Phenylbutyrate (4-PBA) and its active metabolite, phenylacetate, have been investigated in scientific research for their ability to affect the HIV-1 virus, primarily in the context of "shock-and-kill" strategies for HIV latency reversal. While 4-PBA is an FDA-approved drug for urea cycle disorders, its role in HIV research is as an experimental agent designed to force latent (hidden) virus to become active so it can be eliminated.
Key Findings on Phenylbutyrate/Phenylacetate and HIV:
Latency Reversal Agent (LRA): Sodium phenylbutyrate functions as a histone deacetylase (HDAC) inhibitor, which can promote the transcription of HIV-1 from latency in cells.
Mechanism: It works by inhibiting enzymes that pack DNA tightly around histones, thus loosening the chromatin structure and allowing HIV to produce RNA, making the latent cells visible to the immune system.
Preclinical Findings: Studies have shown that 4-PBA can increase HIV-1 expression in latently infected cell lines.