Foscarnet salvage therapy for patients with late-stage HIV disease and multiple drug resistance.
OBJECTIVE
To evaluate the efficacy of foscarnet on HIV infection in patients with late-stage HIV disease and multiple drug resistance.


METHODS
Three drugs experienced patients with plasma viral load (pVL) > 50,000 copies/ml and CD4+ T-cell counts < 100/mm3 were eligible for this open-label, single-arm, add-on pilot study. Foscarnet induction therapy consisted of 5 g intravenously twice daily for 6 weeks, in addition to a stable antiretroviral regimen. Patients with at least 1 log10 decrease in pVL at week 6 (W6), were given foscarnet 5 g intravenously twice daily on two consecutive days each week. Primary endpoint was the virological response rate at W6.


RESULTS
Eleven patients were enrolled with a median baseline pVL at 5.16 log10 copies/ml, median CD4+ T-cell count at 10/mm3 and median number of mutations of 9, 2 and 12 associated with resistance to nucleoside reverse transcriptase inhibitors (NRTIs), non-NRTIs and protease inhibitors, respectively. One patient discontinued foscarnet at W2 because of renal toxicity. In an intent-to-treat analysis, the median change in pVL from baseline was -1.99 log10 copies/ml at W2 and -1.79 log10 copies/ml at W6. Eight out of eleven patients had a fall in pVL of at least 1 log10 at W6, and six started maintenance therapy. The median fall in pVL after 12 weeks of maintenance therapy was -0.85 log10 copies/ml in the four patients who reached W12, and the median increase of CD4+ T-cell count was 60/mm3.


CONCLUSIONS
In patients with HIV mutations conferring resistance to all antiretroviral drug classes, foscarnet markedly reduced plasma HIV load and improved immunological status.
Canestri
Ana
A
Department des Maladies Infectieuses, Hôpital Pitié-Salpétriêre, Paris, France.
Ghosn
Jade
J
Wirden
Marc
M
Marguet
Françoise
F
Ktorza
Nadine
N
Boubezari
Imane
I
Dominguez
Stéphanie
S
Bossi
Philippe
P
Caumes
Eric
E
Calvez
Vincent
V
Katlama
Christine
C
D000328:Adult; D000368:Aged; D018791:CD4 Lymphocyte Count; D018450:Disease Progression; D024921:Drug Resistance, Multiple, Viral / Q000235:genetics*; D017245:Foscarnet / Q000009:adverse effects / Q000627:therapeutic use*; D006678:HIV / Q000235:genetics*; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D017320:HIV Protease Inhibitors / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010865:Pilot Projects; D018894:Reverse Transcriptase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D016879:Salvage Therapy; D019562:Viral Load
D017320:HIV Protease Inhibitors; D018894:Reverse Transcriptase Inhibitors; D017245:Foscarnet