Foscarnet salvage therapy efficacy is associated with the presence of thymidine-associated mutations (TAMs) in HIV-infected patients.

BACKGROUND

Salvage therapy based on foscarnet plus a thymidine analog is effective in patients with advanced-stage HIV disease and viruses harbouring multiple drug-resistance mutations.

OBJECTIVE

To identify viral genetic determinants associated with the virological efficacy of foscarnet salvage therapy.

STUDY

DESIGN

Thirteen patients received foscarnet at a fixed dose of 80 mg/kg twice daily for 14 days, in combination with zidovudine or stavudine.

RESULTS

The baseline median HIV viral load and CD4 cell count were 5.10log(10) copies/ml and 23 cells/mm(3), respectively. Following foscarnet therapy, viral load fell by a median of 1.84log(10)copies/ml (range: -0.29 to -2.82), and by at least 1log(10)copies/ml in 11 patients, all of whom harboured viruses with at least three thymidine-associated mutations (TAMs). The two patients with smaller declines in viral load (<0.50log(10)copies/ml) harboured viruses with only one or zero TAMs.

CONCLUSIONS

These findings corroborate, in vivo, the impact of TAMs on HIV susceptibility to foscarnet. The virological response to foscarnet salvage therapy in multiclass-experienced patients may thus differ according to the number of TAMs.