Phosphazid is an experimental anti-HIV drug being developed by Canadian and Russian researchers. It belongs to the as nucleoside analogue reverse transcriptase inhibitors, which reduce HIV in the blood by blocking HIV replication within cells.

This compound is a pro-drug of AZT (zidovudine, Retrovir), and is being developed by the Institute Biochemical Research in Moscow. As a pro-drug, it is not directly active in infected cells, needing one more activation step than AZT to become active within cells. The advantage of pro-drugs in general is that they have different absorption characteristics to the main compound: smaller doses are required to obtain the same pharmacodynamic effects in the cells, or equivalent doses may confer higher potency.

In vitro, phosphazid is reported to be tenfold more potent than AZT. Therefore, it is more difficult to select for resistant variants. Reduced sensitivity is associated with a mutation at codon D67N (Machado 1999).

After demonstrating in vitro antiretroviral activity, a dosing and safety study of phosphazid was conducted. Four doses were tested: 200mg twice daily, 200mg three times daily, 400mg twice daily and 400mg three times daily. After 12 weeks monotherapy, the 400mg doses produced mean reductions in viral load of 0.7 and 0.78 log₁₀ respectively. No major side-effects were reported, and it is described by Russian doctors as less toxic than AZT, although this has not been evaluated in a randomised study.

Phosphazid is currently marketed in Russia from 500 to 600mg daily (oral formulation), under the brand name Nicavir. For full registration in the European Union and United States, a development programme has started but so far it is only in the pre-clinical stage.

References

Machado J et al. Antiviral activity and resistance profile of phosphazid--a novel prodrug of AZT. Sixth Conference on Retroviruses and Opportunistic Infections, abstract 594, 1999.