image: HIV Virus Creative artwork featuring colorized 3D prints of HIV virus particles. The virus surface (red) is covered with proteins (dark blue) that enable the virus to enter and infect human cells, and additional proteins (teal spheres) that disguise the virus from the immune system. A colorized transmission micrograph of an H9 T cell (blue) appears in the background. Note: proteins not to scale.
Credit: NIAID, Flickr (CC0, https://creativecommons.org/publicdomain/zero/1.0/)
A new HIV antiretroviral shows promise as a long-acting, oral prophylactic agent, according to a new study by Izzat Raheem, Tracy Diamond and colleagues from Merck & Co., Inc., Rahway, NJ, USA, published August 26th in the open-access journal PLOS Biology.
HIV pre-exposure prophylaxis (PrEP) is a key part of reducing the number of new HIV infections. The most common oral PrEP therapies, consisting of once-daily pills, are highly effective at protecting people from acquiring HIV, but they only work if taken properly. Currently, the only long-acting PrEP therapies require injection by a healthcare provider, which isn’t always feasible for people. Long-acting, oral PrEP therapies could facilitate adherence, provide greater privacy and discretion, reduce concerns about stigma, and improve accessibility for more people to initiate and continue on PrEP, ultimately helping to stem the tide of the nearly 1.3 million new HIV infections globally per year.
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.
In your coverage, please use this URL to provide access to the freely available paper in PLOS Biology: https://plos.io/4l6m2h7
Citation: Raheem IT, Girijavallabhan V, Fillgrove KL, Goh SL, Bahnck-Teets C, Huang Q, et al. (2025) MK-8527 is a novel inhibitor of HIV-1 reverse transcriptase translocation with potential for extended-duration dosing. PLoS Biol 23(8): e3003308. https://doi.org/10.1371/journal.pbio.3003308
Author countries: United States
Funding: see manuscript
Journal
PLOS Biology
Method of Research
Experimental study
Subject of Research
Animals
COI Statement
Competing interests: see manuscript