Once-Weekly Oral Dosing of MK-8591 Protects Male Rhesus Macaques From Intrarectal Challenge With SHIV109CP3

Area of Science:

• Virology
• Pharmacology
• Infectious Diseases

Background:

• MK-8591, also known as 4'-ethynyl-2-fluoro-2'-deoxyadenosine (EFdA), is a novel reverse transcriptase-translocation inhibitor.
• This compound represents a new class of antiretroviral agents with potential for HIV prevention.

Purpose of the Study:

• To evaluate the efficacy of MK-8591 as a pre-exposure prophylaxis (PrEP) against simian/human immunodeficiency virus (SHIV) infection.
• To determine the protective dose range of MK-8591 in a rhesus macaque model.

Main Methods:

• Rhesus macaques were administered varying oral doses of MK-8591 weekly.
• Animals were subjected to intrarectal challenge with SHIV109CP3 up to 12 times.
• Infection status and risk reduction were compared between treated groups and vehicle controls.

Main Results:

• MK-8591 demonstrated significant protection against SHIV infection in rhesus macaques across multiple studies.
• A dose-dependent protective effect was observed, with higher doses showing complete protection.
• Even a low dose of 0.1 mg/kg/week resulted in a statistically significant 7.2-fold lower risk of infection.

Conclusions:

• MK-8591 is a potent pre-exposure prophylaxis agent with demonstrated efficacy in a relevant animal model.
• The findings support the further development of MK-8591 for human use in HIV prevention strategies.
• MK-8591's effectiveness at low doses suggests a favorable pharmacokinetic profile for PrEP.