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.


Journal Article

PURPOSE: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. METHOD: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. CONCLUSION: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.

Full Text

Cited Authors

  • Casado, JL; Moreno, A; Sabido, R; Martí-Belda, P; Antela, A; Dronda, F; Perez-Elías, MJ; Moreno, S

Published Date

  • July 2000

Published In

Volume / Issue

  • 1 / 1

Start / End Page

  • 13 - 19

PubMed ID

  • 11590485

Pubmed Central ID

  • 11590485

Electronic International Standard Serial Number (EISSN)

  • 1945-5771

International Standard Serial Number (ISSN)

  • 1528-4336

Digital Object Identifier (DOI)

  • 10.1310/hct.2000.1.1.003


  • eng