A scalable ultra-long-acting tenofovir phosphonate prodrug sustains HBV suppression.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 40749058.
- Also identified by DOI 10.1126/sciadv.adw2286 and PMC identifier 12315950.
- Licence recorded as CC BY-NC.
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Abstract
Long-acting (LA) extended-release formulations are revolutionizing treatment and prevention of HIV infection. However, none of the existing LA therapies are active against hepatitis B virus (HBV), a common coinfection with HIV. Managing coinfection requires therapy to be effective against both viruses. Notable candidates are tenofovir (TFV) prodrugs. We have previously developed an LA TFV through a modified lipophilic ProTide strategy. Given the process chemistry challenges presented by amino acid chiral centers in ProTides, a simplified lipophilic amino acid-free crystalline phosphonate prodrug of TFV (M5TFV) has been created. Intramuscular injections of M5TFV nanosuspension (NM5TFV) were well tolerated in Sprague-Dawley rats and HBV transgenic mice. Notably, single doses at 200 and 400 milligrams per kilogram TFV equivalents produced >2.5 log<sub>10</sub> reduction in HBV DNA beyond 2 months in transgenic mice. Reductions of covalently closed circular DNA were seen in hepatocyte-like cells. These promising findings support further development of NM5TFV as an ultra-LA formulation.
Medical subject headings
- Prodrugs
- Tenofovir
- Hepatitis B virus
- Antiviral Agents
- Hepatitis B