The normalized inhibitory quotient of boosted protease inhibitors is predictive of viral load response in treatment-experienced HIV-1-infected individuals

Alan Winston*, Gill Hales, Janaki Amin, Erno Van Schaick, David A. Cooper, Sean Emery

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

26 Citations (Scopus)

Abstract

Objective: The normalized inhibitory quotient (NIQ) has been proposed as a measure for refining the precision of HIV resistance testing when selecting antiretroviral therapy (ART). We undertook an assessment of NIQ and 48-week virological outcome in patients commencing ritonavir-boosted protease inhibitor (PI) regimens. Design: A cohort of 87 HIV-infected individuals who all had extensive prior exposure to ART were assigned a new boosted PI regimen following resistance testing. PI therapy consisted of lopinavir, indinavir, saquinavir and amprenavir at 50, 32, 11 and 6%, respectively. Fold change (FC) for each PI was determined from the resistance test at baseline. Trough drug concentration (Cmin) was determined at week 4. Methods: NIQ was derived individually by taking the logarithm of the ratio of Cmin/FC divided by the fixed ratio of population mean trough drug concentration/clinical cut off. Associations between viral load (VL) response over 48 weeks with baseline VL, FC, Cmin, NIQ and selected PI were assessed. Results: Mean change from baseline VL reduced by 0.83 log at week 48. In multivariate analyses, baseline VL and NIQ were the parameters most associated with change from baseline VL at week 48 (P= 0.012 and 0.003, respectively). FC, Cmin and selected PI were not significantly associated with VL changes. Conclusion: In this cohort of highly treatment-experienced individuals treated with boosted PI regimens, baseline VL and NIQ were significantly predictive of virological response over 48 weeks whereas FC and Cmin were not. These results support the use of a NIQ at week 4, as a tool for predicting response to therapy in this setting.

Original languageEnglish
Pages (from-to)1393-1399
Number of pages7
JournalAIDS
Volume19
Issue number13
DOIs
Publication statusPublished - 2005
Externally publishedYes

Keywords

  • Boosted protease inhibitor therapy
  • HIV disease
  • HIV drug resistance
  • Inhibitory quotient
  • Pharmacokinetics
  • Salvage therapy

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