bevirimat

Bevirimat, also known as PA-457, is an experimental antiretroviral agent that functions as a maturation inhibitor of HIV-1. It targets the late stage of the viral life cycle by inhibiting proteolytic processing of the Gag polyprotein at the CA–SP1 junction, thereby blocking proper maturation of the virion and yielding noninfectious particles with an immature core.

Clinical development: Bevirimat advanced to phase IIb trials in combination regimens for HIV-1 infection. However, its efficacy varied among patients because several naturally occurring polymorphisms in the SP1 region of Gag reduce susceptibility to the compound in many HIV-1 strains. These polymorphisms led to reduced antiviral activity and resistance, undermining consistent clinical benefit. Consequently, development did not progress to regulatory approval, and the program was largely halted.

Pharmacology and use: Bevirimat was administered orally in trials and studied in adults. Detailed pharmacokinetic data indicated dose-proportional exposure with consideration of drug interactions, including booster agents in some regimens. Adverse events in trials were generally mild to moderate, but comprehensive safety data are limited because the compound did not advance in late-stage development.

Status: Bevirimat is not approved for clinical use and is considered an experimental compound. It served to illustrate the concept of maturation inhibitors, a field that has continued to explore alternative compounds with different resistance profiles and potency.