Treatment Failure of Nelfinavir-Containing Triple Therapy Can Largely Be Explained by Low Nelfinavir Plasma Concentrations

Authors:
  • PHPatricia W. H. Hugen
    Patricia W. H. Hugen
  • RARob E. Aarnoutse
    Rob E. Aarnoutse
  • RHRichard M. W. Hoetelmans
    Richard M. W. Hoetelmans
  • MJMarielle Jambroes
    Marielle Jambroes
  • GSGerrit Schreij
    Gerrit Schreij
  • MSMargriet M. E. Schneider
    Margriet M. E. Schneider
  • MEMarchina E. van der Ende
    Marchina E. van der Ende
  • JLJoep M. A. Lange
    Joep M. A. Lange
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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 treatment-naive 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, or 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.

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