PA-457 is a maturation inhibitor under development by Panacos Pharmaceuticals. Maturation inhibitors reduce HIV viral load by interfering with the production of the HIV capsid protein. If this protein is not assembled, any HIV particles that are produced are defective and unable to infect other human cells.

In a ten-day double-blind study, 33 HIV-positive patients were randomised to receive either a placebo or PA-457 at 25, 50, 100 or 200mg. On day eleven, the median viral load change at the 200mg dose was a fall of 1.03 log₁₀. In contrast, patients receiving placebo showed a median rise of 0.03 log₁₀, those taking 25mg showed a rise of 0.05 log₁₀, those taking 50mg showed a fall of 0.17 log₁₀ and those taking 100mg showed a fall of 0.48 log₁₀.

The patients starting with a viral load below 100,000 copies/ml had a median viral load reduction of 1.52 log₁₀ at the 200mg dose, while those on the 100mg dose had a median reduction of 0.56 log₁₀. Genetic analysis failed to reveal any evidence of the development of resistance to PA-457 over the course of the study.

Reference

Martin DE. The in vitro and in vivo disposition of PA-457, a novel inhibitor of HIV-1 maturation. Fifteenth International AIDS Conference, Bangkok, abstract WePeA5644, 2004.