ArticleThe Journal of infectious diseases2020
Once-Weekly Oral Dosing of MK-8591 Protects Male Rhesus Macaques From Intrarectal Challenge With SHIV109CP3.
Article in The Journal of infectious diseases, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed.
- Two phase 1 studies of safety, tolerability, and pharmacokinetics of an EFdA prodrug (BRII-732) in healthy adult participants.Antimicrobial agents and chemotherapy · 2025Trial
- Effect of HIV Self-Testing on PrEP Adherence Among Gender-Diverse Sex Workers in Uganda: A Randomized Trial.Journal of acquired immune deficiency syndromes (1999) · 2022Trial
- Safety and pharmacokinetics of islatravir subdermal implant for HIV-1 pre-exposure prophylaxis: a randomized, placebo-controlled phase 1 trial.Nature medicine · 2021Trial
- Safety, tolerability, and pharmacokinetics of single- and multiple-dose administration of islatravir (MK-8591) in adults without HIV.Clinical and translational science · 2021Trial
- Next-Generation HIV-1 Therapeutics in Co-Endemic Settings.Biomedicines · 2026Review
- Review
- HIV pre-exposure prophylaxis programmatic preferences among people who inject drugs: findings from a discrete choice experiment.Addiction science & clinical practice · 2024Article
- Preventing perinatal HIV acquisition; current gaps and future perspectives.Current opinion in HIV and AIDS · 2024Review
- Defining blood hematology reference values in female pig-tailed macaques (Macaca nemestrina) using the Isolation Forest algorithm.Journal of medical primatology · 2024Article
- Weekly Oral Tenofovir Alafenamide Protects Macaques from Vaginal and Rectal Simian HIV Infection.Pharmaceutics · 2024Article
- Pharmacokinetic Modeling to Guide Preclinical Development of an Islatravir-Eluting Reservoir-Style Biodegradable Implant for Long-Acting HIV PrEP.Pharmaceutics · 2024Article
- Pharmacokinetic Study of Islatravir and Etonogestrel Implants in Macaques.Pharmaceutics · 2023Article
- Next generation 3D-printed intravaginal ring for prevention of HIV and unintended pregnancy.Biomaterials · 2023Article
- Long-acting lenacapavir acts as an effective preexposure prophylaxis in a rectal SHIV challenge macaque model.The Journal of clinical investigation · 2023Article
- Long-acting HIV pre-exposure prophylaxis (PrEP) approaches: recent advances, emerging technologies, and development challenges.Expert opinion on drug delivery · 2022Review
- The predictive value of macaque models of preexposure prophylaxis for HIV prevention.Current opinion in HIV and AIDS · 2022Review
- Approved HIV reverse transcriptase inhibitors in the past decade.Acta pharmaceutica Sinica. B · 2022Review
- Intracellular islatravir pharmacology differs between species in an in vitro model: implications for preclinical study design.The Journal of antimicrobial chemotherapy · 2022Article
- Antiretroviral drug exposure in urethral and glans surface sampling of the penis.The Journal of antimicrobial chemotherapy · 2021Article
- Multipurpose Prevention Technologies: Oral, Parenteral, and Vaginal Dosage Forms for Prevention of HIV/STIs and Unplanned Pregnancy.Polymers · 2021Review
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Authors and funding
13 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundMK-8591 (4'-ethynyl-2-fluoro-2'-deoxyadenosine [EFdA]) is a novel reverse transcriptase-translocation inhibitor.
methodsWe 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.
resultsControl 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.
conclusionsThese data support MK-8591's potential as a preexposure prophylaxis agent.
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Registered trials
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