Salvage therapy with regimens containing ritonavir and saquinavir in extensively pretreated HIV-infected patients.
OBJECTIVE
To evaluate the efficacy and toxicity of salvage regimens containing ritonavir and saquinavir in patients failing highly active antiretroviral therapy (HAART), and to correlate outcome with plasma concentrations of protease inhibitors.


METHODS
Prospective, non-randomized interventional study.


METHODS
Thirty extensively pretreated HIV-infected patients with virological failure under HAART were treated with ritonavir (400 mg twice daily) and saquinavir (600 mg twice daily) and at least one reverse transcriptase inhibitor. HIV-RNA, CD4 cell counts and plasma concentrations of protease inhibitors were determined, and patients were monitored for toxicity at monthly intervals.


RESULTS
Six patients showed complete virological success (HIV-RNA <200 copies/ml at week 12) which was sustained for a median follow-up of 6.3 months. Partial virological response (decrease of HIV-RNA of >1 log10 at week 12) was achieved by a further three patients. Patients with a virological response had significantly higher CD4 cell increases than patients without virological response (mean increase at week 12: 66x10(6) cells/l versus 6x10(6) cells/l; P = 0.01). No clinical events were observed during 6 months of follow-up. Neither the use of a non-nucleoside reverse transcriptase inhibitor (NNRTI) nor the number of newly introduced drugs influenced the virological response. Plasma concentrations of protease inhibitors did not statistically differ between patients with and without success. Toxicity included gastrointestinal disturbances, lipid abnormalities and liver dysfunction.


CONCLUSIONS
In extensively pretreated patients, salvage regimens containing ritonavir and saquinavir had only limited and short-term anti-HIV activity and were associated with substantial toxicity. Plasma concentrations of saquinavir were not predictive for virological response.
Fätkenheuer
G
G
Department of Internal Medicine, University of Köln, Germany.
Hoetelmans
R M
RM
Hunn
N
N
Schwenk
A
A
Franzen
C
C
Reiser
M
M
Jütte
A
A
Rockstroh
J
J
Diehl
V
V
Salzberger
B
B
D000328:Adult; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D017320:HIV Protease Inhibitors / Q000097:blood / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use; D019438:Ritonavir / Q000097:blood / Q000627:therapeutic use*; D016879:Salvage Therapy; D019258:Saquinavir / Q000097:blood / Q000627:therapeutic use*; D016896:Treatment Outcome; D019562:Viral Load
D017320:HIV Protease Inhibitors; D018894:Reverse Transcriptase Inhibitors; D019258:Saquinavir; D019438:Ritonavir