A clinical study of the combination of 100 mg ritonavir plus 800 mg indinavir as salvage therapy: influence of increased plasma drug levels in the rate of response.
OBJECTIVE
The purpose of our study was to evaluate the efficacy of indinavir (IDV) in a twice daily dosing regimen with coadministration of 100 mg ritonavir (RTV) and to explore the influence of plasma drug levels in the rate of virologic response.


METHODS
We performed a prospective study of 59 patients who switched to a salvage regimen with two nucleoside analogs plus the combination of 100 mg RTV plus 800 mg IDV twice daily. Pharmacokinetics of IDV and RTV were assessed in 11 patients.


RESULTS
Previous antiretroviral exposure was 44 months, and 78% and 39% of patients had previously failed regimens with either IDV or RTV. Median CD4 count was 248 x 10(6)/L and HIV load was 3.9 log(10) copies/mL. The median number of mutations in the protease gene was 9 (3-14), predominantly at residues 82 (53%), 90 (42%), and 46 (32%). After 24 weeks, 61% of patients had a viral load decrease greater than 1 log(10), and 38% had a viral load below 50 copies/mL. Nephrolitiasis, hematuria, or flank pain was observed in 13 patients (22%), leading to withdrawal in six cases (10%). IDV trough levels were well above the IC(95) (median 1.75 mg/L, interquartile range 1.07-2.57), but RTV trough levels were below the IC(95) in 88% of patients. There was a close correlation between higher peak levels of IDV, virological response, and renal toxicity.


CONCLUSIONS
RTV/IDV 100/800 mg in a twice daily dosing regimen is associated with a significant virological response in patients with antiretroviral treatment failure. The correlation between plasma drug levels, toxicity, and response suggests the usefulness of individualized drug monitoring.
Casado
J L
JL
Department of Infectious Diseases, Ramon y Cajal Hospital, Madrid, Spain.
Moreno
A
A
Sabido
R
R
Martí-Belda
P
P
Antela
A
A
Dronda
F
F
Perez-Elías
M J
MJ
Moreno
S
S
D019380:Anti-HIV Agents / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D017320:HIV Protease Inhibitors / Q000493:pharmacokinetics / Q000627:therapeutic use*; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D006801:Humans; D019469:Indinavir / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011446:Prospective Studies; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use; D019438:Ritonavir / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016879:Salvage Therapy; D016896:Treatment Outcome; D019562:Viral Load
D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors; D018894:Reverse Transcriptase Inhibitors; D019469:Indinavir; D019438:Ritonavir