Antiretroviral effect of foscarnet in patients with multiple drug resistance in late stage HIV disease
Simon Collins, HIV i-Base
In Volume 11, issue 5 of Antiviral Therapy, Ana Canestri and colleagues reported the results of using foscarnet as additional therapy in 11 multi-drug resistant French patients with late stage HIV disease, failing their current treatment.
Inclusion criteria for this open-label, single-arm, add-on pilot study, included viral load >50,000 copies/mL and CD4 counts <100/mm3, and documented three-class resistance. Foscarnet induction therapy consisted of 5 g intravenously twice daily for 6 weeks, in addition to their antiretroviral combination, and the primary endpoint was virological response at week 6. Patients with at least 1 log decrease in viral load at week 6 (W6), were given foscarnet 5 g intravenously twice daily on two consecutive days each week.
Median baseline CD4 and viral load were 10 cells/mm3 and at 5.16 log copies/mL respectively, with a median of 9 (RTI), 2 (NNRTI) and 12 (PI) associated mutations.
In an intent-to-treat analysis, the median change in viral load was almost -2.0 logs at week 2 and -1.79 logs at week 6. 8/11 patients had at least 1 log reduction at week 6. One patient discontinued foscarnet at week 2 because of renal toxicity.
Six patients started maintenance therapy. Change from baseline after 12 weeks of maintenance therapy was -0.85 log in the four patients who reached W12, and the median increase of CD4+ T-cell count was 60 cells/mm3.
The study noted that foscarnet markedly reduced plasma HIV load and improved immunological status. Given the toxicity associated with foscarnet, and the difficulty of administration (twice-daily IV administration, often requiring a Port-a-Cath or Hickman line for anything treatment lasting longer than a few days) this is clearly a treatment of last resort.
It may nevertheless be suitable for a limited number of patients, particularly part of a short-term strategy to maximize virological response, and particlular if they also have active CMV.
Canestri A, Ghosn J, Wirden M et al. Foscarnet as salvage therapy for patients with late-stage HIV disease and multiple drug resistance. Antiviral Therapy 2006; 11: 561-566. (Volume11, Issue 5)