04-07), p. 1398-1406
Abstract:
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 & lt; .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.
Type of Medium:
Online Resource
ISSN:
0022-1899
,
1537-6613
DOI:
10.1093/infdis/jiz271
Language:
English
Publisher:
Oxford University Press (OUP)
Publication Date:
2020
detail.hit.zdb_id:
1473843-0
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