Antiviral activity of foscarnet in salvage patients
Mike Youle MD
Foscarnet, a pyrophosphate analogue, continues to make a minor comeback for the treatment of HIV in late stage disease (CD4 <100 cells/mm3, HIV RNA >50,000 copies/mL, 3-class drug failure). Christine Katlama presented data on a group of salvage patients in whom she used an induction regimen of 5g iv bid for 6 weeks followed by a maintenance phase, if they achieved a >1 log drop in viral load, of 5g iv bid for two days a week. 
Katlama treated 11 patients in the induction phase and 6 reached maintenance, 2 patients died of HIV disease and lymphoma, only one patients stopped due to marked oedema. Viral load decline in the induction phase ranged from -0.1 log to -2.95 log with a median of -1.79 log at week 6 and a median CD4 increase of +50 cells/mm3. Six patients started the maintenance phase but three had viral load failure whilst the other three reached >24 weeks with a CD4 rise of +71 cells/mm3 and a HIV RNA below 6,000 copies/mL. Further follow-up was curtailed by the availability of TMC114, which 7 patients commenced. Thus it appears that for extreme cases, foscarnet may be a useful tool to help patients survive until the next best agent(s) arrives in the clinic.
Thiovir is an oral foscarnet analogue being developed by Adventrx Pharmaceuticals. An in vitro study of the agent against a panel of NRTI and NNRTI resistant strains of HIV showed good activity with synergy with AZTand a 2-fold better suppression than foscarnet. After 13 rounds of replication there was a five-fold increase in IC50 to both thiovir and foscarnet, this is certainly a drug to watch out for in the future.
- Katlama C, Canestri A, Wirden M et al. Foscarnet used in salvage therapy of multidrug resistant HIV-1 infected patients. 3rd IAS Conference on HIV Pathogenesis and Treatment, Rio de Janeiro, 2005. Abstract WePe12.9C16.
- Waninger S, Ramos S, Robbins J et al. Anti-HIV-1 activity of a foscarnet analogue, synergy with zidovudine and analysis of resistance variants selected in vitro. 3rd IAS Conference on HIV Pathogenesis and Treatment, Rio de Janeiro, 2005. Abstract TuPe6.1B16.