New monthly pill shows potential as pre-exposure prophylaxis HIV drug candidate, reveals research

Researchers from Merck engaged in a lead optimization campaign to develop a novel nucleoside reverse transcriptase translocation inhibitor (NRTTI). NRTTIs are a new class of anti-HIV drugs that have shown potential for long-acting prophylaxis. They inhibit viral replication by more than one mechanism, including blocking translocation of reverse transcriptase on the growing viral DNA chain.

Using a known NRTTI, islatravir, as a starting point, researchers used several medicinal chemistry strategies to modify the structure and optimize it using both in vitro and in vivo assays. The lead compound, dubbed MK-8527, showed robust antiviral activity in vitro, and pharmacokinetics in animal studies demonstrated that it may be suitable as a long-acting oral therapy. Studies in humans are underway to assess the safety and tolerability of MK-8527 as a once-monthly oral pill in volunteers at low likelihood of HIV exposure, and at least one completed clinical study shows promising results.

Reference:

Izzat T. Raheem ,Vinay Girijavallabhan,Kerry L. Fillgrove,Shih Lin Goh,Carolyn Bahnck-Teets,Qian Huang,Fangbiao Li,Bang-Lin Wan,Gregory T. O’Donnell,Jonathan B. Patteson,Maria E. Cilento,Amrith Bennet, MK-8527 is a novel inhibitor of HIV-1 reverse transcriptase translocation with potential for extended-duration dosing, PLOS Biology, https://doi.org/10.1371/journal.pbio.3003308.