Efficacy of a twice-daily antiretroviral regimen containing 100 mg ritonavir/400 mg indinavir in HIV-infected patients

AIDS. 2003 Jan 24;17(2):209-14. doi: 10.1097/00002030-200301240-00011.

Abstract

Objective: To evaluate the pharmacokinetics, efficacy and tolerability of a low-dose boosted indinavir (IDV)/ritonavir (RTV) regimen [100 mg RTV/400 mg IDV twice daily (bid)] in patients previously receiving a standard IDV regimen [800 mg three times a day (tid)].

Methods: In a prospective, open-label, cross-over trial, patients with plasma HIV RNA < 200 copies/ml receiving an IDV-containing regimen (800 mg tid) were switched to an RTV/IDV (100/400 mg bid)-containing regimen. Minimal and maximal IDV plasma concentrations ( Cmin and Cmax ) were determined before the switch (day 0), at week 2 and week 4 after the switch. The CD4 cell count and plasma HIV RNA were determined at day 0, week 2 and week 4, then every 8 weeks. The primary end-point was the percentage of patients with plasma HIV RNA below 200 copies ml at week 48.

Results: Twenty patients were enrolled. At baseline, on IDV 800 mg tid, median IDV Cmin was 194 ng/ml and median IDV Cmax was 8449 ng/ml. On RTV/IDV (100/400 mg), median IDV Cmin increased to 536 ng/ml at week 2 and 475 ng/ml at week 4, while Cmax decreased to 2983 ng/ml at week 2 and 2997 ng/ml at week 4 ( P < 0.001). The median area under the IDV plasma concentration-time curve measured in seven patients was 25 126 ng.h/ml, and the IDV half-life (t1/2 ) was 4.4 h. All patients had plasma HIV RNA remaining < 200 copies/ml at week 48. Tolerability of RTV/IDV was excellent.

Conclusion: RTV/IDV (100/400 mg bid) yields significantly higher IDV plasma Cmin and lower IDV Cmax values relative to the standard IDV regimen, thereby improving both tolerability and efficacy.

Publication types

  • Clinical Trial
  • Controlled Clinical Trial

MeSH terms

  • Adult
  • CD4 Lymphocyte Count
  • Cross-Over Studies
  • Drug Administration Schedule
  • Drug Therapy, Combination
  • Female
  • HIV Infections / blood
  • HIV Infections / drug therapy*
  • HIV Infections / immunology
  • HIV Infections / virology
  • HIV Protease Inhibitors / blood
  • HIV Protease Inhibitors / therapeutic use*
  • HIV-1 / isolation & purification
  • Humans
  • Indinavir / blood
  • Indinavir / therapeutic use*
  • Male
  • Pilot Projects
  • Prospective Studies
  • RNA, Viral / blood
  • Ritonavir / blood
  • Ritonavir / therapeutic use*
  • Viral Load

Substances

  • HIV Protease Inhibitors
  • RNA, Viral
  • Indinavir
  • Ritonavir