[Antiretroviral ant anti-inflammatory properties of a novel platelet activation factor antagonist, PMS-601]

The platelet-activating factor (PAF) plays a major role in neuropathogenesis associated with human immunodeficiency virus (HIV) infection by enhancing the inflammatory syndrome and viral replication, particularly in cells of the macrophage lineage, and its neurotoxic properties. We therefore evaluated the ability of PAF-R antagonists to inhibit HIV-1 replication and down-modulate the synthesis of pro-inflammatory mediators in healthy or HIV-1-infected macrophages. PMS-601 demonstrated the highest anti-HIV activity. Considering its mode of action and anti-inflammatory properties, PMS-601 interferes with early and late steps of the HIV biological cycle and decreases the synthesis of PAF, TNF-alpha, MIP-1 alpha, MIP-1 beta and RANTES. Altogether, these results suggest that PAF-receptor antagonists, and particularly PMS-601, could be of potential value as treatment adjuvants in HIV infection.