Skip to main content
Article thumbnail
Location of Repository

Clinical impact of double protease inhibitor boosting with Lopinavir/Ritonavir and Amprenavir as part of salvage antiretroviral therapy

By M. Loutfy, J. Raboud, C. Thompson, A. Tseng, Z. Abdurrahman, C. Kovacs, A. Rachlis, E. Phillips, G. Rubin, K. Gough and S. Walmsley

Abstract

Purpose: Double protease inhibitor (PI) boosting is being explored as a new strategy in salvage antiretroviral (ARV) therapy. However, if a negative drug interaction leads to decreased drug levels of either or both PIs, double PI boosting could lead to decreased virologic response. A negative drug interaction has been described between amprenavir (APV) and lopinavir/ritonavir (LPV/r). This observational cohort study assessed the virologic impact of the addition of APV to a salvage ARV regimen, which also contains LPV/r, compared to a regimen containing LPV/r alone. Method: Patients initiated on a salvage ARV regimen that included LPV/r obtained from the expanded access program in Toronto, Canada, were evaluated. APV (600-1,200 mg bid) was added at the discretion of the treating physician. Results: Using multivariate Cox proportional hazards models, we found that the addition of APV to a LPV/r-containing salvage regimen was not significantly associated with time to virologic suppression (< 50 copies/mL; adjusted hazard ratio [HR] = 0.75, p = .12) or with time to virologic rebound (adjusted HR = 1.46, p = .34). Those patients who received higher doses of APV had an increased chance of virologic suppression (p = .03). In a subset of 27 patients, the median LPV Ctrough was significantly lower in patients receiving APV (p = .04), and the median APV Ctrough was reduced compared to reported controls. Conclusion: Our data do not support an additional benefit in virologic reduction of double boosting with APV and LPV/r relative to LPV/r alone in salvage ARV therapy. Our study's limitations include its retrospective nature and the imbalance between the two groups potentially confounding the results. Although these factors were adjusted for in the multivariate analysis, a prospective randomized controlled trial is warranted to confirm our findings

Publisher: Thomas Land Publishers Inc.
Year: 2003
OAI identifier: oai:researchrepository.murdoch.edu.au:16088
Provided by: Research Repository

Suggested articles

Citations

  1. (2002). A prospective study of deep salvage therapy with lopinavir/r, amprenavir, and NRTIs: final 24-week data, pharmacokinetics, and association of drug levels/drug susceptibility with virologic response. In:
  2. (2001). Amprenavir (APV) plasma concentrations are dramatically decreased by association with ABT378/r in HIV-infected patients. In:
  3. (2000). Amprenavir (APV) plasma concentrations are dramatically increased by association to ritonavir (RTV) baby-doses in HIV infected patients: possible combination with efavirenz (EFV). In:
  4. (1999). CD4 lymphocyte count as a predictor of the duration of highly active antiretroviral therapy-induced suppression of human immunodeficiency virus load. J Infect Dis.
  5. Drug interaction between amprenavir and lopinavir/ritonavir in salvage therapy [letter].
  6. (2001). Effect of reduced-dose amprenavir in combination with lopinavir on plasma levels of amprenavir in patients infected with HIV. Clin Ther.
  7. (2002). In vitro antiviral interaction of lopinavir with other protease inhibitors. Antimicrob Agents Chemother.
  8. (2001). Inhibitory quotient and efficacy of amprenavir-lopinavir containing HAART in heavily pretreated HIV infected patients. In:
  9. (2000). Meta-analysis of efficacy of triple combination therapy in antiretroviral-naive HIV-1 infected adults. In:
  10. (2002). Pharmacokinetic interaction between lopinavir/r and amprenavir in salvage therapy. In:
  11. Pharmacokinetics of amprenavir and lopinavir in combination with nevirapine in highly pretreated HIV-infected patients.
  12. (2001). Pharmacokinetics of amprenavir and lopinavir in combination with ritonavir and nevirapine in highly pretreated HIV infected patients. In:
  13. (2002). Pilot study of saquinavir-SGC (Fortovase, SQV) 1000 mg twice daily and lopinavir/ritonavir (Kaletra, LPV/r) in protease inhibitor-experienced HIV+ individuals: dose escalation and combined normalized inhibitory quotient (cNIQ). In:
  14. (2003). ritonavir with protease inhibitors in healthy volunteers. In:
  15. (2001). Salvage therapy for HIV-1 infection with lopinavir/ritonavir (LOP/RIT), saquinavir-SGC (SQR), and nucleoside analogues in patients having failed all three antiretroviral classes. In:
  16. (1998). Simultaneous quantitative determination of the HIV protease inhibitors amprenavir, indinavir, nelfinavir, ritonavir and saquinavir in human plasma by ion-pair high-performance liquid chromatography with ultraviolet detection.
  17. (2002). Switch to a simple boosted double protease inhibitor regimen of lopinavir/r and saquinavir without reverse transcriptase inhibitors after multiple therapy failures. In:
  18. Unfavourable interaction of amprenavir and lopinavir in combination with ritonavir?
  19. (2001). Unfavourable interaction of lopinavir and amprenavir in combination with ritonavir. In:
  20. (2002). Virological and immunological benefit of a salvage therapy that includes Kaletra plus Fortovase preceded or not by antiretroviral therapy interruption (TI) in advanced HIV-infected patients (6-month follow-up). In:
  21. (2002). Virological response and safety at 48 weeks of double boosted protease inhibitors with Lopinavir/R plus either Saquinavir or Amprenavir in heavily pretreated HIV infected patients. In:

To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.