Treatment failure of nelfinavir-containing triple therapy can largely be explained by low nelfinavir plasma concentrations

David M. Burger*, Patricia W.H. Hugen, Rob E. Aarnoutse, Richard M.W. Hoetelmans, Marielle Jambroes, Pythia T. Nieuwkerk, Gerrit Schreij, Margriet M.E. Schneider, Marchina E. Van der Ende, Joep M.A. Lange

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

64 Citations (Scopus)

Abstract

The relationship between plasma concentrations of nelfinavir and virologic treatment failure was investigated to determine the minimum effective concentration of nelfinavir. Plasma samples were prospectively collected from treatmentnaive patients who began taking nelfinavir, 1250 mg BID + two nucleoside reverse transcription inhibitors (NRTIs). Nelfinavir concentration ratios were calculated by dividing each individual nelfinavir level by the time-adjusted population value. Virologic failure was defined as either no response (a detectable viral load after 6 months) or a relapse (detectable viral load after being undetectable, of an increase in viral load >1 log above nadir). Forty-eight patients were included with a median follow-up period of 8 months. The median concentration ratio of nelfinavir was 0.98 (interquartile range, 0.76-1.47). Virologic failure was observed in 29% of the patients. In a univariate analysis, the nelfinavir concentration ratio appeared to be the single determinant that was related to virologic failure (P = 0.039). Patients with a median ratio <0.90 had a relative risk of 3.0 (95% CI, 1.2-7.6) for virologic failure. Using this threshold, virologic failures were detected with 64% sensitivity and 74% specificity (P = 0.014). Virologic failure of nelfinavir-containing triple therapy can be explained, to a large extent, by low plasma levels of nelfinavir.

Original languageEnglish
Pages (from-to)73-80
Number of pages8
JournalTherapeutic Drug Monitoring
Volume25
Issue number1
DOIs
Publication statusPublished - 1 Feb 2003

Keywords

  • Nelfinavir
  • Pharmacokinetics
  • Protease inhibitors
  • Virologic failure

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